End Groups of Functionalized Siloxane Oligomers Direct Block-Copolymeric or Liquid-Crystalline Self-Assembly Behavior

PubMed Central

2016-01-01

Monodisperse oligodimethylsiloxanes end-functionalized with the hydrogen-bonding ureidopyrimidinone (UPy) motif undergo phase separation between their aromatic end groups and dimethylsiloxane midblocks to form ordered nanostructures with domain spacings of <5 nm. The self-assembly behavior of these well-defined oligomers resembles that of high degree of polymerization (N)–high block interaction parameter (χ) linear diblock copolymers despite their small size. Specifically, the phase morphology varies from lamellar to hexagonal to body-centered cubic with increasing asymmetry in molecular volume fraction. Mixing molecules with different molecular weights to give dispersity >1.13 results in disorder, showing importance of molecular monodispersity for ultrasmall ordered phase separation. In contrast, oligodimethylsiloxanes end-functionalized with an O-benzylated UPy derivative self-assemble into lamellar nanostructures regardless of volume fraction because of the strong preference of the end groups to aggregate in a planar geometry. Thus, these molecules display more classically liquid-crystalline self-assembly behavior where the lamellar bilayer thickness is determined by the siloxane midblock. Here the lamellar nanostructure is tolerant to molecular polydispersity. We show the importance of end groups in high χ–low N block molecules, where block-copolymer-like self-assembly in our UPy-functionalized oligodimethylsiloxanes relies upon the dominance of phase separation effects over directional end group aggregation. PMID:27054381

Influence of polysaccharides on wine protein aggregation.

PubMed

Jaeckels, Nadine; Meier, Miriam; Dietrich, Helmut; Will, Frank; Decker, Heinz; Fronk, Petra

2016-06-01

Polysaccharides are the major high-molecular weight components of wines. In contrast, proteins occur only in small amounts in wine, but contribute to haze formation. The detailed mechanism of aggregation of these proteins, especially in combination with other wine components, remains unclear. This study demonstrates the different aggregation behavior between a buffer and a model wine system by dynamic light scattering. Arabinogalactan-protein, for example, shows an increased aggregation in the model wine system, while in the buffer system a reducing effect is observed. Thus, we could show the importance to examine the behavior of wine additives under conditions close to reality, instead of simpler buffer systems. Additional experiments on melting points of wine proteins reveal that only some isoforms of thaumatin-like proteins and chitinases are involved in haze formation. We can confirm interactions between polysaccharides and proteins, but none of these polysaccharides is able to prevent haze in wine. Copyright © 2016. Published by Elsevier Ltd.

Effects of the Pathogenic Mutation A117V and the Protective Mutation H111S on the Folding and Aggregation of PrP106-126: Insights from Replica Exchange Molecular Dynamics Simulations.

PubMed

Ning, Lulu; Pan, Dabo; Zhang, Yan; Wang, Shaopeng; Liu, Huanxiang; Yao, Xiaojun

2015-01-01

The fragment 106-126 of prion protein exhibits similar properties to full-length prion. Experiments have shown that the A117V mutation enhances the aggregation of PrP106-126, while the H111S mutation abolishes the assembly. However, the mechanism of the change in the aggregation behavior of PrP106-126 upon the two mutations is not fully understood. In this study, replica exchange molecular dynamics simulations were performed to investigate the conformational ensemble of the WT PrP106-126 and its two mutants A117V and H111S. The obtained results indicate that the three species are all intrinsically disordered but they have distinct morphological differences. The A117V mutant has a higher propensity to form β-hairpin structures than the WT, while the H111S mutant has a higher population of helical structures. Furthermore, the A117V mutation increases the hydrophobic solvent accessible surface areas of PrP106-126 and the H111S mutation reduces the exposure of hydrophobic residues. It can be concluded that the difference in populations of β-hairpin structures and the change of hydrophobic solvent accessible areas may induce the different aggregation behaviors of the A117V and the H111S mutated PrP106-126. Understanding why the two mutations have contrary effects on the aggregation of PrP106-126 is very meaningful for further elucidation of the mechanism underlying aggregation and design of inhibitor against aggregation process.

Effects of the Pathogenic Mutation A117V and the Protective Mutation H111S on the Folding and Aggregation of PrP106-126: Insights from Replica Exchange Molecular Dynamics Simulations

PubMed Central

Ning, Lulu; Pan, Dabo; Zhang, Yan; Wang, Shaopeng; Liu, Huanxiang; Yao, Xiaojun

2015-01-01

The fragment 106-126 of prion protein exhibits similar properties to full-length prion. Experiments have shown that the A117V mutation enhances the aggregation of PrP106-126, while the H111S mutation abolishes the assembly. However, the mechanism of the change in the aggregation behavior of PrP106-126 upon the two mutations is not fully understood. In this study, replica exchange molecular dynamics simulations were performed to investigate the conformational ensemble of the WT PrP106-126 and its two mutants A117V and H111S. The obtained results indicate that the three species are all intrinsically disordered but they have distinct morphological differences. The A117V mutant has a higher propensity to form β-hairpin structures than the WT, while the H111S mutant has a higher population of helical structures. Furthermore, the A117V mutation increases the hydrophobic solvent accessible surface areas of PrP106-126 and the H111S mutation reduces the exposure of hydrophobic residues. It can be concluded that the difference in populations of β-hairpin structures and the change of hydrophobic solvent accessible areas may induce the different aggregation behaviors of the A117V and the H111S mutated PrP106-126. Understanding why the two mutations have contrary effects on the aggregation of PrP106-126 is very meaningful for further elucidation of the mechanism underlying aggregation and design of inhibitor against aggregation process. PMID:25993001

Mesoscale Simulation and Machine Learning of Asphaltene Aggregation Phase Behavior and Molecular Assembly Landscapes.

PubMed

Wang, Jiang; Gayatri, Mohit A; Ferguson, Andrew L

2017-05-11

Asphaltenes constitute the heaviest fraction of the aromatic group in crude oil. Aggregation and precipitation of asphaltenes during petroleum processing costs the petroleum industry billions of dollars each year due to downtime and production inefficiencies. Asphaltene aggregation proceeds via a hierarchical self-assembly process that is well-described by the Yen-Mullins model. Nevertheless, the microscopic details of the emergent cluster morphologies and their relative stability under different processing conditions remain poorly understood. We perform coarse-grained molecular dynamics simulations of a prototypical asphaltene molecule to establish a phase diagram mapping the self-assembled morphologies as a function of temperature, pressure, and n-heptane:toluene solvent ratio informing how to control asphaltene aggregation by regulating external processing conditions. We then combine our simulations with graph matching and nonlinear manifold learning to determine low-dimensional free energy surfaces governing asphaltene self-assembly. In doing so, we introduce a variant of diffusion maps designed to handle data sets with large local density variations, and report the first application of many-body diffusion maps to molecular self-assembly to recover a pseudo-1D free energy landscape. Increasing pressure only weakly affects the landscape, serving only to destabilize the largest aggregates. Increasing temperature and toluene solvent fraction stabilizes small cluster sizes and loose bonding arrangements. Although the underlying molecular mechanisms differ, the strikingly similar effect of these variables on the free energy landscape suggests that toluene acts upon asphaltene self-assembly as an effective temperature.

Kinetic control over pathway complexity in supramolecular polymerization through modulating the energy landscape by rational molecular design.

PubMed

Ogi, Soichiro; Fukui, Tomoya; Jue, Melinda L; Takeuchi, Masayuki; Sugiyasu, Kazunori

2014-12-22

Far-from-equilibrium thermodynamic systems that are established as a consequence of coupled equilibria are the origin of the complex behavior of biological systems. Therefore, research in supramolecular chemistry has recently been shifting emphasis from a thermodynamic standpoint to a kinetic one; however, control over the complex kinetic processes is still in its infancy. Herein, we report our attempt to control the time evolution of supramolecular assembly in a process in which the supramolecular assembly transforms from a J-aggregate to an H-aggregate over time. The transformation proceeds through a delicate interplay of these two aggregation pathways. We have succeeded in modulating the energy landscape of the respective aggregates by a rational molecular design. On the basis of this understanding of the energy landscape, programming of the time evolution was achieved through adjusting the balance between the coupled equilibria. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermally controlled preferential molecular aggregation state in a thiacarbocyanine dye

NASA Astrophysics Data System (ADS)

Passier, Rémy; Ritchie, James P.; Toro, Carlos; Diaz, Carlos; Masunov, Artëm E.; Belfield, Kevin D.; Hernandez, Florencio E.

2010-10-01

Herein we report the experimental and theoretical study of the temperature dependence of a thiacarbocyanine dye in its monomer, H- and J-aggregates states. We demonstrate the ability to control the ratio of monomer, H- and/or J-aggregates with heat. We link such a control to the conformation dependence of the molecule. An alternative way to gain access to the dominating species without changing the concentration as a complete switching mechanism between all the present species is proposed. The results presented in this work lead to a better understanding of thiacarbocyanine dye's behavior.

Subtle Effects of Aliphatic Alcohol Structure on Water Extraction and Solute Aggregation in Biphasic Water/ n -Dodecane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knight, Andrew W.; Qiao, Baofu; Chiarizia, Renato

Organic phase aggregation behavior of 1-octanol and its structural isomer, 2-ethylhexanol, in a biphasic n-dodecane water system is studied with a combination of physical measurement, small-angle X-ray scattering (SAXS), and atomistic molecular dynamic simulations. Physical properties of the organic phases are probed following their mixing and equilibration with immiscible water phases. Studies reveal that the interfacial tension decreases as a function of increasing alcohol concentration over the solubility range of the alcohol with no evidence for a critical aggregate concentration (cac). An uptake of water into the organic phases is quantified, as a function of alcohol content, by Karl Fischermore » titrations. The extraction of water into dodecane was further assessed as a function of alcohol concentration via the slope-analysis method sometimes employed in chemical separations. This provides a qualitative understanding of solute (water/alcohol) aggregation in the organic phase. The physical results are supported by analyses of SAXS data that reveals an emergence of aggregates in n-dodecane at elevated alcohol concentrations. The observed aggregate structure is dependent on the alcohol tail group geometry, consistent with surfactant packing parameter. The formation of these aggregates is discussed at a molecular level, where alcohol-alcohol and alcohol-water H-bonding interactions likely dominate the occurrence and morphology of the aggregates.« less

Constructing a molecular theory of self-assembly: Interplay of ideas from surfactants and block copolymers.

PubMed

Nagarajan, Ramanathan

2017-06-01

Low molecular weight surfactants and high molecular weight block copolymers display analogous self-assembly behavior in solutions and at interfaces, generating nanoscale structures of different shapes. Understanding the link between the molecular structure of these amphiphiles and their self-assembly behavior has been the goal of theoretical studies. Despite the analogies between surfactants and block copolymers, models predicting their self-assembly behavior have evolved independent of one another, each overlooking the molecular feature considered critical to the other. In this review, we focus on the interplay of ideas pertaining to surfactants and block copolymers in three areas of self-assembly. First, we show how improved free energy models have evolved by applying ideas from surfactants to block copolymers and vice versa, giving rise to a unitary theoretical framework and better predictive capabilities for both classes of amphiphiles. Second we show that even though molecular packing arguments are often used to explain aggregate shape transitions resulting from self-assembly, the molecular packing considerations are more relevant in the case of surfactants whereas free energy criteria are relevant for block copolymers. Third, we show that even though the surfactant and block copolymer aggregates are small nanostructures, the size differences between them is significant enough to make the interfacial effects control the solubilization of molecules in surfactant micelles while the bulk interactions control the solubilization in block copolymer micelles. Finally, we conclude by identifying recent theoretical progress in adapting the micelle model to a wide variety of self-assembly phenomena and the challenges to modeling posed by emerging novel classes of amphiphiles with complex biological, inorganic or nanoparticle moieties. Published by Elsevier B.V.

Effects of arginine on heat-induced aggregation of concentrated protein solutions.

PubMed

Shah, Dhawal; Shaikh, Abdul Rajjak; Peng, Xinxia; Rajagopalan, Raj

2011-01-01

Arginine is one of the commonly used additives to enhance refolding yield of proteins, to suppress aggregation of proteins, and to increase solubility of proteins, and yet the molecular interactions that contribute to the role of arginine are unclear. Here, we present experiments, using bovine serum albumin (BSA), lysozyme (LYZ), and β-lactoglobulin (BLG) as model proteins, to show that arginine can enhance heat-induced aggregation of concentrated protein solutions, contrary to the conventional belief that arginine is a universal suppressor of aggregation. Results show that the enhancement in aggregation is caused only for BSA and BLG, but not for LYZ, indicating that arginine's preferential interactions with certain residues over others could determine the effect of the additive on aggregation. We use this previously unrecognized behavior of arginine, in combination with density functional theory calculations, to identify the molecular-level interactions of arginine with various residues that determine arginine's role as an enhancer or suppressor of aggregation of proteins. The experimental and computational results suggest that the guanidinium group of arginine promotes aggregation through the hydrogen-bond-based bridging interactions with the acidic residues of a protein, whereas the binding of the guanidinium group to aromatic residues (aggregation-prone) contributes to the stability and solubilization of the proteins. The approach, we describe here, can be used to select suitable additives to stabilize a protein solution at high concentrations based on an analysis of the amino acid content of the protein. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces

PubMed Central

Dalgicdir, Cahit; Globisch, Christoph; Peter, Christine; Sayar, Mehmet

2015-01-01

Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK) and EAALAEALAEALAE (EALA), with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides’ response to macroscopic and molecular interfaces (presented by an aggregation partner) can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides’ aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity. PMID:26295346

Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces.

PubMed

Dalgicdir, Cahit; Globisch, Christoph; Peter, Christine; Sayar, Mehmet

2015-08-01

Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK) and EAALAEALAEALAE (EALA), with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides' response to macroscopic and molecular interfaces (presented by an aggregation partner) can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides' aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity.

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans.

PubMed

Jang, Heeun; Levy, Sagi; Flavell, Steven W; Mende, Fanny; Latham, Richard; Zimmer, Manuel; Bargmann, Cornelia I

2017-02-14

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9 -based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits.

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

PubMed Central

Jang, Heeun; Levy, Sagi; Flavell, Steven W.; Mende, Fanny; Latham, Richard; Zimmer, Manuel; Bargmann, Cornelia I.

2017-01-01

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans. The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9–containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9–based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits. PMID:28143932

Evolution of mixed surfactant aggregates in solutions and at solid/solution interfaces

NASA Astrophysics Data System (ADS)

Zhang, Rui

Surfactant systems have been widely used in such as enhanced oil recovery, waste treatment and metallurgy, etc., in order to solve the problem of global energy crisis, to remove the pollutants and to generate novel energy resources. Almost all surfactant systems are invariably mixtures due to beneficial and economic considerations. The sizes and shapes of aggregates in solutions and at solid/solution interfaces become important, since the nanostructures of mixed aggregates determine solution and adsorption properties. A major hurdle in science is the lack of information on the type of complexes and aggregates formed by mixtures and the lack of techniques for deriving such information. Using techniques such as analytical ultracentrifuge, small angle neutron scattering, surface tension, fluorescence, cryo-TEM, light scattering and ultrafiltration, the nanostructures of aggregates of sugar based n-dodecyl-beta-D-maltoside (DM) and nonionic pentaethyleneglycol monododecyl ether or nonyl phenol ethoxylated decyl ether (NP-10) and their mixtures have been investigated to prove the hypothesis that the aggregation behavior is linked to packing of the surfactant governed by the molecular interactions as well as the molecular structures. The results from both sedimentation velocity and sedimentation equilibrium experiments suggest coexistence of two types of micelles in nonyl phenol ethoxylated decyl ether solutions and its mixtures with n-dodecyl-beta-D-maltoside while only one micellar species is present in n-dodecyl-beta-D-maltoside solutions, in good agreement with those from small angle neutron scattering, cryo-TEM, light scattering and ultrafiltration. Type I micelles were primary micelles at cmc while type II micelles were elongated micelles. On the other hand, the nanostructures of mixed surface aggregates have been quantitatively predicted for the first time using a modified packing index. As a continuation of the Somasundaran-Fuersteneau adsorption model, a modified one-step model has been developed to fully understand the adsorption behavior of surfactant mixtures and obtained thermodynamic information on aggregation number and standard free energy for surface aggregation. The findings are expected to provide fundamental basis for the design optimal surfactant schemes for desired purposes.

Heat-Induced Soluble Protein Aggregates from Mixed Pea Globulins and β-Lactoglobulin.

PubMed

Chihi, Mohamed-Lazhar; Mession, Jean-luc; Sok, Nicolas; Saurel, Rémi

2016-04-06

The present work investigates the formation of protein aggregates (85 °C, 60 min incubation) upon heat treatment of β-lactoglobulin (βlg)-pea globulins (Glob) mixtures at pH 7.2 and 5 mM NaCl from laboratory-prepared protein isolates. Various βlg/Glob weight ratios were applied, for a total protein concentration of 2 wt % in admixture. Different analytical methods were used to determine the aggregation behavior of "mixed" aggregates, that is, surface hydrophobicity and also sulfhydryl content, protein interactions by means of SDS-PAGE electrophoresis, and molecule size distribution by DLS and gel filtration. The production of "mixed" thermal aggregates would involve both the formation of new disulfide bonds and noncovalent interactions between the denatured βlg and Glob subunits. The majority of "mixed" soluble aggregates displayed higher molecular weight and smaller diameter than those for Glob heated in isolation. The development of pea-whey protein "mixed" aggregates may help to design new ingredients for the control of innovative food textures.

Aggregation and Gelation of Aromatic Polyamides with Parallel and Anti-parallel Alignment of Molecular Dipole Along the Backbone

NASA Astrophysics Data System (ADS)

Zhu, Dan; Shang, Jing; Ye, Xiaodong; Shen, Jian

2016-12-01

The understanding of macromolecular structures and interactions is important but difficult, due to the facts that a macromolecules are of versatile conformations and aggregate states, which vary with environmental conditions and histories. In this work two polyamides with parallel or anti-parallel dipoles along the linear backbone, named as ABAB (parallel) and AABB (anti-parallel) have been studied. By using a combination of methods, the phase behaviors of the polymers during the aggregate and gelation, i.e., the forming or dissociation processes of nuclei and fibril, cluster of fibrils, and cluster-cluster aggregation have been revealed. Such abundant phase behaviors are dominated by the inter-chain interactions, including dispersion, polarity and hydrogen bonding, and correlatd with the solubility parameters of solvents, the temperature, and the polymer concentration. The results of X-ray diffraction and fast-mode dielectric relaxation indicate that AABB possesses more rigid conformation than ABAB, and because of that AABB aggregates are of long fibers while ABAB is of hairy fibril clusters, the gelation concentration in toluene is 1 w/v% for AABB, lower than the 3 w/v% for ABAB.

Confinement of Aggregation-Induced Emission Molecular Rotors in Ultrathin Two-Dimensional Porous Organic Nanosheets for Enhanced Molecular Recognition.

PubMed

Dong, Jinqiao; Li, Xu; Zhang, Kang; Di Yuan, Yi; Wang, Yuxiang; Zhai, Linzhi; Liu, Guoliang; Yuan, Daqiang; Jiang, Jianwen; Zhao, Dan

2018-03-21

Despite the rapid development of molecular rotors over the past decade, it still remains a huge challenge to understand their confined behavior in ultrathin two-dimensional (2D) nanomaterials for molecular recognition. Here, we report an all-carbon, 2D π-conjugated aromatic polymer, named NUS-25, containing flexible tetraphenylethylene (TPE) units as aggregation-induced emission (AIE) molecular rotors. NUS-25 bulk powder can be easily exfoliated into micrometer-sized lamellar freestanding nanosheets with a thickness of 2-5 nm. The dynamic behavior of the TPE rotors is partially restricted through noncovalent interactions in the ultrathin 2D nanosheets, which is proved by comparative experimental studies including AIE characteristics, size-selective molecular recognition, and theoretical calculations of rotary energy barrier. Because of the partially restricted TPE rotors, NUS-25 nanosheets are highly fluorescent. This property allows NUS-25 nanosheets to be used as a chemical sensor for the specific detection of acenaphthylene among a series of polycyclic aromatic hydrocarbons (PAHs) via fluorescent quenching mechanism. Further investigations show that NUS-25 nanosheets have much higher sensitivity and selectivity than their stacked bulk powder and other similar polymers containing dynamic TPE rotors. The highly efficient molecular recognition can be attributed to the photoinduced electron transfer (PET) from NUS-25 nanosheets to acenaphthylene, which is investigated by time-resolved photoluminescence measurements (TRPL), excitation and emission spectra, and density functional theory (DFT) calculations. Our findings demonstrate that confinement of AIE molecular rotors in 2D nanomaterials can enhance the molecular recognition. We anticipate that the material design strategy demonstrated in this study will inspire the development of other ultrathin 2D nanomaterials equipped with smart molecular machines for various applications.

Aggregation behavior of sodium lauryl ether sulfate with a positively bicharged organic salt and effects of the mixture on fluorescent properties of conjugated polyelectrolytes.

PubMed

Tang, Yongqiang; Liu, Zhang; Zhu, Linyi; Han, Yuchun; Wang, Yilin

2015-02-24

The aggregation behavior of anionic single-chain surfactant sodium lauryl ether sulfate containing three ether groups (SLE3S) with positively bicharged organic salt 1,2-bis(2-benzylammoniumethoxy)ethane dichloride (BEO) has been investigated in aqueous solution, and the effects of the BEO/SLE3S aggregate transitions on the fluorescent properties of anionic conjugated polyelectrolyte MPS-PPV with a larger molecular weight and cationic conjugated oligoelectrolyte DAB have been evaluated. Without BEO, SLE3S does not affect the fluorescent properties of MPS-PPV and only affects the fluorescent properties of DAB at a higher SLE3S concentration. With the addition of BEO, SLE3S and BEO form gemini-like surfactant (SLE3S)2-BEO. When the BEO/SLE3S molar ratio is fixed at 0.25, with increasing the BEO/SLE3S concentration, the BEO/SLE3S mixture forms large, loosely arranged aggregates and then transforms to closely packed spherical aggregates and finally to long thread-like micelles. The photoluminescence (PL) intensity of MPS-PPV varies with the morphologies of the BEO/SLE3S aggregates, while the PL intensity of DAB is almost independent of the aggregate morphologies. The results demonstrate that gemini-like surfactants formed through intermolecular interactions can effectively adjust the fluorescent properties of conjugated polyelectrolytes.

Identifying the Assembly Configuration and Fluorescence Spectra of Nanoscale Zinc-Tetraphenylporphyrin Aggregates with Scanning Tunneling Microscopy

PubMed Central

Zhang, Xiao-Lei; Jiang, Jian-Wei; Liu, Yi-Ting; Lou, Shi-Tao; Gao, Chun-Lei; Jin, Qing-Yuan

2016-01-01

ZnTPP (Zinc-Tetraphenylporphyrin) is one of the most common nanostructured materials, having high stability and excellent optoelectronic properties. In this paper, the fluorescence features of self-assembled ZnTPP monomers and aggregates on Au(111) surface are investigated in detail on the nanometer scale with scanning tunneling microscopy (STM). The formation of ZnTPP dimers is found in thick layers of a layer-by-layer molecular assembly on Au substrate with its specific molecular arrangement well characterized. Tip-induced luminescence shows a red shift from tilted dimers comparing with the behavior from monomers, which can be attributed to the change of vibrational states due to the intermolecular interaction and the increasing dielectric effect. The nanoscale configuration dependence of electroluminescence is demonstrated to provide a powerful tool aiding the design of functional molecular photoelectric devices. PMID:26948654

Solubilization of aromatic and hydrophobic moieties by arginine in aqueous solutions

NASA Astrophysics Data System (ADS)

Li, Jianguo; Garg, Manju; Shah, Dhawal; Rajagopalan, Raj

2010-08-01

Experiments hold intriguing, circumstantial clues to the mechanisms behind arginine-mediated solubilization of small organic drugs and suppression of protein aggregation driven by hydrophobic or aromatic associations, but how exactly arginine's molecular structure and interactions contribute to its function remains unclear since attention has focused so far on the thermodynamics of the preferential exclusion or binding of arginine. Here, we examine, through molecular dynamics simulations, how arginine solubilizes nanoscale particles with hydrophobic surfaces or aromatic-ring-type surface interactions. We show that preferential, hydrophobic, and dispersion interactions of arginine's guanidinium group with the particles lead to a surfactant-like behavior of arginine around the particles and to a solvation layer with a protective polar mask creating a hydrophilic shell. Additionally, arginine-arginine association around the solvation layer further prevents aggregative contacts. The results shed some light on the mechanistic basis of arginine's function as a suppressant of protein aggregation, although the complex energy landscapes and kinetic pathways of aggregation are protein-dependent and pose formidable challenges to developing comprehensive mechanistic pictures. Our results suggest arginine's mode of interaction with hydrophobic patches and aromatic residues could reduce aggregation-prone intermediate states of proteins and shield protein-protein aggregative contacts. The approach used here offers a systematic way of exploring implications of other amino acid/excipient interactions by studying interactions of the excipient with particles grafted with amino acids.

Designed synthesis and supramolecular architectures of furan-substituted perylene diimide.

PubMed

Yu, Yanwen; Li, Yongjun; Qin, Zhihong; Jiang, Runsheng; Liu, Huibiao; Li, Yuliang

2013-06-01

Novel furan-substituted perylene diimides are successfully synthesized and an efficient supramolecular architecture approach to construct zero/one-dimensional nano- and micro-structures by controlling solvents has been demonstrated. The aggregate structure conversion in different molecular structures can be controlled in the form of sphere-like, rod-like, and vesicle-like structures. As expected, these solid supramolecular rod-like architectures displayed interesting optical waveguide behavior, which indicates the aggregate structure materials of furan-substituted perylene diimides have the potential application as micro-scale photonic elements. Copyright © 2013 Elsevier Inc. All rights reserved.

Study of the aggregation mechanism of polyglutamine peptides using replica exchange molecular dynamics simulations.

PubMed

Nakano, Miki; Ebina, Kuniyoshi; Tanaka, Shigenori

2013-04-01

Polyglutamine (polyQ, a peptide) with an abnormal repeat length is the causative agent of polyQ diseases, such as Huntington's disease. Although glutamine is a polar residue, polyQ peptides form insoluble aggregates in water, and the mechanism for this aggregation is still unclear. To elucidate the detailed mechanism for the nucleation and aggregation of polyQ peptides, replica exchange molecular dynamics simulations were performed for monomers and dimers of polyQ peptides with several chain lengths. Furthermore, to determine how the aggregation mechanism of polyQ differs from those of other peptides, we compared the results for polyQ with those of polyasparagine and polyleucine. The energy barrier between the monomeric and dimeric states of polyQ was found to be relatively low, and it was observed that polyQ dimers strongly favor the formation of antiparallel β-sheet structures. We also found a characteristic behavior of the monomeric polyQ peptide: a turn at the eighth residue is always present, even when the chain length is varied. We previously showed that a structure including more than two sets of β-turns is stable, so a long monomeric polyQ chain can act as an aggregation nucleus by forming several pairs of antiparallel β-sheet structures within a single chain. Since the aggregation of polyQ peptides has some features in common with an amyloid fibril, our results shed light on the mechanism for the aggregation of polyQ peptides as well as the mechanism for the formation of general amyloid fibrils, which cause the onset of amyloid diseases.

Temperature Effect on Micelle Formation: Molecular Thermodynamic Model Revisited.

PubMed

Khoshnood, Atefeh; Lukanov, Boris; Firoozabadi, Abbas

2016-03-08

Temperature affects the aggregation of macromolecules such as surfactants, polymers, and proteins in aqueous solutions. The effect on the critical micelle concentration (CMC) is often nonmonotonic. In this work, the effect of temperature on the micellization of ionic and nonionic surfactants in aqueous solutions is studied using a molecular thermodynamic model. Previous studies based on this technique have predicted monotonic behavior for ionic surfactants. Our investigation shows that the choice of tail transfer energy to describe the hydrophobic effect between the surfactant tails and the polar solvent molecules plays a key role in the predicted CMC. We modify the tail transfer energy by taking into account the effect of the surfactant head on the neighboring methylene group. The modification improves the description of the CMC and the predicted micellar size for aqueous solutions of sodium n-alkyl sulfate, dodecyl trimethylammonium bromide (DTAB), and n-alkyl polyoxyethylene. The new tail transfer energy describes the nonmonotonic behavior of CMC versus temperature. In the DTAB-water system, we redefine the head size by including the methylene group, next to the nitrogen, in the head. The change in the head size along with our modified tail transfer energy improves the CMC and aggregation size prediction significantly. Tail transfer is a dominant energy contribution in micellar and microemulsion systems. It also promotes the adsorption of surfactants at fluid-fluid interfaces and affects the formation of adsorbed layer at fluid-solid interfaces. Our proposed modifications have direct applications in the thermodynamic modeling of the effect of temperature on molecular aggregation, both in the bulk and at the interfaces.

Characterization, origin and aggregation behavior of colloids in eutrophic shallow lake.

PubMed

Xu, Huacheng; Xu, Mengwen; Li, Yani; Liu, Xin; Guo, Laodong; Jiang, Helong

2018-05-31

Stability of colloidal particles contributes to the turbidity in the water column, which significantly influences water quality and ecological functions in aquatic environments especially shallow lakes. Here we report characterization, origin and aggregation behavior of aquatic colloids, including natural colloidal particles (NCPs) and total inorganic colloidal particles (TICPs), in a highly turbid shallow lake, via field observations, simulation experiments, ultrafiltration, spectral and microscopic, and light scattering techniques. The colloidal particles were characterized with various shapes (spherical, polygonal and elliptical) and aluminum-, silicon-, and ferric-containing mineralogical structures, with a size range of 20-200 nm. The process of sediment re-suspension under environmentally relevant conditions contributed 78-80% of TICPs and 54-55% of NCPs in Lake Taihu, representing an important source of colloids in the water column. Both mono- and divalent electrolytes enhanced colloidal aggregation, while a reverse trend was observed in the presence of natural organic matter (NOM). The influence of NOM on colloidal stability was highly related to molecular weight (MW) properties with the high MW fraction exhibiting higher stability efficiency than the low MW counterparts. However, the MW-dependent aggregation behavior for NCPs was less significant than that for TICPs, implying that previous results on colloidal behavior using model inorganic colloids alone should be reevaluated. Further studies are needed to better understand the mobility/stability and transformation of aquatic colloids and their role in governing the fate and transport of pollutants in natural waters. Copyright © 2018. Published by Elsevier Ltd.

Aggregation of Carbocyanine Dyes in Choline Chloride-Based Deep Eutectic Solvents in the Presence of an Aqueous Base.

PubMed

Pal, Mahi; Yadav, Anita; Pandey, Siddharth

2017-09-26

Deep eutectic solvents (DESs) have shown potential as novel media to support molecular aggregation. The self-aggregation behavior of two common and popular carbocyanine dyes, 5,5',6,6'-tetrachloro-1,1'-diethyl-3,3'-di(4-sulfobutyl)-benzimidazole carbocyanine (TDBC) and 5,5'-dichloro-3,3'-di(3-sulfopropyl)-9-methyl-benzothiacarbo cyanine (DMTC), is investigated within DES-based systems under ambient conditions. Although TDBC is known to form J-aggregates in basic aqueous solution, DMTC forms H-aggregates under similar conditions. The DESs used, glyceline and reline, are composed of salt choline chloride and two vastly different H-bond donors, glycerol and urea, respectively, in 1:2 mol ratios. Both DESs in the presence of base are found to support J-aggregates of TDBC. These fluorescent J-aggregates are characterized by small Stokes' shifts and subnanosecond fluorescence lifetimes. Under similar conditions, DMTC forms fluorescent H-aggregates along with J-aggregates within the two DES-based systems. The addition of cationic surfactant cetyltrimethylammonium bromide (CTAB) below its critical micelle concentration (cmc) to a TDBC solution of aqueous base-added glyceline shows the prominent presence of J-aggregates, and increasing the CTAB concentration to above cmc results in the disruption of J-aggregates and the formation of unprecedented H-aggregates. DMTC exclusively forms H-aggregates within a CTAB solution of aqueous base-added glyceline irrespective of the surfactant concentration. Anionic surfactant, sodium dodecylsulfate (SDS), present below its cmc within aqueous base-added DESs supports J-aggregation by TDBC; for similar SDS addition, DMTC forms H-aggregates within the glyceline-based system whereas both H- and J-aggregates exist within the reline-based system. A comparison of the carbocyanine dye behavior in various aqueous base-added DES systems to that in aqueous basic media reveals contrasting aggregation tendencies and/or efficiencies. Surfactants as additives are demonstrated to control and modulate carbocyanine dye self-aggregation within DES-based media. The unique nature of DESs as alternate media toward affecting cyanine dye aggregation is highlighted.

A MD simulation and analysis for aggregation behaviors of nanoscale zero-valent iron particles in water via MS.

PubMed

Zhao, Ying; Liu, Dongmei; Tang, Huan; Lu, Jing; Cui, Fuyi

2014-01-01

With the development of nanotechnology, more nanomaterials will enter into water environment system. Studying the existing form of nanomaterials in water environment will help people benefit from the correct use of them and to reduce the harm to human caused by them for some nanomaterials can bring polluting effect. Aggregation is a main behavior for nanoparticle in water environment. NZVI are used widely in many fields resulting in more NZVI in water environment. Molecular dynamics simulations and Materials Studio software are used to investigate the microaggregation behaviors of NZVI particles. Two scenes are involved: (1) particle size of NZVI in each simulation system is the same, but initial distance of two NZVI particles is different; (2) initial distance of two NZVI particles in each simulation system is the same, but particle size of NZVI is different. Atomistic trajectory, NP activity, total energy, and adsorption of H2O are analyzed with MS. The method provides new quantitative insight into the structure, energy, and dynamics of the aggregation behaviors of NZVI particles in water. It is necessary to understand microchange of NPs in water because it can provide theoretical research that is used to reduce polluting effect of NPs on water environment.

A MD Simulation and Analysis for Aggregation Behaviors of Nanoscale Zero-Valent Iron Particles in Water via MS

PubMed Central

Liu, Dongmei; Tang, Huan; Lu, Jing; Cui, Fuyi

2014-01-01

With the development of nanotechnology, more nanomaterials will enter into water environment system. Studying the existing form of nanomaterials in water environment will help people benefit from the correct use of them and to reduce the harm to human caused by them for some nanomaterials can bring polluting effect. Aggregation is a main behavior for nanoparticle in water environment. NZVI are used widely in many fields resulting in more NZVI in water environment. Molecular dynamics simulations and Materials Studio software are used to investigate the microaggregation behaviors of NZVI particles. Two scenes are involved: (1) particle size of NZVI in each simulation system is the same, but initial distance of two NZVI particles is different; (2) initial distance of two NZVI particles in each simulation system is the same, but particle size of NZVI is different. Atomistic trajectory, NP activity, total energy, and adsorption of H2O are analyzed with MS. The method provides new quantitative insight into the structure, energy, and dynamics of the aggregation behaviors of NZVI particles in water. It is necessary to understand microchange of NPs in water because it can provide theoretical research that is used to reduce polluting effect of NPs on water environment. PMID:25250388

Sequence Directionality Dramatically Affects LCST Behavior of Elastin-Like Polypeptides.

PubMed

Li, Nan K; Roberts, Stefan; Quiroz, Felipe Garcia; Chilkoti, Ashutosh; Yingling, Yaroslava G

2018-04-30

Elastin-like polypeptides (ELP) exhibit an inverse temperature transition or lower critical solution temperature (LCST) transition phase behavior in aqueous solutions. In this paper, the thermal responsive properties of the canonical ELP, poly(VPGVG), and its reverse sequence poly(VGPVG) were investigated by turbidity measurements of the cloud point behavior, circular dichroism (CD) measurements, and all-atom molecular dynamics (MD) simulations to gain a molecular understanding of mechanism that controls hysteretic phase behavior. It was shown experimentally that both poly(VPGVG) and poly(VGPVG) undergo a transition from soluble to insoluble in aqueous solution upon heating above the transition temperature ( T t ). However, poly(VPGVG) resolubilizes upon cooling below its T t , whereas the reverse sequence, poly(VGPVG), remains aggregated despite significant undercooling below the T t . The results from MD simulations indicated that a change in sequence order results in significant differences in the dynamics of the specific residues, especially valines, which lead to extensive changes in the conformations of VPGVG and VGPVG pentamers and, consequently, dissimilar propensities for secondary structure formation and overall structure of polypeptides. These changes affected the relative hydrophilicities of polypeptides above T t , where poly(VGPVG) is more hydrophilic than poly(VPGVG) with more extended conformation and larger surface area, which led to formation of strong interchain hydrogen bonds responsible for stabilization of the aggregated phase and the observed thermal hysteresis for poly(VGPVG).

Prediction of the aggregation propensity of proteins from the primary sequence: aggregation properties of proteomes.

PubMed

Castillo, Virginia; Graña-Montes, Ricardo; Sabate, Raimon; Ventura, Salvador

2011-06-01

In the cell, protein folding into stable globular conformations is in competition with aggregation into non-functional and usually toxic structures, since the biophysical properties that promote folding also tend to favor intermolecular contacts, leading to the formation of β-sheet-enriched insoluble assemblies. The formation of protein deposits is linked to at least 20 different human disorders, ranging from dementia to diabetes. Furthermore, protein deposition inside cells represents a major obstacle for the biotechnological production of polypeptides. Importantly, the aggregation behavior of polypeptides appears to be strongly influenced by the intrinsic properties encoded in their sequences and specifically by the presence of selective short regions with high aggregation propensity. This allows computational methods to be used to analyze the aggregation properties of proteins without the previous requirement for structural information. Applications range from the identification of individual amyloidogenic regions in disease-linked polypeptides to the analysis of the aggregation properties of complete proteomes. Herein, we review these theoretical approaches and illustrate how they have become important and useful tools in understanding the molecular mechanisms underlying protein aggregation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Environmentally-relevant concentrations of Al(III) and Fe(III) cations induce aggregation of free DNA by complexation with phosphate group.

PubMed

Qin, Chao; Kang, Fuxing; Zhang, Wei; Shou, Weijun; Hu, Xiaojie; Gao, Yanzheng

2017-10-15

Environmental persistence of free DNA is influenced by its complexation with other chemical species and its aggregation mechanisms. However, it is not well-known how naturally-abundant metal ions, e.g., Al(III) and Fe(III), influence DNA aggregation. This study investigated aggregation behaviors of model DNA from salmon testes as influenced by metal cations, and elucidated the predominant mechanism responsible for DNA aggregation. Compared to monovalent (K + and Na + ) and divalent (Ca 2+ and Mg 2+ ) cations, Al(III) and Fe(III) species in aqueous solution caused rapid DNA aggregations. The maximal DNA aggregation occurred at 0.05 mmol/L Al(III) or 0.075 mmol/L Fe(III), respectively. A combination of atomic force microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy revealed that Al(III) and Fe(III) complexed with negatively charged phosphate groups to neutralize DNA charges, resulting in decreased electrostatic repulsion and subsequent DNA aggregation. Zeta potential measurements and molecular computation further support this mechanism. Furthermore, DNA aggregation was enhanced at higher temperature and near neutral pH. Therefore, DNA aggregation is collectively determined by many environmental factors such as ion species, temperature, and solution pH. Copyright © 2017 Elsevier Ltd. All rights reserved.

Flocculation of colloidal clay by bacterial polysaccharides: effect of macromolecule charge and structure.

PubMed

Labille, J; Thomas, F; Milas, M; Vanhaverbeke, C

2005-04-01

The molecular mechanism of montmorillonite flocculation by bacterial polysaccharides was investigated, with special emphasis on the effect of carboxylic charges in the macromolecules on the mechanisms of interaction with the clay surface. An indirect way to quantify the energy of interaction was used, by comparing the flocculation ability of variously acidic polysaccharides. Data on tensile strength of aggregates in diluted suspension were collected by timed size measurements in the domain 0.1-600 microm, using laser diffraction. The flow behavior of settled aggregates was studied by rheology measurements. Flocculation of colloidal clay suspension by polysaccharides requires cancelling of the electrostatic repulsions by salts, which allows approach of clay surfaces close enough to be bridged by adsorbing macromolecules. The amount of acidic charges of the polysaccharides, and especially their location in the molecular structure, governs the bridging mechanism and the resulting tensile strength of the aggregates. The exposure of carboxylate groups located on side chains strongly promotes flocculation. In turn, charges located on the backbone of the polysaccharide are less accessible to interaction, and the flocculation ability of such polysaccharides is lowered. Measurements at different pH indicate that adsorption of acidic polysaccharides occurs via electrostatic interactions on the amphoteric edge surface of clay platelets, whereas neutral polysaccharides rather adsorb via weak interactions. Increased tensile strength in diluted aggregates due to strong surface interactions results in proportionally increased viscosity of the concentrated aggregates.

Molecular Origins of Thermal Transitions in Polyelectrolyte Assemblies

NASA Astrophysics Data System (ADS)

Yildirim, Erol; Zhang, Yanpu; Antila, Hanne S.; Lutkenhaus, Jodie L.; Sammalkorpi, Maria; Aalto Team; Texas A&M Team

2015-03-01

Polyelectrolyte (PE) multilayers and complexes formed from oppositely charged polymers can exhibit extraordinary superhydrophobicity, mechanical strength and responsiveness resulting in applications ranging functional membranes, optics, sensors and drug delivery. Depending on the assembly conditions, PE assemblies may undergo a thermal transition from glassy to soft behavior under heating. Our earlier work using thermal analysis measurements shows a distinct thermal transition for PE layer-by-layer (LbL) systems assembled with added salt but no analogous transition in films assembled without added salt or dry systems. These findings raise interesting questions on the nature of the thermal transition; here, we explore its molecular origins through characterization of the PE aggregates by temperature-controlled all-atom molecular dynamics simulations. We show via molecular simulations the thermal transition results from the existence of an LCST (lower critical solution temperature) in the PE systems: the diffusion behavior, hydrogen bond formation, and bridging capacity of water molecules plasticizing the complex changes at the transition temperature. We quantify the behavior, map its chemistry specificity through comparison of strongly and weakly charged PE complexes, and connect the findings to our interrelated QCM-D experiments.

Morphological study on small molecule acceptor-based organic solar cells with efficiencies beyond 7% (Presentation Recording)

NASA Astrophysics Data System (ADS)

Ma, Wei; Yan, He

2015-10-01

Despite the essential role of fullerenes in achieving best-performance organic solar cells (OSCs), fullerene acceptors have several drawbacks including poor light absorption, high-cost production and purification. For this reason, small molecule acceptor (SMA)-based OSCs have attracted much attention due to the easy tunability of electronic and optical properties of SMA materials. In this study, polymers with temperature dependent aggregation behaviors are combined with various small molecule acceptor materials, which lead to impressive power conversion efficiencies of up to 7.3%. The morphological and aggregation properties of the polymer:small molecule blends are studied in details. It is found that the temperature-dependent aggregation behavior of polymers allows for the processing of the polymer solutions at moderately elevated temperature, and more importantly, controlled aggregation and strong crystallization of the polymer during the film cooling and drying process. This results in a well-controlled and near-ideal polymer:small molecule morphology that is controlled by polymer aggregation during warm casting and thus insensitive to the choice of small molecules. As a result, several cases of highly efficient (PCE between 6-7.3%) SMA OSCs are achieved. The second part of this presentation will describe the morphology of a new small molecule acceptor with a unique 3D structure. The relationship between molecular structure and morphology is revealed.

Structure and dynamics in self-organized C60 fullerenes.

PubMed

Patnaik, Archita

2007-01-01

This manuscript on 'structure and dynamics in self-organized C60 fullerenes' has three sections dealing with: (A) pristine C60 aggregate structure and geometry in solvents of varying dielectric constant. Here, using positronium (Ps) as a fundamental probe which maps changes in the local electron density of the microenvironment, the onset concentration for stable C60 aggregate formation and its phase behavior is deduced from the specific interactions of the Ps atom with the surrounding. (B) A novel methanofullerene dyad, based on a hydrophobic (acceptor C60 moiety)-hydrophilic (bridge with benzene and ester functionalities)-hydrophobic (donor didodecyloxybenzene) network is chosen for investigation of characteristic self-assembly it undergoes leading to supramolecular aggregates. The pi-electronic amphiphile, necessitating a critical dielectric constant epsilon > or = 30 in binary THF-water mixtures, dictated the formation of bilayer vesicles as precursors for spherical fractal aggregates upon complete dyad extraction into a more polar water phase. (C) While the molecular orientation is dependent on the packing density, the ordering of the molecular arrangement, indispensable for self-assembly depends on the balance between the structures demanded by inter-molecular and molecule-substrate interactions. The molecular orientation in a monolayer affects the orientation in a multilayer, formed on the monolayer, suggesting the possibility of the latter to act as a template for controlling the structure of the three dimensionally grown self-assembled molecular aggregation. A systematic study on the electronic structure and orientation associated with C60 functionalized aminothiol self-assembled monolayers on Au(111) surface is presented using surface sensitive Ultra-Violet Photoelectron Spectroscopy (UPS) and C-K edge Near-Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy. The results revealed drastic modifications to d-band structure of Au(111) and the electronic structure was found sensitive towards the S-Au interface and the C60 end functional moiety with formation of localized sigma-(S-Au) and sigma(N-C) bonds, respectively. Upon binding C60 to the amine-terminated alkanethiol SAM, a drastically reduced HOMO-LUMO gap of 2.7 eV as compared to a large electronic gap of approximately 8 eV in alkanethiols enables the SAM to be a potential electron transport medium.

Chiral J-aggregates of atropo-enantiomeric perylene bisimides and their self-sorting behavior.

PubMed

Xie, Zengqi; Stepanenko, Vladimir; Radacki, Krzysztof; Würthner, Frank

2012-06-04

Herein we report on structural, morphological, and optical properties of homochiral and heterochiral J-aggregates that were created by nucleation-elongation assembly of atropo-enantiomerically pure and racemic perylene bisimides (PBIs), respectively. Our detailed studies with conformationally stable biphenoxy-bridged chiral PBIs by UV/Vis absorption, circular dichroism (CD) spectroscopy, and atomic force microscopy (AFM) revealed structurally as well as spectroscopically quite different kinds of J-aggregates for enantiomerically pure and racemic PBIs. AFM investigations showed that enantiopure PBIs form helical nanowires of unique diameter and large length-to-width ratio by self-recognition, while racemic PBIs provide irregular-sized particles by self-discrimination of the enantiomers at the stage of nucleation. Steady-state fluorescence spectroscopy studies revealed that the photoluminescence efficiency of homochiral J-aggregated nanowires (47±3%) is significantly higher than that of heterochiral J-aggregated particle-like aggregates (12±3%), which is explained in terms of highly ordered molecular stacking in one-dimensional nanowires of homochiral J-aggregates. Our present results demonstrate the high impact of homochirality on the construction of well-defined nanostructures with unique optical properties. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strong coupling-like phenomenon in single metallic nanoparticle embedded in molecular J-aggregates

NASA Astrophysics Data System (ADS)

Feng, Xin; Wang, Chen; Ma, Hongjing; Chen, Yuanyuan; Duan, Gaoyan; Zhang, Pengfei; Song, Gang

2018-02-01

Strong coupling-like phenomenon between plasmonic cavities and emitters provides a new way to realize the quantum-like effect controlling at microscale/nanoscale. We investigate the strong coupling-like phenomenon in the structure of single metallic nanoparticle embedded in molecular J-aggregates by the classical simulation method and show that the size of the metallic nanoparticle and the oscillator strength of molecular J-aggregates impact the strong coupling-like phenomenon. The strong coupling-like phenomenon is induced by the interactions between two dipoles formed by the metallic nanoparticle and molecular J-aggregates or the interactions between the dipole generated from molecular J-aggregates and the quadrupole generated from the metallic nanoparticle. The strong coupling-like phenomenon appears evidently with the increase in oscillator strength of molecular J-aggregates. The detuning energy linearly decreases with the increase in radius of the metallic nanoparticle. Our structure has potential applications in quantum networks, quantum key distributions and so on.

[Results of Simulation Studies

NASA Technical Reports Server (NTRS)

2003-01-01

Lattice Monte Carlo and off-lattice molecular dynamics simulations of h(sub 1)t(sub 4) and h(sub 4)t(sub l) (head/tail) amphiphile solutions have been performed as a function of surfactant concentration and temperature. The lattice and off-lattice systems exhibit quite different self-assembly behavior at equivalent thermodynamic conditions. We found that in the weakly aggregating regime (no preferred-size micelles), all models yield similar micelle size distributions at the same average aggregation number, albeit at different thermodynamic conditions (temperatures). In the strongly aggregating regime, this mapping between models (through temperature adjustment) fails, and the models exhibit qualitatively different micellization behavior. Incipient micellization in a model self-associating telechelic polymer solution results in a network with a transient elastic response that decays by a two-step relaxation: the first is due to a heterogeneous jump-diffusion process involving entrapment of end-groups within well-defined clusters and this is followed by rapid diffusion to neighboring clusters and a decay (terminal relaxation) due to cluster disintegration. The viscoelastic response of the solution manifests characteristics of a glass transition and entangled polymer network.

Computer Simulation of Fracture in Aerogels

NASA Technical Reports Server (NTRS)

Good, Brian S.

2006-01-01

Aerogels are of interest to the aerospace community primarily for their thermal properties, notably their low thermal conductivities. While the gels are typically fragile, recent advances in the application of conformal polymer layers to these gels has made them potentially useful as lightweight structural materials as well. In this work, we investigate the strength and fracture behavior of silica aerogels using a molecular statics-based computer simulation technique. The gels' structure is simulated via a Diffusion Limited Cluster Aggregation (DLCA) algorithm, which produces fractal structures representing experimentally observed aggregates of so-called secondary particles, themselves composed of amorphous silica primary particles an order of magnitude smaller. We have performed multi-length-scale simulations of fracture in silica aerogels, in which the interaction b e e n two secondary particles is assumed to be described by a Morse pair potential parameterized such that the potential range is much smaller than the secondary particle size. These Morse parameters are obtained by atomistic simulation of models of the experimentally-observed amorphous silica "bridges," with the fracture behavior of these bridges modeled via molecular statics using a Morse/Coulomb potential for silica. We consider the energetics of the fracture, and compare qualitative features of low-and high-density gel fracture.

A Simulated Intermediate State for Folding and Aggregation Provides Insights into ΔN6 β2-Microglobulin Amyloidogenic Behavior

PubMed Central

Estácio, Sílvia G.; Krobath, Heinrich; Vila-Viçosa, Diogo; Machuqueiro, Miguel; Shakhnovich, Eugene I.; Faísca, Patrícia F. N.

2014-01-01

A major component of ex vivo amyloid plaques of patients with dialysis-related amyloidosis (DRA) is a cleaved variant of β2-microglobulin (ΔN6) lacking the first six N-terminal residues. Here we perform a computational study on ΔN6, which provides clues to understand the amyloidogenicity of the full-length β2-microglobulin. Contrary to the wild-type form, ΔN6 is able to efficiently nucleate fibrillogenesis in vitro at physiological pH. This behavior is enhanced by a mild acidification of the medium such as that occurring in the synovial fluid of DRA patients. Results reported in this work, based on molecular simulations, indicate that deletion of the N-terminal hexapeptide triggers the formation of an intermediate state for folding and aggregation with an unstructured strand A and a native-like core. Strand A plays a pivotal role in aggregation by acting as a sticky hook in dimer assembly. This study further predicts that the detachment of strand A from the core is maximized at pH 6.2 resulting into higher aggregation efficiency. The structural mapping of the dimerization interface suggests that Tyr10, His13, Phe30 and His84 are hot-spot residues in ΔN6 amyloidogenesis. PMID:24809460

Nanoarchitectonics of molecular aggregates: science and technology.

PubMed

Ramanathan, Muruganathan; Hong, Kunlun; Ji, Qingmin; Yonamine, Yusuke; Hill, Jonathan P; Ariga, Katsuhiko

2014-01-01

The field of making, studying and using molecular aggregates, in which the individual molecules (monomers) are arranged in a regular fashion, has come a long way. Taking control over the aggregation of small molecules and polymers in bulk, on surfaces and at interfaces pose a considerable challenge for their utilization in modern high tech applications. In this review, we provide a detailed insight into recent trends in molecular aggregates from the perspectives of nanoarchitectonics.

Nanoarchitectonics of Molecular Aggregates: Science and Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramanathan, Nathan Muruganathan; Hong, Kunlun; Ji, Dr. Qingmin

2014-01-01

The field of making, studying and using molecular aggregates, in which the individual molecules (monomers) are arranged in a regular fashion, has come a long way. Taking control over the aggregation of small molecules and polymers in bulk, on surfaces and at interfaces pose a considerable challenge for their utilization in modern high tech applications. In this review we provide a detailed insight into recent trends in molecular aggregates from the perspectives of nanoarchitectonics.

Structural organization of surfactant aggregates in vacuo: a molecular dynamics and well-tempered metadynamics study.

PubMed

Longhi, Giovanna; Fornili, Sandro L; Turco Liveri, Vincenzo

2015-07-07

Experimental investigations using mass spectrometry have established that surfactant molecules are able to form aggregates in the gas phase. However, there is no general consensus on the organization of these aggregates and how it depends on the aggregation number and surfactant molecular structure. In the present paper we investigate the structural organization of some surfactants in vacuo by molecular dynamics and well-tempered metadynamics simulations to widely explore the space of their possible conformations in vacuo. To study how the specific molecular features of such compounds affect their organization, we have considered as paradigmatic surfactants, the anionic single-chain sodium dodecyl sulfate (SDS), the anionic double-chain sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and the zwitterionic single-chain dodecyl phosphatidyl choline (DPC) within a wide aggregation number range (from 5 to 100). We observe that for low aggregation numbers the aggregates show in vacuo the typical structure of reverse micelles, while for large aggregation numbers a variety of globular aggregates occur that are characterized by the coexistence of interlaced domains formed by the polar or ionic heads and by the alkyl chains of the surfactants. Well-tempered metadynamics simulations allows us to confirm that the structural organizations obtained after 50 ns of molecular dynamics simulations are practically the equilibrium ones. Similarities and differences of surfactant aggregates in vacuo and in apolar media are also discussed.

Regulation of substituent groups on morphologies and self-assembly of organogels based on some azobenzene imide derivatives

NASA Astrophysics Data System (ADS)

Jiao, Tifeng; Wang, Yujin; Zhang, Qingrui; Zhou, Jingxin; Gao, Faming

2013-04-01

In this paper, new azobenzene imide derivatives with different substituent groups were designed and synthesized. Their gelation behaviors in 21 solvents were tested as novel low-molecular-mass organic gelators. It was shown that the alkyl substituent chains and headgroups of azobenzene residues in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. More alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle, lamella, and belt to fiber with the change of solvents. Spectral studies indicated that there existed different H-bond formations between amide groups and conformations of methyl chains. The present work may give some insight to the design and character of new organogelators and soft materials with special molecular structures.

Regulation of substituent groups on morphologies and self-assembly of organogels based on some azobenzene imide derivatives

PubMed Central

2013-01-01

In this paper, new azobenzene imide derivatives with different substituent groups were designed and synthesized. Their gelation behaviors in 21 solvents were tested as novel low-molecular-mass organic gelators. It was shown that the alkyl substituent chains and headgroups of azobenzene residues in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. More alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle, lamella, and belt to fiber with the change of solvents. Spectral studies indicated that there existed different H-bond formations between amide groups and conformations of methyl chains. The present work may give some insight to the design and character of new organogelators and soft materials with special molecular structures. PMID:23566628

Relaxation times and modes of disturbed aggregate distribution in micellar solutions with fusion and fission of micelles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zakharov, Anatoly I.; Adzhemyan, Loran Ts.; Shchekin, Alexander K., E-mail: akshch@list.ru

2015-09-28

We have performed direct numerical calculations of the kinetics of relaxation in the system of surfactant spherical micelles under joint action of the molecular mechanism with capture and emission of individual surfactant molecules by molecular aggregates and the mechanism of fusion and fission of the aggregates. As a basis, we have taken the difference equations of aggregation and fragmentation in the form of the generalized kinetic Smoluchowski equations for aggregate concentrations. The calculations have been made with using the droplet model of molecular surfactant aggregates and two modified Smoluchowski models for the coefficients of aggregate-monomer and aggregate-aggregate fusions which takemore » into account the effects of the aggregate size and presence of hydrophobic spots on the aggregate surface. A full set of relaxation times and corresponding relaxation modes for nonequilibrium aggregate distribution in the aggregation number has been found. The dependencies of these relaxation times and modes on the total concentration of surfactant in the solution and the special parameter controlling the probability of fusion in collisions of micelles with other micelles have been studied.« less

Analysis of self-oscillating behaviors aimed at the development of a molecular robot with organic acids as fuel

NASA Astrophysics Data System (ADS)

Nakazumi, Tomoka; Hara, Yusuke

2017-09-01

We studied the transmittance self-oscillation of a polymer chain driven by an organic acid as the fuel. The self-oscillating polymer chain consists of 4-acryloylmorpholine (ACMO) and the Ru catalyst (Ru(bpy)3) of the Belousov-Zhabotinsky (BZ) reaction. The transmittance self-oscillating behavior was affected significantly by the temperature. As the amplitude of the transmittance self-oscillation, which is reflected by the aggregation state, decreased with time, the oscillation period also decreased. This trend indicates that the polymer aggregation affects the rate of the BZ reaction significantly. The activation energy of the self-oscillating value was almost the same in the normal BZ reaction, which does not include Ru(bpy)3 complexes in the polymer chains. In addition, we demonstrated the effect of one BZ substrate (sodium bromate or malonic acid) on the transmittance self-oscillation period.

Entropic effects, shape, and size of mixed micelles formed by copolymers with complex architectures

NASA Astrophysics Data System (ADS)

Kalogirou, Andreas; Gergidis, Leonidas N.; Moultos, Othonas; Vlahos, Costas

2015-11-01

The entropic effects in the comicellization behavior of amphiphilic A B copolymers differing in the chain size of solvophilic A parts were studied by means of molecular dynamics simulations. In particular, mixtures of miktoarm star copolymers differing in the molecular weight of solvophilic arms were investigated. We found that the critical micelle concentration values show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This can be attributed to the effective interactions between copolymers originated from the arm size asymmetry. The effective interactions induce a very small decrease in the aggregation number of preferential micelles triggering the nonrandom mixing between the solvophilic moieties in the corona. Additionally, in order to specify how the chain architecture affects the size distribution and the shape of mixed micelles we studied star-shaped, H-shaped, and homo-linked-rings-linear mixtures. In the first case the individual constituents form micelles with preferential and wide aggregation numbers and in the latter case the individual constituents form wormlike and spherical micelles.

Entropic effects, shape, and size of mixed micelles formed by copolymers with complex architectures.

PubMed

Kalogirou, Andreas; Gergidis, Leonidas N; Moultos, Othonas; Vlahos, Costas

2015-11-01

The entropic effects in the comicellization behavior of amphiphilic AB copolymers differing in the chain size of solvophilic A parts were studied by means of molecular dynamics simulations. In particular, mixtures of miktoarm star copolymers differing in the molecular weight of solvophilic arms were investigated. We found that the critical micelle concentration values show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This can be attributed to the effective interactions between copolymers originated from the arm size asymmetry. The effective interactions induce a very small decrease in the aggregation number of preferential micelles triggering the nonrandom mixing between the solvophilic moieties in the corona. Additionally, in order to specify how the chain architecture affects the size distribution and the shape of mixed micelles we studied star-shaped, H-shaped, and homo-linked-rings-linear mixtures. In the first case the individual constituents form micelles with preferential and wide aggregation numbers and in the latter case the individual constituents form wormlike and spherical micelles.

Aggregation Pathways of Native-Like Ubiquitin Promoted by Single-Point Mutation, Metal Ion Concentration, and Dielectric Constant of the Medium.

PubMed

Fermani, Simona; Calvaresi, Matteo; Mangini, Vincenzo; Falini, Giuseppe; Bottoni, Andrea; Natile, Giovanni; Arnesano, Fabio

2018-03-15

Ubiquitin-positive protein aggregates are biomarkers of neurodegeneration, but the molecular mechanism responsible for their formation and accumulation is still unclear. Possible aggregation pathways of human ubiquitin (hUb) promoted by both intrinsic and extrinsic factors, are here investigated. By a computational analysis, two different hUb dimers are indicated as possible precursors of amyloid-like structures, but their formation is disfavored by an electrostatic repulsion involving Glu16 and other carboxylate residues present at the dimer interface. Experimental data on the E16V mutant of hUb shows that this single-point mutation, although not affecting the overall protein conformation, promotes protein aggregation. It is sufficient to shift the same mutation by only two residues (E18V) to regain the behavior of wild-type hUb. The neutralization of Glu16 negative charge by a metal ion and a decrease of the dielectric constant of the medium by addition of trifluoroethanol (TFE), also promote hUb aggregation. The outcomes of this research have important implications for the prediction of physiological parameters that favor aggregate formation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Redox-Triggered Bonding-Induced Emission of Thiol-Functionalized Gold Nanoclusters for Luminescence Turn-On Detection of Molecular Oxygen.

PubMed

Ao, Hang; Feng, Hui; Zhao, Mengting; Zhao, Meizhi; Chen, Jianrong; Qian, Zhaosheng

2017-11-22

Most optical sensors for molecular oxygen were developed based on the quenching effect of the luminescence of oxygen-sensitive probes; however, the signal turn-off mode of these probes is undesirable to quantify and visualize molecular oxygen. Herein, we report a novel luminescence turn-on detection strategy for molecular oxygen via the specific oxygen-triggered bonding-induced emission of thiol-functionalized gold nanoclusters. Thiol-functionalized gold nanoclusters were prepared by a facile one-step synthesis, and as-prepared gold nanoclusters possess significant aggregation-induced emission (AIE) property. It is the first time to discover the oxygen-triggered bonding-induced emission (BIE) behavior of gold nanoclusters, which results in disulfide-linked covalent bonding assemblies with intensely red luminescence. This specific redox-triggered BIE is capable of quantitatively detecting dissolved oxygen in aqueous solution in a light-up manner, and trace amount of dissolved oxygen at ppb level is achieved based on this detection method. A facile and convenient test strip for oxygen detection was also developed to monitor molecular oxygen in a gas matrix. Covalent bonding-induced emission is proven to be a more efficient way to attain high brightness of AIEgens than a physical aggregation-induced emission process, and provides a more convenient and desirable detection method for molecular oxygen than the previous sensors.

Tunneling electron induced molecular electroluminescence from individual porphyrin J-aggregates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, Qiushi; Zhang, Chao; Zhang, Yang, E-mail: zhyangnano@ustc.edu.cn, E-mail: zcdong@ustc.edu.cn

2015-07-27

We investigate molecular electroluminescence from individual tubular porphyrin J-aggregates on Au(111) by tunneling electron excitations in an ultrahigh-vacuum scanning tunneling microscope (STM). High-resolution STM images suggest a spiral tubular structure for the porphyrin J-aggregate with highly ordered “brickwork”-like arrangements. Such aggregated nanotube is found to behave like a self-decoupled molecular architecture and shows red-shifted electroluminescence characteristics of J-aggregates originated from the delocalized excitons. The positions of the emission peaks are found to shift slightly depending on the excitation sites, which, together with the changes in the observed spectral profiles with vibronic progressions, suggest a limited exciton coherence number within severalmore » molecules. The J-aggregate electroluminescence is also found unipolar, occurring only at negative sample voltages, which is presumably related to the junction asymmetry in the context of molecular excitations via the carrier injection mechanism.« less

Anomalous Micellization of Pluronic Block Copolymers

NASA Astrophysics Data System (ADS)

Leonardi, Amanda; Ryu, Chang Y.

2014-03-01

Poly(ethylene oxide) - poly(propylene oxide) - poly(ethylene oxide) (PEO-PPO-PEO) block copolymers, commercially known as Pluronics, are a unique family of amphiphilic triblock polymers, which self-assemble into micelles in aqueous solution. These copolymers have shown promise in therapeutic, biomedical, cosmetic, and nanotech applications. As-received samples of Pluronics contain low molecular weight impurities (introduced during the manufacturing and processing), that are ignored in most applications. It has been observed, however, that in semi-dilute aqueous solutions, at concentrations above 1 wt%, the temperature dependent micellization behavior of the Pluronics is altered. Anomalous behavior includes a shift of the critical micellization temperature and formation of large aggregates at intermediate temperatures before stable sized micelles form. We attribute this behavior to the low molecular weight impurities that are inherent to the Pluronics which interfere with the micellization process. Through the use of Dynamic Light Scattering and HPLC, we compared the anomalous behavior of different Pluronics of different impurity levels to their purified counterparts.

Diarmed (adamantyl/alkyl) surfactants from nitrilotriacetic acid.

PubMed

Trillo, Juan V; Vázquez Tato, José; Jover, Aida; de Frutos, Santiago; Soto, Victor H; Galantini, Luciano; Meijide, Francisco

2014-11-01

The compounds presented here constitute a clear example of molecular biomimetics as their design is inspired on the structure and properties of natural phospholipids. Thus novel double-armed surfactants have been obtained in which nitrilotriacetic acid plays the role of glycerol in phospholipids. The hydrophobic arms are linked to the head group through amide bonds (which is also the case of sphingomyelin): (R1NHCOCH2)(R2NHCOCH2)NCH2CO2H (R1 being CH3(CH2)11, CH3(CH2)17, CH3(CH2)7CHCH(CH2)8, and adamantyl, and R2=adamantyl). The dependence of the surface tension with concentration shows the typical profile of surfactants since a breaking point, which corresponds to the critical aggregation concentration (cac), is observed in all cases. The cac of these diarmed derivatives are about 1-3 orders of magnitude lower than those of classical monoalkyl derivatives used as reference compounds. In contrast to conventional surfactants, reversed trends in cac values and molecular areas at the solution-air interface have been observed. This anomalous behavior is tied to the structure of the surfactants and suggests that long and flexible alkyl chains should self-coil previous to the aggregation or adsorption phenomena. Above cac all compounds form large aggregates, globular in shape, which tend to associate forming giant aggregates. Copyright © 2014 Elsevier B.V. All rights reserved.

Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Tulla, Kiara A; Maker, Ajay V

2018-03-01

Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia. A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines. Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia. Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.

Self-organization of intertidal snails facilitates evolution of aggregation behavior.

PubMed

Stafford, Richard; Davies, Mark S; Williams, Gray A

2008-01-01

Many intertidal snails form aggregations during emersion to minimize desiccation stress. Here we investigate possible mechanisms for the evolution of such behavior. Two behavioral traits (following of mucus trails, and crevice occupation), which both provide selective advantages to individuals that possess the traits over individuals that do not, result in self-organization of aggregations in crevices in the rock surface. We suggest that the existence of self-organizing aggregations provides a mechanism by which aggregation behavior can evolve. The inclusion of an explicitly coded third behavior, aggregation, in a simulated population produces patterns statistically similar to those found on real rocky shores. Allowing these three behaviors to evolve using an evolutionary algorithm, however, results in aggregation behavior being selected against on shores with high crevice density. The inclusion of broadcast spawning dispersal mechanisms in the simulation, however, results in aggregation behavior evolving as predicted on shores with both high crevice density and low crevice density (evolving in crevices first, and then both in crevices and on flat rock), indicating the importance of environmental interactions in understanding evolutionary processes. We propose that self-organization can be an important factor in the evolution of group behaviors.

Unusual properties of aqueous solutions of L-proline: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Civera, Monica; Sironi, Maurizio; Fornili, Sandro L.

2005-11-01

Aqueous solutions of the bioprotectant proline are simulated for solute molar fractions ranging from 2.0 × 10 -3 to 2.3 × 10 -1. Statistical analyses show that proline affects the water structure more strongly than glycine betaine and trimethylamine- N-oxide, two of the most effective bioprotectants widely diffuse in nature, and as strongly as tert-butyl alcohol, a protein denaturant which at high concentration self-aggregates. No evidence is found, however, that proline self-aggregates as it has been previously suggested to explain experimental findings on concentrated proline solutions. Nevertheless, the behavior of the diffusion coefficients of proline and water vs. solute concentration qualitatively agrees with such results.

Dietary flavonoids: molecular mechanisms of action as anti- inflammatory agents.

PubMed

Marzocchella, Laura; Fantini, Massimo; Benvenuto, Monica; Masuelli, Laura; Tresoldi, Ilaria; Modesti, Andrea; Bei, Roberto

2011-09-01

Flavonoids are a large group of polyphenolic compounds, which are ubiquitously expressed in plants. They are grouped according to their chemical structure and function into flavonols, flavones, flavan-3-ols, anthocyanins, flavanones and isoflavones. Many of flavonoids are found in fruits, vegetables and beverages. Flavonoids have been demonstrated to have advantageous effects on human health because their anti-allergic, anti-inflammatory, anti-platelet aggregation, anti-tumor and anti-oxidant behavior. This report reviews the current knowledge on the molecular mechanisms of action of flavonoids as anti-inflammatory agents and also discusses the relevant patents.

Surface properties and aggregate morphology of partially fluorinated carboxylate-type anionic gemini surfactants.

PubMed

Yoshimura, Tomokazu; Bong, Miri; Matsuoka, Keisuke; Honda, Chikako; Endo, Kazutoyo

2009-11-01

Three anionic homologues of a novel partially fluorinated carboxylate-type anionic gemini surfactant, N,N'-di(3-perfluoroalkyl-2-hydroxypropyl)-N,N'-diacetic acid ethylenediamine (2C(n)(F) edda, where n represents the number of carbon atoms in the fluorocarbon chain (4, 6, and 8)) were synthesized. In these present gemini surfactants, the relatively small carboxylic acid moieties form hydrophilic head groups. The surface properties or structures of the aggregates of these surfactants are strongly influenced by the nonflexible fluorocarbons and small head groups; this is because these surfactants have a closely packed molecular structure. The equilibrium surface tension properties of these surfactants were measured at 298.2K for various fluorocarbon chain lengths. The plot of the logarithm of the critical micelle concentration (cmc) against the fluorocarbon chain lengths for 2C(n)(F) edda (n=4, 6, and 8) showed a minimum for n=6. Furthermore, the lowest surface tension of 2C(6)(F) edda at the cmc was 16.4mNm(-1). Such unique behavior has not been observed even in the other fluorinated surfactants. Changes in the shapes and sizes of these surfactant aggregate with concentration were investigated by dynamic light scattering and transmission electron microscopy (TEM). The TEM micrographs showed that in an aqueous alkali solution, 2C(n)(F) edda mainly formed aggregates with stringlike (n=4), cagelike (n=6), and distorted bilayer structures (n=8). The morphological changes in the aggregates were affected by the molecular structure composed of nonflexible fluorocarbon chains and flexible hydrocarbon chains.

Why Huddle? Ecological Drivers of Chick Aggregations in Gentoo Penguins, Pygoscelis papua, across Latitudes

PubMed Central

Collen, Ben; Johnston, Daniel

2016-01-01

Aggregations of young animals are common in a range of endothermic and ectothermic species, yet the adaptive behavior may depend on social circumstance and local conditions. In penguins, many species form aggregations (aka. crèches) for a variety of purposes, whilst others have never been observed exhibiting this behavior. Those that do form aggregations do so for three known benefits: 1) reduced thermoregulatory requirements, 2) avoidance of unrelated-adult aggression, and 3) lower predation risk. In gentoo penguins, Pygoscelis papua, chick aggregations are known to form during the post-guard period, yet the cause of these aggregations is poorly understood. Here, for the first time, we study aggregation behavior in gentoo penguins, examining four study sites along a latitudinal gradient using time-lapse cameras to examine the adaptive benefit of aggregations to chicks. Our results support the idea that aggregations of gentoo chicks decrease an individual’s energetic expenditure when wet, cold conditions are present. However, we found significant differences in aggregation behavior between the lowest latitude site, Maiviken, South Georgia, and two of the higher latitude sites on the Antarctic Peninsula, suggesting this behavior may be colony specific. We provide strong evidence that more chicks aggregate and a larger number of aggregations occur on South Georgia, while the opposite occurs at Petermann Island in Antarctica. Future studies should evaluate multiple seabird colonies within one species before generalizing behaviors based on one location, and past studies may need to be re-evaluated to determine whether chick aggregation and other behaviors are in fact exhibited species-wide. PMID:26840252

Why Huddle? Ecological Drivers of Chick Aggregations in Gentoo Penguins, Pygoscelis papua, across Latitudes.

PubMed

Black, Caitlin; Collen, Ben; Johnston, Daniel; Hart, Tom

2016-01-01

Aggregations of young animals are common in a range of endothermic and ectothermic species, yet the adaptive behavior may depend on social circumstance and local conditions. In penguins, many species form aggregations (aka. crèches) for a variety of purposes, whilst others have never been observed exhibiting this behavior. Those that do form aggregations do so for three known benefits: 1) reduced thermoregulatory requirements, 2) avoidance of unrelated-adult aggression, and 3) lower predation risk. In gentoo penguins, Pygoscelis papua, chick aggregations are known to form during the post-guard period, yet the cause of these aggregations is poorly understood. Here, for the first time, we study aggregation behavior in gentoo penguins, examining four study sites along a latitudinal gradient using time-lapse cameras to examine the adaptive benefit of aggregations to chicks. Our results support the idea that aggregations of gentoo chicks decrease an individual's energetic expenditure when wet, cold conditions are present. However, we found significant differences in aggregation behavior between the lowest latitude site, Maiviken, South Georgia, and two of the higher latitude sites on the Antarctic Peninsula, suggesting this behavior may be colony specific. We provide strong evidence that more chicks aggregate and a larger number of aggregations occur on South Georgia, while the opposite occurs at Petermann Island in Antarctica. Future studies should evaluate multiple seabird colonies within one species before generalizing behaviors based on one location, and past studies may need to be re-evaluated to determine whether chick aggregation and other behaviors are in fact exhibited species-wide.

A Supramolecular Ice Growth Inhibitor.

PubMed

Drori, Ran; Li, Chao; Hu, Chunhua; Raiteri, Paolo; Rohl, Andrew L; Ward, Michael D; Kahr, Bart

2016-10-12

Safranine O, a synthetic dye, was found to inhibit growth of ice at millimolar concentrations with an activity comparable to that of highly evolved antifreeze glycoproteins. Safranine inhibits growth of ice crystals along the crystallographic a-axis, resulting in bipyramidal needles extended along the <0001> directions as well as and plane-specific thermal hysteresis (TH) activity. The interaction of safranine with ice is reversible, distinct from the previously reported behavior of antifreeze proteins. Spectroscopy and molecular dynamics indicate that safranine forms aggregates in aqueous solution at micromolar concentrations. Metadynamics simulations and aggregation theory suggested that as many as 30 safranine molecules were preorganized in stacks at the concentrations where ice growth inhibition was observed. The simulations and single-crystal X-ray structure of safranine revealed regularly spaced amino and methyl substituents in the aggregates, akin to the ice-binding site of antifreeze proteins. Collectively, these observations suggest an unusual link between supramolecular assemblies of small molecules and functional proteins.

Naphthalene based AIE active stimuli-responsive material as rewritable media for temporary communication

NASA Astrophysics Data System (ADS)

Pannipara, Mehboobali; Al-Sehemi, Abdullah G.; Kalam, Abul; Asiri, Abdullah M.

2017-10-01

Organic molecules having extended π-conjugated moieties is useful for creating 'dynamic' functional materials by modulating the photophysical properties and molecular packing through non-covalent interactions. Herein, we report the photoluminescence properties of a luminogen, NBA, exhibiting aggregation-induced emission (AIE) characteristics, synthesized by Knoevenagel condensation reaction between 2-Hydroxy naphthaldehyde and malononitrile. NBA emits strongly upon aggregation and in solid state with large Stokes shift whereas it is non emissive in pure solvents. The aggregation induced emission behavior of the compound was carried out in DMSO (good solvent)-water mixture (poor solvent) with water fraction (fw) ranging from 0% to 98%. The AIE property of the luminogen were further exploited for fabricating rewritable fluorescent paper substrates that found applications in security printing and data storage where the written images or letters stored on the filter paper are invisible under normal light.

The Physics of Protoplanetesimal Dust Agglomerates. VII. The Low-velocity Collision Behavior of Large Dust Agglomerates

NASA Astrophysics Data System (ADS)

Schräpler, Rainer; Blum, Jürgen; Seizinger, Alexander; Kley, Wilhelm

2012-10-01

We performed micro-gravity collision experiments in our laboratory drop tower using 5 cm sized dust agglomerates with volume filling factors of 0.3 and 0.4, respectively. This work is an extension of our previous experiments reported in Beitz et al. to aggregates of more than one order of magnitude higher masses. The dust aggregates consisted of micrometer-sized silica particles and were macroscopically homogeneous. We measured the coefficient of restitution for collision velocities ranging from 1 cm s-1 to 0.5 m s-1, and determined the fragmentation velocity. For low velocities, the coefficient of restitution decreases with increasing impact velocity, in contrast to findings by Beitz et al. At higher velocities, the value of the coefficient of restitution becomes constant, before the aggregates break at the onset of fragmentation. We interpret the qualitative change in the coefficient of restitution as the transition from a solid-body-dominated to a granular-medium-dominated behavior. We complement our experiments by molecular-dynamics simulations of porous aggregates and obtain a reasonable match to the experimental data. We discuss the importance of our experiments for protoplanetary disks, debris disks, and planetary rings. This work is an extension to the previous work of our group and gives new insight into the velocity dependency of the coefficient of restitution due to improved measurements, better statistics, and a theoretical approach.

Molecular Dynamics Study of the Solubility Curve of Polyglutamine for the PLUM Model.

NASA Astrophysics Data System (ADS)

Kutlu, Songul; Haaga, Jason; Gunton, James D.

A recent study by Crick et al determined the saturation (solubility) curve for polyglutamine (PolyQ) for several different repeat lengths, n, of Qn, and for different flanking sequences, such as K2. The degree of supersaturation S, (S =ln(Co/Ce), where Co and Ce are the metastable and equilibrium saturation monomer concentrations, respectively) plays a crucial role in the kinetics of aggregation of misfolded proteins containing polyQ. Thus the degree of supersaturation is an important factor in diseases such as Huntington's disease for which polyQ is a major component. We present here preliminary results of a molecular dynamics study for the solubility curve for a PLUM model of Q10. (An extensive study of the kinetics of aggregation for this model is being carried out in a separate study) Our results display a normal solubility curve behavior, with the saturation concentration increasing with increasing temperature. This is only in partial qualitative agreement with the experimental results, which show a retrograde behavior at low temperatures. We are extending this study to other repeat lengths, including Q40. ∖ ∖ ∖ ∖ This work is supported by the G. Harold and Leila Y. Mathers Foundation and used an allocation of time from XSEDE.

Coarse-grained molecular simulation of self-assembly for nonionic surfactants on graphene nanostructures.

PubMed

Wu, Dan; Yang, Xiaoning

2012-10-04

Self-assembly of amphiphilic molecules on the surfaces of nanoscale materials has an important application in a variety of nanotechnology. Here, we report a coarse-grained molecular dynamics simulation on the structure and morphology of the nonionic surfactant, n-alkyl poly(ethylene oxide) (PEO), adsorbed on planar graphene nanostructures. The effects of concentration, surfactant structure, and size of graphene sheet are explored. Because of the finite dimension effect, various morphological hemimicelles can be formed on nanoscale graphene surfaces, which is somewhat different from the self-assembly structures on infinite carbon surfaces. The aggregate morphology is highly dependent on the concentration, the chain lengths, and the size of graphene nanosheets. For the nonionic surfactant, the PEO headgroups show strong dispersion interaction with the carbon surface, leading to a side edge adsorption behavior. This simulation provides insight into the supramolecular self-assembly nanostructures and the adsorption mechanism for the nonionic surfactants aggregated on graphene nanostructures, which could be exploited to guide fabrication of graphene-based nanocomposites.

Impact of Supramolecular Aggregation on the Crystallization Kinetics of Organic Compounds from the Supercooled Liquid State.

PubMed

Kalra, Arjun; Tishmack, Patrick; Lubach, Joseph W; Munson, Eric J; Taylor, Lynne S; Byrn, Stephen R; Li, Tonglei

2017-06-05

Despite numerous challenges in their theoretical description and practical implementation, amorphous drugs are of growing importance to the pharmaceutical industry. One such challenge is to gain molecular level understanding of the propensity of a molecule to form and remain as a glassy solid. In this study, a series of structurally similar diarylamine compounds was examined to elucidate the role of supramolecular aggregation on crystallization kinetics from supercooled liquid state. The structural similarity of the compounds makes it easier to isolate the molecular features that affect crystallization kinetics and glass forming ability of these compounds. To examine the role of hydrogen-bonded aggregation and motifs on crystallization kinetics, a combination of thermal and spectroscopic techniques was employed. Using variable temperature FTIR, Raman, and solid-state NMR spectroscopies, the presence of hydrogen bonding in the melt and glassy state was examined and correlated with observed phase transition behaviors. Spectroscopic results revealed that the formation of hydrogen-bonded aggregates involving carboxylic acid and pyridine nitrogen (acid-pyridine aggregates) between neighboring molecules in the melt state impedes crystallization, while the presence of carboxylic acid dimers (acid-acid dimers) in the melt favors crystallization. This study suggests that glass formation of small molecules is influenced by the type of intermolecular interactions present in the melt state and the kinetics associated with the molecules to assemble into a crystalline lattice. For the compounds that form acid-pyridine aggregates, the formation of energy degenerate chains, produced due to conformational flexibility of the molecules, presents a kinetic barrier to crystallization. The poor crystallization tendency of these aggregates stems from the highly directional hydrogen-bonding interactions needed to form the acid-pyridine chains. Conversely, for the compounds that form acid-acid dimers, the nondirectional van der Waals forces needed to construct a nucleus promote rapid assembly and crystallization.

Strategies toward High Performance Organic Photovoltaic Cell: Material and Process

NASA Astrophysics Data System (ADS)

Kim, Bong Gi

The power conversion efficiency of organic photovoltaic (OPV) cells has been rapidly improved during the last few years and currently reaches around 10 %. The performance is evenly governed by absorption, exciton diffusion, exciton dissociation, carrier transfer, and collection efficiencies. Establishing a better understanding of OPV device physics combined with the development of new materials for each executive step contributes to this dramatic improvement. This dissertation focuses mainly on material design and development to correlate the intrinsic properties of organic semiconductors and the OPV performance. The introductory Chapter 1 briefly reviews the motivation of OPV research, its working mechanism, and representative organic materials for OPV application. Chapter 2 discusses the modulation of conjugated polymer's (CP's) absorption behavior and an efficient semi-empirical approach to predict CP's energy levels from its constituent monomers' HOMO/LUMO values. A strong acceptor lowered both the HOMO and LUMO levels of the CP, but the LUMO dropped more rapidly which ultimately produced a narrowed band-gap in the electron donating/accepting alternating copolymer system. In addition, the energy level difference between the CP and the constituent monomers converged to a constant value, providing an energy level prediction tool. Chapter 3 illustrates the systematic investigation on the relationship between the molecular structure of an energy harvesting organic dye and the exciton dissociation efficiency. The study showed that the quantum yield decreased as the exciton binding energy increases, and dipole moment direction should be properly oriented in the dye framework in order to improve photo-current generation when used in a dye sensitized photovoltaic device. Chapter 4 demonstrates the ultrasonic-assisted self-assembly of CPs in solution, rapidly and efficiently. Ultrasonication combined with dipolar media accelerated CP's aggregation, and the effect of CP's aggregation on the enhancement of OPV performance by promoting photo-current generation and increasing carrier mobility was systematically investigated. The correlation between the chemical structure of a CP and it aggregation behavior is further described in Chapter 5. To promote CP aggregate, a planar chain conformation was advantageous and CP aggregation improved hole mobility in the OPV device. However, thermally induced CP aggregates caused strong charge recombination, resulting in open circuit voltage drop. In Chapter 6, a novel polymer design principle to enable directed CP alignment is discussed. Regulating chain planarity and preventing massive crystallization of CP achieved by the developed molecular design principle allowed directed CP alignment under small shear flow.

Behavior-based aggregation of land categories for temporal change analysis

NASA Astrophysics Data System (ADS)

Aldwaik, Safaa Zakaria; Onsted, Jeffrey A.; Pontius, Robert Gilmore, Jr.

2015-03-01

Comparison between two time points of the same categorical variable for the same study extent can reveal changes among categories over time, such as transitions among land categories. If many categories exist, then analysis can be difficult to interpret. Category aggregation is the procedure that combines two or more categories to create a single broader category. Aggregation can simplify interpretation, and can also influence the sizes and types of changes. Some classifications have an a priori hierarchy to facilitate aggregation, but an a priori aggregation might make researchers blind to important category dynamics. We created an algorithm to aggregate categories in a sequence of steps based on the categories' behaviors in terms of gross losses and gross gains. The behavior-based algorithm aggregates net gaining categories with net gaining categories and aggregates net losing categories with net losing categories, but never aggregates a net gaining category with a net losing category. The behavior-based algorithm at each step in the sequence maintains net change and maximizes swap change. We present a case study where data from 2001 and 2006 for 64 land categories indicate change on 17% of the study extent. The behavior-based algorithm produces a set of 10 categories that maintains nearly the original amount of change. In contrast, an a priori aggregation produces 10 categories while reducing the change to 9%. We offer a free computer program to perform the behavior-based aggregation.

Self-assembly of organogels via new luminol imide derivatives: diverse nanostructures and substituent chain effect

PubMed Central

2013-01-01

Luminol is considered as an efficient sycpstem in electrochemiluminescence (ECL) measurements for the detection of hydrogen peroxide. In this paper, new luminol imide derivatives with different alkyl substituent chains were designed and synthesized. Their gelation behaviors in 26 solvents were tested as novel low molecular mass organic gelators. It was shown that the length and number of alkyl substituent chains linked to a benzene ring in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. Longer alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscope and atomic force microscope observations revealed that the gelator molecules self-assemble into different micro/nanoscale aggregates from a dot, flower, belt, rod, and lamella to wrinkle with change of solvents. Spectral studies indicated that there existed different H-bond formations and hydrophobic forces, depending on the alkyl substituent chains in molecular skeletons. The present work may give some insight to the design and characteristic of new versatile soft materials and potential ECL biosensors with special molecular structures. PMID:23758979

Self-assembly of organogels via new luminol imide derivatives: diverse nanostructures and substituent chain effect

NASA Astrophysics Data System (ADS)

Jiao, Tifeng; Huang, Qinqin; Zhang, Qingrui; Xiao, Debao; Zhou, Jingxin; Gao, Faming

2013-06-01

Luminol is considered as an efficient sycpstem in electrochemiluminescence (ECL) measurements for the detection of hydrogen peroxide. In this paper, new luminol imide derivatives with different alkyl substituent chains were designed and synthesized. Their gelation behaviors in 26 solvents were tested as novel low molecular mass organic gelators. It was shown that the length and number of alkyl substituent chains linked to a benzene ring in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. Longer alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscope and atomic force microscope observations revealed that the gelator molecules self-assemble into different micro/nanoscale aggregates from a dot, flower, belt, rod, and lamella to wrinkle with change of solvents. Spectral studies indicated that there existed different H-bond formations and hydrophobic forces, depending on the alkyl substituent chains in molecular skeletons. The present work may give some insight to the design and characteristic of new versatile soft materials and potential ECL biosensors with special molecular structures.

Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways

PubMed Central

Douglas, Peter M; Summers, Daniel W

2009-01-01

The self-association of misfolded or damaged proteins into ordered amyloid-like aggregates characterizes numerous neurodegenerative disorders. Insoluble amyloid plaques are diagnostic of many disease states. Yet soluble, oligomeric intermediates in the aggregation pathway appear to represent the toxic culprit. Molecular chaperones regulate the fate of misfolded proteins and thereby influence their aggregation state. Chaperones conventionally antagonize aggregation of misfolded, disease proteins and assist in refolding or degradation pathways. Recent work suggests that chaperones may also suppress neurotoxicity by converting toxic, soluble oligomers into benign aggregates. Chaperones can therefore suppress or promote aggregation of disease proteins to ameliorate the proteotoxic accumulation of soluble, assembly intermediates. PMID:19421006

Identifying Mechanisms of Interfacial Dynamics Using Single-Molecule Tracking

PubMed Central

Kastantin, Mark; Walder, Robert; Schwartz, Daniel K.

2012-01-01

The “soft” (i.e. non-covalent) interactions between molecules and surfaces are complex and highly-varied (e.g. hydrophobic, hydrogen bonding, ionic) often leading to heterogeneous interfacial behavior. Heterogeneity can arise either from spatial variation of the surface/interface itself or from molecular configurations (i.e. conformation, orientation, aggregation state, etc.). By observing adsorption, diffusion, and desorption of individual fluorescent molecules, single-molecule tracking can characterize these types of heterogeneous interfacial behavior in ways that are inaccessible to traditional ensemble-averaged methods. Moreover, the fluorescence intensity or emission wavelength (in resonance energy transfer experiments) can be used to simultaneously track molecular configuration and directly relate this to the resulting interfacial mobility or affinity. In this feature article, we review recent advances involving the use of single-molecule tracking to characterize heterogeneous molecule-surface interactions including: multiple modes of diffusion and desorption associated with both internal and external molecular configuration, Arrhenius activated interfacial transport, spatially dependent interactions, and many more. PMID:22716995

Molecular-level insights of early-stage prion protein aggregation on mica and gold surface determined by AFM imaging and molecular simulation.

PubMed

Lou, Zhichao; Wang, Bin; Guo, Cunlan; Wang, Kun; Zhang, Haiqian; Xu, Bingqian

2015-11-01

By in situ time-lapse AFM, we investigated early-stage aggregates of PrP formed at low concentration (100 ng/mL) on mica and Au(111) surfaces in acetate buffer (pH 4.5). Remarkably different PrP assemblies were observed. Oligomeric structures of PrP aggregates were observed on mica surface, which was in sharp contrast to the multi-layer PrP aggregates yielding parallel linear patterns observed Au(111) surface. Combining molecular dynamics and docking simulations, PrP monomers, dimers and trimers were revealed as the basic units of the observed aggregates. Besides, the mechanisms of the observed PrP aggregations and the corresponding molecular-substrate and intermolecular interactions were suggested. These interactions involved gold-sulfur interaction, electrostatic interaction, hydrophobic interaction, and hydrogen binding interaction. In contrast, the PrP aggregates observed in pH 7.2 PBS buffer demonstrated similar large ball-like structures on both mica and Au(111) surfaces. The results indicate that the pH of a solution and the surface of the system can have strong effects on supramolecular assemblies of prion proteins. This study provides in-depth understanding on the structural and mechanistic nature of PrP aggregation, and can be used to study the aggregation mechanisms of other proteins with similar misfolding properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Data-driven modeling reveals cell behaviors controlling self-organization during Myxococcus xanthus development

PubMed Central

Cotter, Christopher R.; Schüttler, Heinz-Bernd; Igoshin, Oleg A.; Shimkets, Lawrence J.

2017-01-01

Collective cell movement is critical to the emergent properties of many multicellular systems, including microbial self-organization in biofilms, embryogenesis, wound healing, and cancer metastasis. However, even the best-studied systems lack a complete picture of how diverse physical and chemical cues act upon individual cells to ensure coordinated multicellular behavior. Known for its social developmental cycle, the bacterium Myxococcus xanthus uses coordinated movement to generate three-dimensional aggregates called fruiting bodies. Despite extensive progress in identifying genes controlling fruiting body development, cell behaviors and cell–cell communication mechanisms that mediate aggregation are largely unknown. We developed an approach to examine emergent behaviors that couples fluorescent cell tracking with data-driven models. A unique feature of this approach is the ability to identify cell behaviors affecting the observed aggregation dynamics without full knowledge of the underlying biological mechanisms. The fluorescent cell tracking revealed large deviations in the behavior of individual cells. Our modeling method indicated that decreased cell motility inside the aggregates, a biased walk toward aggregate centroids, and alignment among neighboring cells in a radial direction to the nearest aggregate are behaviors that enhance aggregation dynamics. Our modeling method also revealed that aggregation is generally robust to perturbations in these behaviors and identified possible compensatory mechanisms. The resulting approach of directly combining behavior quantification with data-driven simulations can be applied to more complex systems of collective cell movement without prior knowledge of the cellular machinery and behavioral cues. PMID:28533367

Origins of the elastic behavior of nanoparticle chain aggregates: Measurements using nanostructure manipulation device

NASA Astrophysics Data System (ADS)

Suh, Yong J.; Friedlander, Sheldon K.

2003-03-01

Nanoscale studies were conducted on the dynamic behavior of individual nanoparticle chain aggregates (NCAs) and their networks. For this purpose, device was fabricated to apply tension to NCA under controlled conditions. The device is composed of a specimen support and a cartridge. The specimen support is a deformable alloy disk with a narrow slit across which the NCAs are deposited; the cartridge is used to connect the specimen support to a specimen elongation support holder. The aggregates were stretched using the specimen holder to widen or narrow the slit gap at speeds from 0.5 to 300 nm/s and the motion was observed with a transmission electron microscope. Most of the studies were made with carbon NCA (primary particle size between 11 and 16 nm) generated by laser ablation of a graphite target. The aggregates were deposited on the specimen support (disk) to form bridges across the slit. When tension was applied, the NCA chains remained attached at the slit edges; the chains stretched as kinks on the scale of a few particle diameters were straightened by rotation and/or grain boundary sliding at particle-particle interfaces. After the chain became taut, increasing tension produced little additional extension. Eventually, the chain broke, the tension relaxed, and the elastically strained portions along the NCA recovered. This led to fast contraction of the two broken ends. In one of the cases studied in detail, a small primary particle in the chain doubled in length before the chain broke at this site. This probably occurred because of the high tensile stress in the small particle. In separate experiments, a network of carbon NCA was produced by increased deposition around the slit of a specimen support. Chains in the network broke successively as the network stretched. Some of the chains broke midway and not at the junctures with each other. They contracted fast showing behavior similar to that of the individual aggregates. Possible applications to the behavior of nanocomposite materials composed of blends of NCAs and molecular polymers (e.g., rubber) are described.

Structure and properties of a complex of α-synuclein and a single-domain camelid antibody.

PubMed

De Genst, Erwin J; Guilliams, Tim; Wellens, Joke; O'Day, Elizabeth M; Waudby, Christopher A; Meehan, Sarah; Dumoulin, Mireille; Hsu, Shang-Te Danny; Cremades, Nunilo; Verschueren, Koen H G; Pardon, Els; Wyns, Lode; Steyaert, Jan; Christodoulou, John; Dobson, Christopher M

2010-09-17

The aggregation of the intrinsically disordered protein α-synuclein to form fibrillar amyloid structures is intimately associated with a variety of neurological disorders, most notably Parkinson's disease. The molecular mechanism of α-synuclein aggregation and toxicity is not yet understood in any detail, not least because of the paucity of structural probes through which to study the behavior of such a disordered system. Here, we describe an investigation involving a single-domain camelid antibody, NbSyn2, selected by phage display techniques to bind to α-synuclein, including the exploration of its effects on the in vitro aggregation of the protein under a variety of conditions. We show using isothermal calorimetric methods that NbSyn2 binds specifically to monomeric α-synuclein with nanomolar affinity and by means of NMR spectroscopy that it interacts with the four C-terminal residues of the protein. This latter finding is confirmed by the determination of a crystal structure of NbSyn2 bound to a peptide encompassing the nine C-terminal residues of α-synuclein. The NbSyn2:α-synuclein interaction is mediated mainly by side-chain interactions while water molecules cross-link the main-chain atoms of α-synuclein to atoms of NbSyn2, a feature we believe could be important in intrinsically disordered protein interactions more generally. The aggregation behavior of α-synuclein at physiological pH, including the morphology of the resulting fibrillar structures, is remarkably unaffected by the presence of NbSyn2 and indeed we show that NbSyn2 binds strongly to the aggregated as well as to the soluble forms of α-synuclein. These results give strong support to the conjecture that the C-terminal region of the protein is not directly involved in the mechanism of aggregation and suggest that binding of NbSyn2 could be a useful probe for the identification of α-synuclein aggregation in vitro and possibly in vivo. Copyright © 2010. Published by Elsevier Ltd.

Melittin Aggregation in Aqueous Solutions: Insight from Molecular Dynamics Simulations.

PubMed

Liao, Chenyi; Esai Selvan, Myvizhi; Zhao, Jun; Slimovitch, Jonathan L; Schneebeli, Severin T; Shelley, Mee; Shelley, John C; Li, Jianing

2015-08-20

Melittin is a natural peptide that aggregates in aqueous solutions with paradigmatic monomer-to-tetramer and coil-to-helix transitions. Since little is known about the molecular mechanisms of melittin aggregation in solution, we simulated its self-aggregation process under various conditions. After confirming the stability of a melittin tetramer in solution, we observed—for the first time in atomistic detail—that four separated melittin monomers aggregate into a tetramer. Our simulated dependence of melittin aggregation on peptide concentration, temperature, and ionic strength is in good agreement with prior experiments. We propose that melittin mainly self-aggregates via a mechanism involving the sequential addition of monomers, which is supported by both qualitative and quantitative evidence obtained from unbiased and metadynamics simulations. Moreover, by combining computer simulations and a theory of the electrical double layer, we provide evidence to suggest why melittin aggregation in solution likely stops at the tetramer, rather than forming higher-order oligomers. Overall, our study not only explains prior experimental results at the molecular level but also provides quantitative mechanistic information that may guide the engineering of melittin for higher efficacy and safety.

Molecular chaperone properties of the high molecular weight aggregate from aged lens

NASA Technical Reports Server (NTRS)

Takemoto, L.; Boyle, D.; Spooner, B. S. (Principal Investigator)

1994-01-01

The high molecular weight aggregate (HMWA) fraction was isolated from the water soluble proteins of aged bovine lenses. Its composition and ability to inhibit heat-induced denaturation and aggregation were compared with the lower molecular weight, oligomeric fraction of alpha isolated from the same lens. Although the major components of both fractions were the alpha-A and alpha-B chains, the HMWA fraction possessed a decreased ability to protect other proteins against heat-induced denaturation and aggregation. Immunoelectron microscopy of both fractions demonstrated that alpha particles from the HMWA fraction contained increased amounts of beta and gamma crystallins, bound to a central region of the supramolecular complex. Together, these results demonstrate that alpha crystallins found in the HMWA fraction possess a decreased ability to protect against heat-induced denaturation and aggregation, and suggest that at least part of this decrease could be due to the increased presence of beta and gamma crystallins complexed to the putative chaperone receptor site of the alpha particles.

Membrane Interactions of hIAPP Monomer and Oligomer with Lipid Membranes by Molecular Dynamics Simulations.

PubMed

Zhang, Mingzhen; Ren, Baiping; Liu, Yonglan; Liang, Guizhao; Sun, Yan; Xu, Lijian; Zheng, Jie

2017-08-16

Interaction of human islet amyloid polypeptide (hIAPP) peptides with cell membrane is crucial for the understanding of amyloid toxicity associated with Type II diabetes (T2D). While it is known that the hIAPP-membrane interactions are considered to promote hIAPP aggregation into fibrils and induce membrane disruption, the membrane-induced conformation, orientation, aggregation, and adsorption behaviors of hIAPP peptides have not been well understood at the atomic level. Herein, we perform all-atom explicit-water molecular dynamics (MD) simulations to study the adsorption, orientation, and surface interaction of hIAPP aggregates with different sizes (monomer to tetramer) and conformations (monomer with α-helix and tetramer with β-sheet-rich U-turn) upon adsorption on the lipid bilayers composed of both pure zwitterionic POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and mixed anionic POPC/POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) (3:1) lipids. MD simulation results show that hIAPP monomer with α-helical conformation and hIAPP pentamer with β-sheet conformation can adsorb on both POPC and POPC/POPE bilayers via a preferential orientation of N-terminal residues facing toward the bilayer surface. The hIAPP aggregates show stronger interactions with mixed POPC/POPE lipids than pure POPC lipids, consistent with experimental observation that hIAPP adsorption and fibrililation are enhanced on mixed lipid bilayers. While electrostatic interactions are main attractive forces to drive the hIAPP aggregates to adsorb on both bilayers, the introduction of the more hydrophilic head groups of POPE lipids further promote the formation of the interfacial hydrogen bonds. Complement to our previous studies of hIAPP aggregates in bulk solution, this computational work increases our knowledge about the mechanism of amyloid peptide-membrane interactions that is central to the understanding the progression of all amyloid diseases.

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

PubMed

Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

2016-01-01

Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

Behavioral Phenotyping and Pathological Indicators of Parkinson's Disease in C. elegans Models

PubMed Central

Maulik, Malabika; Mitra, Swarup; Bult-Ito, Abel; Taylor, Barbara E.; Vayndorf, Elena M.

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder with symptoms that progressively worsen with age. Pathologically, PD is characterized by the aggregation of α-synuclein in cells of the substantia nigra in the brain and loss of dopaminergic neurons. This pathology is associated with impaired movement and reduced cognitive function. The etiology of PD can be attributed to a combination of environmental and genetic factors. A popular animal model, the nematode roundworm Caenorhabditis elegans, has been frequently used to study the role of genetic and environmental factors in the molecular pathology and behavioral phenotypes associated with PD. The current review summarizes cellular markers and behavioral phenotypes in transgenic and toxin-induced PD models of C. elegans. PMID:28659967

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the HdhQ150/Q150 Mouse Model of Huntington’s Disease

PubMed Central

Rattray, Ivan; Smith, Edward J.; Crum, William R.; Walker, Thomas A.; Gale, Richard; Bates, Gillian P.

2017-01-01

A variety of mouse models have been developed that express mutant huntingtin (mHTT) leading to aggregates and inclusions that model the molecular pathology observed in Huntington’s disease. Here we show that although homozygous HdhQ150 knock-in mice developed motor impairments (rotarod, locomotor activity, grip strength) by 36 weeks of age, cognitive dysfunction (swimming T maze, fear conditioning, odor discrimination, social interaction) was not evident by 94 weeks. Concomitant to behavioral assessments, T2-weighted MRI volume measurements indicated a slower striatal growth with a significant difference between wild type (WT) and HdhQ150 mice being present even at 15 weeks. Indeed, MRI indicated significant volumetric changes prior to the emergence of the “clinical horizon” of motor impairments at 36 weeks of age. A striatal decrease of 27% was observed over 94 weeks with cortex (12%) and hippocampus (21%) also indicating significant atrophy. A hypothesis-free analysis using tensor-based morphometry highlighted further regions undergoing atrophy by contrasting brain growth and regional neurodegeneration. Histology revealed the widespread presence of mHTT aggregates and cellular inclusions. However, there was little evidence of correlations between these outcome measures, potentially indicating that other factors are important in the causal cascade linking the molecular pathology to the emergence of behavioral impairments. In conclusion, the HdhQ150 mouse model replicates many aspects of the human condition, including an extended pre-manifest period prior to the emergence of motor impairments. PMID:28099507

Crystallography and Molecular Arrangement of Polymorphic Monolayer J-Aggregates of a Cyanine Dye: Multiangle Polarized Light Fluorescence Optical Microscopy Study.

PubMed

Prokhorov, Valery V; Pozin, Sergey I; Perelygina, Olga M; Mal'tsev, Eugene I

2018-04-24

The molecular orientation in monolayer J-aggregates of 3,3-di(γ-sulfopropyl)-5,5-dichlorotiamonomethinecyanine dye has been precisely estimated using improved linear polarization measurements in the fluorescence microscope in which a multiangle set of polarization data is obtained using sample rotation. The estimated molecular orientation supplemented with the previously established crystallographic constraints based on the analysis of the well-developed two-dimensional J-aggregate shapes unambiguously indicate the staircase type of molecular arrangement for striplike J-aggregates with the staircases oriented along strips. The molecular transition dipoles are inclined at an angle of ∼25° to the strip direction, whereas the characteristic strip vertex angle ∼45° is formed by the [100] and [1-10] directions of the monoclinic unit cell. Measurements of the geometry of partially unwound tubes and their polarization properties support the model of tube formation by close-packed helical winding of flexible monolayer strips. In the tubes, the long molecular axes are oriented at a small angle in the range of 5-15° to the normal to the tube axis providing low bending energy. At a nanoscale, high-resolution atomic force microscopy imaging of J-aggregate monolayers reveals a complex quasi-one-dimensional organization.

Molecular Origins of Mesoscale Ordering in a Metalloamphiphile Phase

PubMed Central

2015-01-01

Controlling the assembly of soft and deformable molecular aggregates into mesoscale structures is essential for understanding and developing a broad range of processes including rare earth extraction and cleaning of water, as well as for developing materials with unique properties. By combined synchrotron small- and wide-angle X-ray scattering with large-scale atomistic molecular dynamics simulations we analyze here a metalloamphiphile–oil solution that organizes on multiple length scales. The molecules associate into aggregates, and aggregates flocculate into meso-ordered phases. Our study demonstrates that dipolar interactions, centered on the amphiphile headgroup, bridge ionic aggregate cores and drive aggregate flocculation. By identifying specific intermolecular interactions that drive mesoscale ordering in solution, we bridge two different length scales that are classically addressed separately. Our results highlight the importance of individual intermolecular interactions in driving mesoscale ordering. PMID:27163014

Amyloidogenesis abolished by proline substitutions but enhanced by lipid binding.

PubMed

Jiang, Ping; Xu, Weixin; Mu, Yuguang

2009-04-01

The influence of lipid molecules on the aggregation of a highly amyloidogenic segment of human islet amyloid polypeptide, hIAPP20-29, and the corresponding sequence from rat has been studied by all-atom replica exchange molecular dynamics (REMD) simulations with explicit solvent model. hIAPP20-29 fragments aggregate into partially ordered beta-sheet oligomers and then undergo large conformational reorganization and convert into parallel/antiparallel beta-sheet oligomers in mixed in-register and out-of-register patterns. The hydrophobic interaction between lipid tails and residues at positions 23-25 is found to stabilize the ordered beta-sheet structure, indicating a catalysis role of lipid molecules in hIAPP20-29 self-assembly. The rat IAPP variants with three proline residues maintain unstructured micelle-like oligomers, which is consistent with non-amyloidogenic behavior observed in experimental studies. Our study provides the atomic resolution descriptions of the catalytic function of lipid molecules on the aggregation of IAPP peptides.

Selective aggregation of the splicing factor Hsh155 suppresses splicing upon genotoxic stress.

PubMed

Mathew, Veena; Tam, Annie S; Milbury, Karissa L; Hofmann, Analise K; Hughes, Christopher S; Morin, Gregg B; Loewen, Christopher J R; Stirling, Peter C

2017-12-04

Upon genotoxic stress, dynamic relocalization events control DNA repair as well as alterations of the transcriptome and proteome, enabling stress recovery. How these events may influence one another is only partly known. Beginning with a cytological screen of genome stability proteins, we find that the splicing factor Hsh155 disassembles from its partners and localizes to both intranuclear and cytoplasmic protein quality control (PQC) aggregates under alkylation stress. Aggregate sequestration of Hsh155 occurs at nuclear and then cytoplasmic sites in a manner that is regulated by molecular chaperones and requires TORC1 activity signaling through the Sfp1 transcription factor. This dynamic behavior is associated with intron retention in ribosomal protein gene transcripts, a decrease in splicing efficiency, and more rapid recovery from stress. Collectively, our analyses suggest a model in which some proteins evicted from chromatin and undergoing transcriptional remodeling during stress are targeted to PQC sites to influence gene expression changes and facilitate stress recovery. © 2017 Mathew et al.

Amyloidogenesis Abolished by Proline Substitutions but Enhanced by Lipid Binding

PubMed Central

Jiang, Ping; Xu, Weixin; Mu, Yuguang

2009-01-01

The influence of lipid molecules on the aggregation of a highly amyloidogenic segment of human islet amyloid polypeptide, hIAPP20–29, and the corresponding sequence from rat has been studied by all-atom replica exchange molecular dynamics (REMD) simulations with explicit solvent model. hIAPP20–29 fragments aggregate into partially ordered β-sheet oligomers and then undergo large conformational reorganization and convert into parallel/antiparallel β-sheet oligomers in mixed in-register and out-of-register patterns. The hydrophobic interaction between lipid tails and residues at positions 23–25 is found to stabilize the ordered β-sheet structure, indicating a catalysis role of lipid molecules in hIAPP20–29 self-assembly. The rat IAPP variants with three proline residues maintain unstructured micelle-like oligomers, which is consistent with non-amyloidogenic behavior observed in experimental studies. Our study provides the atomic resolution descriptions of the catalytic function of lipid molecules on the aggregation of IAPP peptides. PMID:19360098

Cellular Models of Aggregation-dependent Template-directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer Disease.

PubMed

Harrington, Charles R; Storey, John M D; Clunas, Scott; Harrington, Kathleen A; Horsley, David; Ishaq, Ahtsham; Kemp, Steven J; Larch, Christopher P; Marshall, Colin; Nicoll, Sarah L; Rickard, Janet E; Simpson, Michael; Sinclair, James P; Storey, Lynda J; Wischik, Claude M

2015-04-24

Alzheimer disease (AD) is a degenerative tauopathy characterized by aggregation of Tau protein through the repeat domain to form intraneuronal paired helical filaments (PHFs). We report two cell models in which we control the inherent toxicity of the core Tau fragment. These models demonstrate the properties of prion-like recruitment of full-length Tau into an aggregation pathway in which template-directed, endogenous truncation propagates aggregation through the core Tau binding domain. We use these in combination with dissolution of native PHFs to quantify the activity of Tau aggregation inhibitors (TAIs). We report the synthesis of novel stable crystalline leucomethylthioninium salts (LMTX®), which overcome the pharmacokinetic limitations of methylthioninium chloride. LMTX®, as either a dihydromesylate or a dihydrobromide salt, retains TAI activity in vitro and disrupts PHFs isolated from AD brain tissues at 0.16 μM. The Ki value for intracellular TAI activity, which we have been able to determine for the first time, is 0.12 μM. These values are close to the steady state trough brain concentration of methylthioninium ion (0.18 μM) that is required to arrest progression of AD on clinical and imaging end points and the minimum brain concentration (0.13 μM) required to reverse behavioral deficits and pathology in Tau transgenic mice. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular dynamics studies of protein folding and aggregation

NASA Astrophysics Data System (ADS)

Ding, Feng

This thesis applies molecular dynamics simulations and statistical mechanics to study: (i) protein folding; and (ii) protein aggregation. Most small proteins fold into their native states via a first-order-like phase transition with a major free energy barrier between the folded and unfolded states. A set of protein conformations corresponding to the free energy barrier, Delta G >> kBT, are the folding transition state ensemble (TSE). Due to their evasive nature, TSE conformations are hard to capture (probability ∝ exp(-DeltaG/k BT)) and characterize. A coarse-grained discrete molecular dynamics model with realistic steric constraints is constructed to reproduce the experimentally observed two-state folding thermodynamics. A kinetic approach is proposed to identify the folding TSE. A specific set of contacts, common to the TSE conformations, is identified as the folding nuclei which are necessary to be formed in order for the protein to fold. Interestingly, the amino acids at the site of the identified folding nuclei are highly conserved for homologous proteins sharing the same structures. Such conservation suggests that amino acids that are important for folding kinetics are under selective pressure to be preserved during the course of molecular evolution. In addition, studies of the conformations close to the transition states uncover the importance of topology in the construction of order parameter for protein folding transition. Misfolded proteins often form insoluble aggregates, amyloid fibrils, that deposit in the extracellular space and lead to a type of disease known as amyloidosis. Due to its insoluble and non-crystalline nature, the aggregation structure and, thus the aggregation mechanism, has yet to be uncovered. Discrete molecular dynamics studies reveal an aggregate structure with the same structural signatures as in experimental observations and show a nucleation aggregation scenario. The simulations also suggest a generic aggregation mechanism that globular proteins under a denaturing environment partially unfold and aggregate by forming stabilizing hydrogen bonds between the backbones of the partial folded substructures. Proteins or peptides rich in alpha-helices also aggregate into beta-rich amyloid fibrils. Upon aggregation, the protein or peptide undergoes a conformational transition from alpha-helices to beta-sheets. The transition of alpha-helix to beta-hairpin (two-stranded beta-sheet) is studied in an all-heavy-atom discrete molecular dynamics model of a polyalanine chain. An entropical driving scenario for the alpha-helix to beta-hairpin transition is discovered.

Structure investigations on assembled astaxanthin molecules

NASA Astrophysics Data System (ADS)

Köpsel, Christian; Möltgen, Holger; Schuch, Horst; Auweter, Helmut; Kleinermanns, Karl; Martin, Hans-Dieter; Bettermann, Hans

2005-08-01

The carotenoid r,r-astaxanthin (3R,3‧R-dihydroxy-4,4‧-diketo-β-carotene) forms different types of aggregates in acetone-water mixtures. H-type aggregates were found in mixtures with a high part of water (e.g. 1:9 acetone-water mixture) whereas two different types of J-aggregates were identified in mixtures with a lower part of water (3:7 acetone-water mixture). These aggregates were characterized by recording UV/vis-absorption spectra, CD-spectra and fluorescence emissions. The sizes of the molecular assemblies were determined by dynamic light scattering experiments. The hydrodynamic diameter of the assemblies amounts 40 nm in 1:9 acetone-water mixtures and exceeds up to 1 μm in 3:7 acetone-water mixtures. Scanning tunneling microscopy monitored astaxanthin aggregates on graphite surfaces. The structure of the H-aggregate was obtained by molecular modeling calculations. The structure was confirmed by calculating the electronic absorption spectrum and the CD-spectrum where the molecular modeling structure was used as input.

Light absorption and plasmon – exciton interaction in three-layer nanorods with a gold core and outer shell composed of molecular J- and H-aggregates of dyes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, B I; Tyshkunova, E S; Kondorskiy, A D

2015-12-31

Optical properties of hybrid rod-like nanoparticles, consisting of a gold core, an intermediate passive organic layer (spacer) and outer layer of ordered molecular cyanine dye aggregates, are experimentally and theoretically investigated. It is shown that these dyes can form not only ordered J-aggregates but also H-aggregates (differing by the packing angle of dye molecules in an aggregate and having other spectral characteristics) in the outer shell of the hybrid nanostructure. Absorption spectra of synthesised three-layer nanorods are recorded, and their sizes are determined. The optical properties of the composite nanostructures under study are found to differ significantly, depending on themore » type of the molecular aggregate formed in the outer shell. The experimental data are quantitatively explained based on computer simulation using the finite-difference time-domain (FDTD) method, and characteristic features of the plasmon – exciton interaction in the systems under study are revealed. (nanophotonics)« less

Simulation study of 2D spectrum of molecular aggregates coupled to correlated vibrations

NASA Astrophysics Data System (ADS)

Abramavicius, Darius; Butkus, Vytautas; Valkunas, Leonas; Mukamel, Shaul

2011-03-01

Oscillatory dynamics of two-dimensional (2D) spectra of photosynthetic pigment-protein complexes raise the questions of how to disentangle various origins of these oscillations, which may include quantum beats, quantum transport, or molecular vibrations. We study the effects of correlated overdamped fluctuations and under-damped vibrations on the 2D spectra of Fenna-Matthews-Olson (FMO) aggregate, which has well-resolved exciton resonances, and a circular porphyrin aggregate (P6), whose absorption shows vibrational progression. We use a generic exciton Hamiltonian coupled to a bath, characterized by a spectral density. Fluctuations have smooth, while vibtations have δ -type spectral densities. We show how various scenarios of correlated molecular fluctuations lead to some highly oscillatory crosspeaks. Molecular vibrations cause progression of diagonal peaks in the 2D spectrum and make their corresponding cross-peaks highly oscillatory. We, thus, demonstrate that bath fluctuations and molecular vibrations of realistic molecular aggregates are highly entangled in 2D spectroscopy. DA acknowledges grant VP1-3.1-SMM-07-V, SM - the grants CHE0745892 (NSF), DRPA BAA-10-40 QUBE.

Rate Kinetics and Molecular Dynamics of the Structural Transitions in Amyloidogenic Proteins

NASA Astrophysics Data System (ADS)

Steckmann, Timothy M.

Amyloid fibril aggregation is associated with several horrific diseases such as Alzheimer's, Creutzfeld-Jacob, diabetes, Parkinson's and others. The process of amyloid aggregation involves forming myriad different metastable intermediate aggregates. Amyloid fibrils are composed of proteins that originate in an innocuous alpha-helix or random-coil structure. The alpha-helices convert their structure to beta-strands that aggregate into beta-sheets, and then into protofibrils, and ultimately into fully formed amyloid fibrils. On the basis of experimental data, I have developed a mathematical model for the kinetics of the reaction pathways and determined rate parameters for peptide secondary structural conversion and aggregation during the entire fibrillogenesis process from random coil to fibrils, including the molecular species that accelerate the conversions. The specific steps of the model and the rate constants that are determined by fitting to experimental data provide insight on the molecular species involved in the fibril formation process. To better understand the molecular basis of the protein structural transitions and aggregation, I report on molecular dynamics (MD) computational studies on the formation of amyloid protofibrillar structures in the small model protein ccbeta, which undergoes many of the structural transitions of the larger, naturally occurring amyloid forming proteins. Two different structural transition processes involving hydrogen bonds are observed for aggregation into fibrils: the breaking of intrachain hydrogen bonds to allow beta-hairpin proteins to straighten, and the subsequent formation of interchain hydrogen bonds during aggregation into amyloid fibrils. For my MD simulations, I found that the temperature dependence of these two different structural transition processes results in the existence of a temperature window that the ccbeta protein experiences during the process of forming protofibrillar structures. Both the mathematical modeling of the kinetics and the MD simulations show that molecular structural heterogeneity is a major factor in the process. The MD simulations also show that intrachain and interchain hydrogen bonds breaking and forming is strongly correlated to the process of amyloid formation.

First-principles calculation of the optical properties of an amphiphilic cyanine dye aggregate.

PubMed

Haverkort, Frank; Stradomska, Anna; de Vries, Alex H; Knoester, Jasper

2014-02-13

Using a first-principles approach, we calculate electronic and optical properties of molecular aggregates of the dye amphi-pseudoisocyanine, whose structures we obtained from molecular dynamics (MD) simulations of the self-aggregation process. Using quantum chemistry methods, we translate the structural information into an effective time-dependent Frenkel exciton Hamiltonian for the dominant optical transitions in the aggregate. This Hamiltonian is used to calculate the absorption spectrum. Detailed analysis of the dynamic fluctuations in the molecular transition energies and intermolecular excitation transfer interactions in this Hamiltonian allows us to elucidate the origin of the relevant time scales; short time scales, on the order of up to a few hundreds of femtoseconds, result from internal motions of the dye molecules, while the longer (a few picosecond) time scales we ascribe to environmental motions. The absorption spectra of the aggregate structures obtained from MD feature a blue-shifted peak compared to that of the monomer; thus, our aggregates can be classified as H-aggregates, although considerable oscillator strength is carried by states along the entire exciton band. Comparison to the experimental absorption spectrum of amphi-PIC aggregates shows that the simulated line shape is too wide, pointing to too much disorder in the internal structure of the simulated aggregates.

Self-Assembly and Drug Release Capacities of Organogels via Some Amide Compounds with Aromatic Substituent Headgroups

PubMed Central

Zhang, Lexin; Jiao, Tifeng; Ma, Kai; Xing, Ruirui; Liu, Yamei; Xiao, Yong; Zhou, Jingxin; Zhang, Qingrui; Peng, Qiuming

2016-01-01

In this work, some amide compounds with different aromatic substituent headgroups were synthesized and their gelation self-assembly behaviors in 22 solvents were characterized as new gelators. The obtained results indicated that the size of aromatic substituent headgroups in molecular skeletons in gelators showed crucial effect in the gel formation and self-assembly behavior of all compounds in the solvents used. Larger aromatic headgroups in molecular structures in the synthesized gelator molecules are helpful to form various gel nanostructures. Morphological investigations showed that the gelator molecules can self-assembly and stack into various organized aggregates with solvent change, such as wrinkle, belt, rod, and lamella-like structures. Spectral characterizations suggested that there existed various weak interactions including π-π stacking, hydrogen bonding, and hydrophobic forces due to aromatic substituent headgroups and alkyl substituent chains in molecular structures. In addition, the drug release capacities experiments demonstrated that the drug release rate in present obtained gels can be tuned by adjusting the concentrations of dye. The present work would open up enormous insight to design and investigate new kind of soft materials with designed molecular structures and tunable drug release performance. PMID:28773663

Dye Aggregation and Complex Formation Effects in 7-(Diethylamino)-coumarin-3-carboxylic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiaogang; Cole, Jacqueline M.; Chow, Philip C. Y.

2014-06-19

7-(Diethylamino)-coumarin-3-carboxylic acid (1) has been used as a laser dye, fluorescent label, and biomedical inhibitor in many different applications. Although this dye is typically used in the solution phase, it is prone to molecular aggregation, resulting in many inconsistent optoelectronic properties being reported in the literature. In this paper, the UV—vis absorption and fluorescence spectra of 1 are investigated in three representative solvents: cyclohexane [nonpolar and non-hydrogen bonding (NHB)], ethanol (moderately polar and hydrogen-bond accepting/donating), and DMSO (strongly polar and hydrogen-bond accepting). These experimental results, in conjunction with (time-dependent) density functional theory (DFT/TDDFT) based quantum calculations, have led to themore » identification of the J-aggregates of 1, and rationalized its different aggregation characteristic in cyclohexane in contrast to that of another similar compound, coumarin 343. We show here that these aggregates are largely responsible for the anomalous optoelectronic properties of this compound. In addition, DFT calculations and 1H NMR spectroscopy measurements suggest that the intramolecular hydrogen bond in 1 could be "opened up" in hydrogen-bond accepting solvents, affording significant molecular conformational changes and complex formation effects. The comprehensive understanding of the molecular aggregation and complex formation mechanisms of 1 acquired through this work forms a foundation for the knowledge-based molecular design of organic dyes with tailored aggregation tendencies or anti-aggregation characteristics to cater for different opapplications.« less

Effects of nanoscale aggregation on mechanical properties and local dynamics of precise acid- and ion-containing polymers

NASA Astrophysics Data System (ADS)

Middleton, Luri Robert

Acid- and ion-containing polymers have interchain interactions that alter polymer behavior at the nano, micro, and bulk length scales. Strong secondary-bonds act as thermo-reversible physical crosslinks between chains which drive self-assembly. Tuning theses interactions can modify bulk polymer properties including stiffness, toughness, melt viscosity, resilience, clarity, abrasion resistance and puncture resistance. Furthermore, understanding and improving the relevant factors that control transport properties would have vast implications on developing solid polymer electrolytes (SPEs) for technologically important applications including water desalination, ion exchange membranes and microelectronics. This thesis explores the structure - processing - morphology - property relationships of acid and ionic functionalized polymers. Improvements in synthetic techniques and advancements in characterization methods have enabled new studies of associating polymer systems. Synthesis of entangled, high molecular weight, linear polyethylene (PE) chains functionalized with interacting pendant groups (acidic or ionic) placed periodically along the polymer backbone represent a new class of associating polymers. These polymers with periodic distributions of acid groups are much more homogenous than the commercially available polymers. Previous studies of these polymers with greater structural homogeneity revealed great variety in morphologies of the nano-aggregated polar groups within the non-polar polymer matrix. This thesis correlated the morphologies with bulk properties through real-time X-ray scattering and tensile deformation at a range of temperatures and sample compositions. New, transient morphologies and hierarchical morphologies were observed which coincided with unusual tensile strain hardening. These results indicate that improvements in synthetic control of polymers can enhance physical properties such as tensile strain-hardening, through cooperative bonding between chains. The structural regularity of precise polyethylenes also enables robust comparisons between experiments and computer simulations. At pico- to nano-seconds time scales and length scales of polymer and aggregate dynamics, neutron scattering and molecular dynamics simulations were combined to extend the knowledge of the molecular-level aggregated polymer dynamics. These experiments provide a baseline for future studies of ion-conduction in associating polymer melts.

Molecular mechanisms of cryoprotection in aqueous proline: light scattering and molecular dynamics simulations.

PubMed

Troitzsch, R Z; Vass, H; Hossack, W J; Martyna, G J; Crain, J

2008-04-10

Free proline amino acid is a natural cryoprotectant expressed by numerous organisms under low-temperature stress. Previous reports have suggested that complex assemblies underlie its functional properties. We investigate here aqueous proline solutions as a function of temperature using combinations of Raman spectroscopy, Rayleigh-Brillouin light scattering, and molecular dynamics simulations with the view to revealing the molecular origins of the mixtures' functionality as a cryoprotectant. The evolution of the Brillouin frequency shifts and line widths with temperature shows that, above a critical proline concentration, the water-like dynamics is suppressed and viscoelastic behavior emerges: Here, the Landau-Placzek ratio also shows a temperature-independent maximum arising from concentration fluctuations. Molecular dynamics simulations reveal that the water-water correlations in the mixtures depend much more weakly on temperature than does bulk water. By contrast, the water OH Raman bands exhibit strong red-shifts on cooling similar to those seen in ices; however, no evidence of ice lattice phonons is observed in the low-frequency spectrum. We attribute this primarily to enhanced proline-water hydrogen bonding. In general, the picture that emerges is that aqueous proline is a heterogeneous mixture on molecular length scales (characterized by significant concentration fluctuations rather than well-defined aggregates). Simulations reveal that proline also appears to suppress the normal dependence of water structure on temperature and preserves the ambient-temperature correlations even in very cold solutions. The water structure in cold proline solutions therefore appears to be similar to that at a higher effective temperature. This, coupled with the emergence of glassy dynamics offers a molecular explanation for the functional properties of proline as a cryoprotectant without the need to invoke previously proposed complex aggregates.

The indole compound NC009-1 inhibits aggregation and promotes neurite outgrowth through enhancement of HSPB1 in SCA17 cells and ameliorates the behavioral deficits in SCA17 mice.

PubMed

Chen, Chiung-Mei; Chen, Wan-Ling; Hung, Chen-Ting; Lin, Te-Hsien; Chao, Chih-Ying; Lin, Chih-Hsin; Wu, Yih-Ru; Chang, Kuo-Hsuan; Yao, Ching-Fa; Lee-Chen, Guey-Jen; Su, Ming-Tsan; Hsieh-Li, Hsiu Mei

2018-06-21

Spinocerebellar ataxia type 17 (SCA17) is caused by the expansion of translated CAG repeat in the TATA box binding protein (TBP) gene encoding a long polyglutamine (polyQ) tract in the TBP protein, which leads to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On cells with inducible SCA17 TBP/Q 79 -GFP expression to test five in-house NC009 indole compounds for neuroprotection. We found that both aggregation and polyQ-induced reactive oxygen species can be significantly prohibited by the tested NC009 compounds in Tet-On TBP/Q 79 293 cells. Among the five indole compounds, NC009-1 up-regulated expression of heat shock protein family B (small) member 1 (HSPB1) chaperone to reduce polyQ aggregation and promote neurite outgrowth in neuronal differentiated TBP/Q 79 SH-SY5Y cells. The increased HSPB1 thus ameliorated the increased BH3 interacting domain death agonist (BID), cytochrome c (CYCS) release, and caspase 3 (CASP3) activation which result in apoptosis. Knock down of HSPB1 attenuated the effects of NC009-1 on TBP/Q 79 SH-SY5Y cells, suggesting that HSPB1 might be one of the major pathways involved for NC009-1 effects. NC009-1 further reduced polyQ aggregation in Purkinje cells and ameliorated behavioral deficits in SCA17 TBP/Q 109 transgenic mice. Our results suggest that NC009-1 has a neuroprotective effect on SCA17 cell and mouse models to support its therapeutic potential in SCA17 treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of water-insoluble nonionic copolymer E(6)P(39)E(6) on the microstructure and self-aggregation dynamics of aqueous SDS solution-NMR and SANS investigations.

PubMed

Prameela, G K S; Phani Kumar, B V N; Aswal, V K; Mandal, Asit Baran

2013-10-28

The influence of water-insoluble nonionic triblock copolymer PEO-PPO-PEO [poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)] i.e., E6P39E6 with molecular weight 2800, on the microstructure and self-aggregation dynamics of anionic surfactant sodium dodecylsulfate (SDS) in aqueous solution (D2O) were investigated using high resolution nuclear magnetic resonance (NMR) and small-angle neutron scattering (SANS) measurements. Variable concentration and temperature proton ((1)H), carbon ((13)C) NMR chemical shifts, (1)H self-diffusion coefficients, (1)H spin-lattice and spin-spin relaxation rates data indicate that the higher hydrophobic nature of copolymer significantly influenced aggregation characteristics of SDS. The salient features of the NMR investigations include (i) the onset of mixed micelles at lower SDS concentrations (<3 mM) relative to the copolymer-free case and their evolution into SDS free micelles at higher SDS concentrations (~30 mM), (ii) disintegration of copolymer-SDS mixed aggregate at moderate SDS concentrations (~10 mM) and still binding of a copolymer with SDS and (iii) preferential localization of the copolymer occurred at the SDS micelle surface. SANS investigations indicate prolate ellipsoidal shaped mixed aggregates with an increase in SDS aggregation number, while a contrasting behavior in the copolymer aggregation is observed. The aggregation features of SDS and the copolymer, the sizes of mixed aggregates and the degree of counterion dissociation (α) extracted from SANS data analysis corroborate reasonably well with those of (1)H NMR self-diffusion and sodium ((23)Na) spin-lattice relaxation data.

Molecular aggregation of humic substances

USGS Publications Warehouse

Wershaw, R. L.

1999-01-01

Humic substances (HS) form molecular aggregates in solution and on mineral surfaces. Elucidation of the mechanism of formation of these aggregates is important for an understanding of the interactions of HS in soils arid natural waters. The HS are formed mainly by enzymatic depolymerization and oxidation of plant biopolymers. These reactions transform the aromatic and lipid plant components into amphiphilic molecules, that is, molecules that consist of separate hydrophobic (nonpolar) and hydrophilic (polar) parts. The nonpolar parts of the molecules are composed of relatively unaltered segments of plant polymers and the polar parts of carboxylic acid groups. These amphiphiles form membrane-like aggregates on mineral surfaces and micelle-like aggregates in solution. The exterior surfaces of these aggregates are hydrophilic, and the interiors constitute separate hydrophobic liquid-like phases.

Nanoparticle-mediated local and remote manipulation of protein aggregation.

PubMed

Kogan, Marcelo J; Bastus, Neus G; Amigo, Roger; Grillo-Bosch, Dolors; Araya, Eyleen; Turiel, Antonio; Labarta, Amilcar; Giralt, Ernest; Puntes, Victor F

2006-01-01

The local heat delivered by metallic nanoparticles selectively attached to their target can be used as a molecular surgery to safely remove toxic and clogging aggregates. We apply this principle to protein aggregates, in particular to the amyloid beta protein (Abeta) involved in Alzheimer's disease (AD), a neurodegenerative disease where unnaturally folded Abeta proteins self-assemble and deposit forming amyloid fibrils and plaques. We show the possibility to remotely redissolve these deposits and to interfere with their growth, using the local heat dissipated by gold nanoparticles (AuNP) selectively attached to the aggregates and irradiated with low gigahertz electromagnetic fields. Simultaneous tagging and manipulation by AuNP of Abeta at different stages of aggregation allow both, noninvasive exploration and dissolution of molecular aggregates.

Initial stages of aggregation in aqueous solutions of ionic liquids: molecular dynamics studies.

PubMed

Bhargava, B L; Klein, Michael L

2009-07-16

Structures formed by 1-alkyl-3-methylimidazolium bromide aqueous solutions with decyl, dodecyl, tetradecyl, and hexadecyl chains have been studied using molecular dynamics (MD) simulations. Spontaneous self-assembly of the amphiphilic cations to form quasi-spherical polydisperse aggregates has been observed in all of the systems, with the size and nature of the aggregates varying with chain length. In all systems, the cation alkyl tails are buried deep inside the aggregates with the polar imidazolium group exposed to exploit the favorable interactions with water. Aggregation numbers steadily increase with the chain length. The hexadecyl aggregates have the most ordered internal structure of the systems studied, and the alkyl chains in these cations show the least number of gauche defects.

Optical characteristics of the nanoparticle coupled to a quantum molecular aggregate

NASA Astrophysics Data System (ADS)

Ropakova, I. Yu.; Zvyagin, A. A.

2017-11-01

Optical characteristics of a single nanoparticle, coupled to the one-dimensional quantum molecular aggregate is studied. Depending on the values of the coupling of the particle and its own frequency, with respect to the own frequency of the aggregated molecules, and the strength of the aggregation, the dynamical relative permittivity of the nanoparticle manifests the contribution from the exciton band, or/and the ones from the local level(s) caused by the particle. The refractive index and the extinction coefficient of the nanoparticle is also calculated.

Aggregating indices of risk and protection for adolescent behavior problems: the Communities That Care Youth Survey.

PubMed

Feinberg, Mark E; Ridenour, Ty A; Greenberg, Mark T

2007-06-01

To facilitate research on adolescent risk and protection regarding behavior problems, and to facilitate community decision-making regarding resource allocation for intervention programs, by creating a reduced set of coherent aggregate indices of adolescent risk and protection. We examined the 31 risk and protective factor scales in the Communities That Care Youth Survey (CTC-YS). Data came from two waves of the CTC-YS administered to sixth through 12th graders in Pennsylvania (2001 n = 43,842; 2003 n =101,988). Factor analysis and calculation of internal reliability were used to create aggregate indices of risk/protective factor domains. Correlations of aggregate indices with each other and with problem behaviors (antisocial behavior, substance use) were examined. Theory and empirical results led to the creation of seven coherent indices: Community Cohesion, Family Cohesion, Family Risk, School Support for Prosocial Activities, Antisocial Peer Domain, Attitudes toward Risky Behavior, Risky Behavioral Tendencies. Four scales were not included in the aggregate index (Religiosity, Academic Performance, Personal Transitions and Mobility, and Early Initiation of Drug Use and Antisocial Behavior). The indices were related to each other and to adolescent problem behaviors (antisocial behavior and substance use) in expected ways. Results were consistent across waves of data. The construction of theoretically meaningful and empirically defensible aggregate measures of adolescent risk and protective factors is possible, although analyses of other data sets and further discussion are warranted. The use of aggregate indices by researchers and communities is recommended as a way to facilitate research and decision-making.

Characterization of Nanoparticle Aggregation in Biologically Relevant Fluids

NASA Astrophysics Data System (ADS)

McEnnis, Kathleen; Lahann, Joerg

Nanoparticles (NPs) are often studied as drug delivery vehicles, but little is known about their behavior in blood once injected into animal models. If the NPs aggregate in blood, they will be shunted to the liver or spleen instead of reaching the intended target. The use of animals for these experiments is costly and raises ethical questions. Typically dynamic light scattering (DLS) is used to analyze aggregation behavior, but DLS cannot be used because the components of blood also scatter light. As an alternative, a method of analyzing NPs in biologically relevant fluids such as blood plasma has been developed using nanoparticle tracking analysis (NTA) with fluorescent filters. In this work, NTA was used to analyze the aggregation behavior of fluorescent polystyrene NPs with different surface modifications in blood plasma. It was expected that different surface chemistries on the particles will change the aggregation behavior. The effect of the surface modifications was investigated by quantifying the percentage of NPs in aggregates after addition to blood plasma. The use of this characterization method will allow for better understanding of particle behavior in the body, and potential problems, specifically aggregation, can be addressed before investing in in vivo studies.

Effect of some aggregate characteristics on the fatigue behavior of an asphaltic concrete mixture.

DOT National Transportation Integrated Search

1970-01-01

The effect of aggregate characteristics on the fatigue behavior of asphaltic mixtures was investigated by utilizing a laboratory constant deflection, flexural fatigue test. Coarse aggregate characteristics such as surface texture, rugosity, and flaki...

Numerical investigation of aggregated fuel spatial pattern impacts on fire behavior

DOE PAGES

Parsons, Russell A.; Linn, Rodman Ray; Pimont, Francois; ...

2017-06-18

Here, landscape heterogeneity shapes species distributions, interactions, and fluctuations. Historically, in dry forest ecosystems, low canopy cover and heterogeneous fuel patterns often moderated disturbances like fire. Over the last century, however, increases in canopy cover and more homogeneous patterns have contributed to altered fire regimes with higher fire severity. Fire management strategies emphasize increasing within-stand heterogeneity with aggregated fuel patterns to alter potential fire behavior. Yet, little is known about how such patterns may affect fire behavior, or how sensitive fire behavior changes from fuel patterns are to winds and canopy cover. Here, we used a physics-based fire behavior model,more » FIRETEC, to explore the impacts of spatially aggregated fuel patterns on the mean and variability of stand-level fire behavior, and to test sensitivity of these effects to wind and canopy cover. Qualitative and quantitative approaches suggest that spatial fuel patterns can significantly affect fire behavior. Based on our results we propose three hypotheses: (1) aggregated spatial fuel patterns primarily affect fire behavior by increasing variability; (2) this variability should increase with spatial scale of aggregation; and (3) fire behavior sensitivity to spatial pattern effects should be more pronounced under moderate wind and fuel conditions.« less

Numerical investigation of aggregated fuel spatial pattern impacts on fire behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parsons, Russell A.; Linn, Rodman Ray; Pimont, Francois

Here, landscape heterogeneity shapes species distributions, interactions, and fluctuations. Historically, in dry forest ecosystems, low canopy cover and heterogeneous fuel patterns often moderated disturbances like fire. Over the last century, however, increases in canopy cover and more homogeneous patterns have contributed to altered fire regimes with higher fire severity. Fire management strategies emphasize increasing within-stand heterogeneity with aggregated fuel patterns to alter potential fire behavior. Yet, little is known about how such patterns may affect fire behavior, or how sensitive fire behavior changes from fuel patterns are to winds and canopy cover. Here, we used a physics-based fire behavior model,more » FIRETEC, to explore the impacts of spatially aggregated fuel patterns on the mean and variability of stand-level fire behavior, and to test sensitivity of these effects to wind and canopy cover. Qualitative and quantitative approaches suggest that spatial fuel patterns can significantly affect fire behavior. Based on our results we propose three hypotheses: (1) aggregated spatial fuel patterns primarily affect fire behavior by increasing variability; (2) this variability should increase with spatial scale of aggregation; and (3) fire behavior sensitivity to spatial pattern effects should be more pronounced under moderate wind and fuel conditions.« less

Effects of Phytoplankton Growth Phase on Delayed Settling Behavior of Marine Snow Aggregates at Sharp Density Transitions

NASA Astrophysics Data System (ADS)

Proctor, K. W.; Montgomery, Q. W.; Prairie, J. C.

2016-02-01

Marine snow aggregates play a fundamental role in the marine carbon cycle. Since marine snow aggregates are larger and thus sink faster than individual phytoplankton, aggregates often dominate carbon flux. Previous studies have shown that marine snow aggregates will significantly decrease their settling velocity when passing through sharp density transitions within the ocean, a phenomenon defined as delayed settling. Given the importance of aggregate settling to carbon export, these small-scale changes in aggregate settling dynamics may have significant impacts on the efficiency of the biological pump. However, there is still a lack of knowledge about how different physical properties of aggregates can affect this delayed settling. In this study, we investigated the effect of phytoplankton growth phase on delayed settling behavior. Using phytoplankton cultures stopped at four different growth phases, we formed marine snow aggregates in the laboratory in rotating cylindrical tanks. We then observed individual aggregates as they settled through a stratified tank. We will present data which illustrates that aggregates experience greatly reduced settling rates when passing through sharp density gradients and that the growth phase of the phytoplankton used to form these aggregates has a significant effect on this delayed settling behavior. A thorough understanding of the impact of phytoplankton growth phase on the delayed settling behavior of marine snow will offer insight into the way phytoplankton growth phase may influence the efficiency of the biological pump, carbon flux, and the carbon cycle as a whole.

Numerical studies from quantum to macroscopic scales of carbon nanoparticules in hydrogen plasma

NASA Astrophysics Data System (ADS)

Lombardi, Guillaume; Ngandjong, Alain; Mezei, Zsolt; Mougenot, Jonathan; Michau, Armelle; Hassouni, Khaled; Seydou, Mahamadou; Maurel, François

2016-09-01

Dusty plasmas take part in large scientific domains from Universe Science to nanomaterial synthesis processes. They are often generated by growth from molecular precursor. This growth leads to the formation of larger clusters which induce solid germs nucleation. Particle formed are described by an aerosol dynamic taking into account coagulation, molecular deposition and transport processes. These processes are controlled by the elementary particle. So there is a strong coupling between particle dynamics and plasma discharge equilibrium. This study is focused on the development of a multiscale physic and numeric model of hydrogen plasmas and carbon particles around three essential coupled axes to describe the various physical phenomena: (i) Macro/mesoscopic fluid modeling describing in an auto-coherent way, characteristics of the plasma, molecular clusters and aerosol behavior; (ii) the classic molecular dynamics offering a description to the scale molecular of the chains of chemical reactions and the phenomena of aggregation; (iii) the quantum chemistry to establish the activation barriers of the different processes driving the nanopoarticule formation.

Effects of functional groups and ionization on the structure of alkanethiol coated gold nanoparticles

NASA Astrophysics Data System (ADS)

Bolintineanu, Dan S.; Lane, J. Matthew D.; Grest, Gary S.

2013-03-01

We report fully atomistic molecular dynamics simulations of alkanethiol coated gold nanoparticles solvated in water and decane. The structure of the coatings is analyzed as a function of various functional end groups, including amine and carboxyl groups in different neutralization states. We study the effects of charge in the end groups for two different chain lengths (10 and 18 carbons) and different counterions (mono- and divalent). For the longer alkanes we find significant local phase segregation of chains on the nanoparticle surface, which results in highly asymmetric coating structures. In general, the charged end groups attenuate this effect by enhancing the water solubility of the nanoparticles. Based on the coating structures and density profiles, we can qualitatively infer the overall solubility of the nanoparticles. The asymmetry in the alkanethiol coatings is also likely to have a significant effect on aggregation behavior. More importantly, our simulations suggest the ability to modulate end group charge states (e.g. by changing the pH of the solution) in order to control coating structure, and therefore control solubility and aggregation behavior.

Experimental-Theoretical Approach to the Adsorption Mechanisms for Anionic, Cationic, and Zwitterionic Surfactants at the Calcite-Water Interface.

PubMed

Durán-Álvarez, Agustín; Maldonado-Domínguez, Mauricio; González-Antonio, Oscar; Durán-Valencia, Cecilia; Romero-Ávila, Margarita; Barragán-Aroche, Fernando; López-Ramírez, Simón

2016-03-22

The adsorption of surfactants (DTAB, SDS, and CAPB) at the calcite-water interface was studied through surface zeta potential measurements and multiscale molecular dynamics. The ground-state polarization of surfactants proved to be a key factor for the observed behavior; correlation was found between adsorption and the hard or soft charge distribution of the amphiphile. SDS exhibits a steep aggregation profile, reaching saturation and showing classic ionic-surfactant behavior. In contrast, DTAB and CAPB featured diversified adsorption profiles, suggesting interplay between supramolecular aggregation and desorption from the solid surface and alleviating charge buildup at the carbonate surface when bulk concentration approaches CMC. This manifests as an adsorption profile with a fast initial step, followed by a metastable plateau and finalizing with a sharp decrease and stabilization of surface charge. Suggesting this competition of equilibria, elicited at the CaCO3 surface, this study provides atomistic insight into the adsorption mechanism for ionic surfactants on calcite, which is in accordance with experimental evidence and which is a relevant criterion for developing enhanced oil recovery processes.

Surface properties of heat-induced soluble soy protein aggregates of different molecular masses.

PubMed

Guo, Fengxian; Xiong, Youling L; Qin, Fang; Jian, Huajun; Huang, Xiaolin; Chen, Jie

2015-02-01

Suspensions (2% and 5%, w/v) of soy protein isolate (SPI) were heated at 80, 90, or 100 °C for different time periods to produce soluble aggregates of different molecular sizes to investigate the relationship between particle size and surface properties (emulsions and foams). Soluble aggregates generated in these model systems were characterized by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Heat treatment increased surface hydrophobicity, induced SPI aggregation via hydrophobic interaction and disulfide bonds, and formed soluble aggregates of different sizes. Heating of 5% SPI always promoted large-size aggregate (LA; >1000 kDa) formation irrespective of temperature, whereas the aggregate size distribution in 2% SPI was temperature dependent: the LA fraction progressively rose with temperature (80→90→100 °C), corresponding to the attenuation of medium-size aggregates (MA; 670 to 1000 kDa) initially abundant at 80 °C. Heated SPI with abundant LA (>50%) promoted foam stability. LA also exhibited excellent emulsifying activity and stabilized emulsions by promoting the formation of small oil droplets covered with a thick interfacial protein layer. However, despite a similar influence on emulsion stability, MA enhanced foaming capacity but were less capable of stabilizing emulsions than LA. The functionality variation between heated SPI samples is clearly related to the distribution of aggregates that differ in molecular size and surface activity. The findings may encourage further research to develop functional SPI aggregates for various commercial applications. © 2015 Institute of Food Technologists®

Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths.

PubMed Central

Snyder, S W; Ladror, U S; Wade, W S; Wang, G T; Barrett, L W; Matayoshi, E D; Huffaker, H J; Krafft, G A; Holzman, T F

1994-01-01

One of the clinical manifestations of Alzheimer's disease is the deposition of the 39-43 residue amyloid-beta (A beta) peptide in aggregated fibrils in senile plaques. Characterization of the aggregation behavior of A beta is one of the critical issues in understanding the role of A beta in the disease process. Using solution hydrodynamics, A beta was observed to form three types of species in phosphate-buffered saline: insoluble aggregates with sedimentation coefficients of approximately 50,000 S and molecular masses of approximately 10(9) Da, "soluble aggregates" with sedimentation coefficients of approximately 30 S and masses of approximately 10(6) Da, and monomer. When starting from monomer, the aggregation kinetics of A beta 1-40 (A beta 40) and A beta 1-42 (A beta 42), alone and in combination, reveal large differences in the tendency of these peptides to aggregate as a function of pH and other solution conditions. At pH 4.1 and 7.0-7.4, aggregation is significantly slower than at pH 5 and 6. Under all conditions, aggregation of the longer A beta 42 was more rapid than A beta 40. Oxidation of Met-35 to the sulfoxide in A beta 40 enhances the aggregation rate over that of the nonoxidized peptide. Aggregation was found to be dependent upon temperature and to be strongly dependent on peptide concentration and ionic strength, indicating that aggregation is driven by a hydrophobic effect. When A beta 40 and A beta 42 are mixed together, A beta 40 retards the aggregation of A beta 42 in a concentration-dependent manner. Shorter fragments have a decreasing ability to interfere with A beta 42 aggregation. Conversely, the rate of aggregation of A beta 40 can be significantly enhanced by seeding slow aggregating solutions with preformed aggregates of A beta 42. Taken together, the inhibition of A beta 42 aggregation by A beta 40, the seeding of A beta 40 aggregation by A beta 42 aggregates, and the chemical oxidation of A beta 40 suggest that the relative abundance and rates of production of different-length A beta and its exposure to radical damage may be factors in the accumulation of A beta in plaques in vivo. Images FIGURE 6 PMID:7811936

Environment‐Adaptive Coassembly/Self‐Sorting and Stimulus‐Responsiveness Transfer Based on Cholesterol Building Blocks

PubMed Central

Xing, Pengyao; Tham, Huijun Phoebe; Li, Peizhou; Chen, Hongzhong; Xiang, Huijing

2017-01-01

Abstract Manipulating the property transfer in nanosystems is a challenging task since it requires switchable molecular packing such as separate aggregation (self‐sorting) or synergistic aggregation (coassembly). Herein, a unique manipulation of self‐sorting/coassembly aggregation and the observation of switchable stimulus‐responsiveness transfer in a two component self‐assembly system are reported. Two building blocks bearing the same cholesterol group give versatile topological structures in polar and nonpolar solvents. One building block (cholesterol conjugated cynanostilbene, CCS) consists of cholesterol conjugated with a cynanostilbene unit, and the other one (C10CN) is comprised of cholesterol connected with a naphthalimide group having a flexible long alkyl chain. Their assemblies including gel, crystalline plates, and vesicles are obtained. In gel and crystalline plate phases, the self‐sorting behavior dominates, while synergistic coassembly occurs in vesicle phase. Since CCS having the cyanostilbene group can respond to the light irradiation, it undergoes light‐induced chiral amplification. C10CN is thermally responsive, whereby its supramolecular chirality is inversed upon heating. In coassembled vesicles, it is interestingly observed that their responsiveness can be transferred by each other, i.e., the C10CN segment is sensitive to the light irradiation, while CCS is thermoresponsive. This unprecedented behavior of the property transfer may shine a light to the precise fabrication of smart materials. PMID:29375976

Vapor-pressure osmometric study of the molecular weight and aggregation tendency of a reference-soil fulvic acid

USGS Publications Warehouse

Marinsky, J.A.; Reddy, M.M.

1990-01-01

The molecular weight and aggregation tendency of a reference-soil fulvic acid in Armadale horizon Bh were determined by vapor-pressure osmometry using tetrahydrofuran and water as solvents. With tetrahydrofuran, number-average molecular weight values of 767 ?? 34 and 699 ?? 8 daltons were obtained from two separate sets of measurements. Two sets of measurements with water also yielded values within this range (754 ?? 70 daltons) provided that the fulvic acid concentration in water did not exceed 7 mg ml-1; at higher concentrations (9.1-13.7 mg ml-1) a number-average molecular weight of 956 ?? 25 daltons was resolved, providing evidence of molecular aggregation. Extension of these studies to 80% neutralized fulvic acid showed that a sizeable fraction of the sodium counter ion is not osmotically active.

SPATIAL AGGREGATION IN A FOREST FLOOR INSECT DEPENDS ON SEASONAL CONGREGATION AND SCATTERING EFFECTS OF PREDATORS

EPA Science Inventory

Spatial aggregations arising from gregarious behavior are common in nature and have important implications for population dynamics, community stability, and conservation. However, the translation of aggregation behaviors into emergent properties of populations and communities de...

Hierarchical charge distribution controls self-assembly process of silk in vitro

NASA Astrophysics Data System (ADS)

Zhang, Yi; Zhang, Cencen; Liu, Lijie; Kaplan, David L.; Zhu, Hesun; Lu, Qiang

2015-12-01

Silk materials with different nanostructures have been developed without the understanding of the inherent transformation mechanism. Here we attempt to reveal the conversion road of the various nanostructures and determine the critical regulating factors. The regulating conversion processes influenced by a hierarchical charge distribution were investigated, showing different transformations between molecules, nanoparticles and nanofibers. Various repulsion and compressive forces existed among silk fibroin molecules and aggregates due to the exterior and interior distribution of charge, which further controlled their aggregating and deaggregating behaviors and finally formed nanofibers with different sizes. Synergistic action derived from molecular mobility and concentrations could also tune the assembly process and final nanostructures. It is suggested that the complicated silk fibroin assembly processes comply a same rule based on charge distribution, offering a promising way to develop silk-based materials with designed nanostructures.

Aggregation-Induced Emission (AIE) Fluorophore Exhibits a Highly Ratiometric Fluorescent Response to Zn2+ in vitro and in Human Liver Cancer Cells.

PubMed

Mehdi, Hassan; Gong, Weitao; Guo, Huimin; Watkinson, Michael; Ma, Hua; Wajahat, Ali; Ning, Guiling

2017-09-21

Two novel organic fluorophores, containing bis-naphthylamide and quinoline motifs, have been designed and synthesized. One of the fluorophores contains an isobutylene unit and exhibits a significant aggregation-induced emission (AIE) and a remarkable highly selective ratiometric fluorescence response towards Zn 2+ in solution as well as in human liver cancer cells. The AIE behavior of this fluorophore was fully verified by fluorescence and UV/Vis spectroscopy, quantum yield calculations, and single-crystal X-ray diffraction, which revealed an intricate crystal packing system. Conversely, a fluorophore that lacks the isobutylene moiety did not exhibit any significant fluorescent properties as a result of its more flexible molecular structure that presumably allows free intramolecular rotational processes to occur. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reduction of the 3,4,9,10-perylenediimides and the formation of eletrodeposited films based on their radical anions

NASA Astrophysics Data System (ADS)

Zhu, Yuan-Yuan; Gu, Shuang-Xi

2014-09-01

The reduction of the two 3,4,9,10-perylene diimide (PDI) derivatives in the mixture of hydrazine hydrate and N,N-dimethylformamide was investigated by the UV-vis absorption spectra, fluorescence spectra (FL) and electron spin resonance spectroscopy (ESR). The time dependence of the PDI content, as well as the structure of PDI aggregates were also investigated and discussed. Combining the electro-migration behavior of PDI-· with the molecular self-assembly properties, the films of two PDI derivatives (PDI-32 and PDI-123) were successfully fabricated via anode electro-deposition (AED). The difference of aggregation state between the two PDI films was studied by UV-vis absorption spectra, XRD and SEM. Based on these, the formation mechanism of PDI films was also deduced.

Statistical physics approaches to Alzheimer's disease

NASA Astrophysics Data System (ADS)

Peng, Shouyong

Alzheimer's disease (AD) is the most common cause of late life dementia. In the brain of an AD patient, neurons are lost and spatial neuronal organizations (microcolumns) are disrupted. An adequate quantitative analysis of microcolumns requires that we automate the neuron recognition stage in the analysis of microscopic images of human brain tissue. We propose a recognition method based on statistical physics. Specifically, Monte Carlo simulations of an inhomogeneous Potts model are applied for image segmentation. Unlike most traditional methods, this method improves the recognition of overlapped neurons, and thus improves the overall recognition percentage. Although the exact causes of AD are unknown, as experimental advances have revealed the molecular origin of AD, they have continued to support the amyloid cascade hypothesis, which states that early stages of aggregation of amyloid beta (Abeta) peptides lead to neurodegeneration and death. X-ray diffraction studies reveal the common cross-beta structural features of the final stable aggregates-amyloid fibrils. Solid-state NMR studies also reveal structural features for some well-ordered fibrils. But currently there is no feasible experimental technique that can reveal the exact structure or the precise dynamics of assembly and thus help us understand the aggregation mechanism. Computer simulation offers a way to understand the aggregation mechanism on the molecular level. Because traditional all-atom continuous molecular dynamics simulations are not fast enough to investigate the whole aggregation process, we apply coarse-grained models and discrete molecular dynamics methods to increase the simulation speed. First we use a coarse-grained two-bead (two beads per amino acid) model. Simulations show that peptides can aggregate into multilayer beta-sheet structures, which agree with X-ray diffraction experiments. To better represent the secondary structure transition happening during aggregation, we refine the model to four beads per amino acid. Typical essential interactions, such as backbone hydrogen bond, hydrophobic and electrostatic interactions, are incorporated into our model. We study the aggregation of Abeta16-22, a peptide that can aggregate into a well-ordered fibrillar structure in experiments. Our results show that randomly-oriented monomers can aggregate into fibrillar subunits, which agree not only with X-ray diffraction experiments but also with solid-state NMR studies. Our findings demonstrate that coarse-grained models and discrete molecular dynamics simulations can help researchers understand the aggregation mechanism of amyloid peptides.

Effects of Polymer Hydrophobicity on Protein Structure and Aggregation Kinetics in Crowded Milieu.

PubMed

Breydo, Leonid; Sales, Amanda E; Frege, Telma; Howell, Mark C; Zaslavsky, Boris Y; Uversky, Vladimir N

2015-05-19

We examined the effects of water-soluble polymers of various degrees of hydrophobicity on the folding and aggregation of proteins. The polymers we chose were polyethylene glycol (PEG) and UCON (1:1 copolymer of ethylene glycol and propylene glycol). The presence of additional methyl groups in UCON makes it more hydrophobic than PEG. Our earlier analysis revealed that similarly sized PEG and UCON produced different changes in the solvent properties of water in their solutions and induced morphologically different α-synuclein aggregates [Ferreira, L. A., et al. (2015) Role of solvent properties of aqueous media in macromolecular crowding effects. J. Biomol. Struct. Dyn., in press]. To improve our understanding of molecular mechanisms defining behavior of proteins in a crowded environment, we tested the effects of these polymers on secondary and tertiary structure and aromatic residue solvent accessibility of 10 proteins [five folded proteins, two hybrid proteins; i.e., protein containing ordered and disordered domains, and three intrinsically disordered proteins (IDPs)] and on the aggregation kinetics of insulin and α-synuclein. We found that effects of both polymers on secondary and tertiary structures of folded and hybrid proteins were rather limited with slight unfolding observed in some cases. Solvent accessibility of aromatic residues was significantly increased for the majority of the studied proteins in the presence of UCON but not PEG. PEG also accelerated the aggregation of protein into amyloid fibrils, whereas UCON promoted aggregation to amyloid oligomers instead. These results indicate that even a relatively small change in polymer structure leads to a significant change in the effect of this polymer on protein folding and aggregation. This is an indication that protein folding and especially aggregation are highly sensitive to the presence of other macromolecules, and an excluded volume effect is insufficient to describe their effect.

Optical spectroscopy and system-bath interactions in molecular aggregates with full configuration interaction Frenkel exciton model

NASA Astrophysics Data System (ADS)

Seibt, Joachim; Sláma, Vladislav; Mančal, Tomáš

2016-12-01

Standard application of the Frenkel exciton model neglects resonance coupling between collective molecular aggregate states with different number of excitations. These inter-band coupling terms are, however, of the same magnitude as the intra-band coupling between singly excited states. We systematically derive the Frenkel exciton model from quantum chemical considerations, and identify it as a variant of the configuration interaction method. We discuss all non-negligible couplings between collective aggregate states, and provide compact formulae for their calculation. We calculate absorption spectra of molecular aggregate of carotenoids and identify significant band shifts as a result of inter-band coupling. The presence of inter-band coupling terms requires renormalization of the system-bath coupling with respect to standard formulation, but renormalization effects are found to be weak. We present detailed discussion of molecular dimer and calculate its time-resolved two-dimensional Fourier transformed spectra to find weak but noticeable effects of peak amplitude redistribution due to inter-band coupling.

Study on Effects of Different Replacement Rate on Bending Behavior of Big Recycled Aggregate Self Compacting Concrete

NASA Astrophysics Data System (ADS)

Li, Jing; Guo, Tiantian; Gao, Shuai; Jiang, Lin; Zhao, Zhijun; Wang, Yalin

2018-03-01

Big recycled aggregate self compacting concrete is a new type of recycled concrete, which has the advantages of low hydration heat and green environmental protection, but its bending behavior can be affected by different replacement rate. Therefor, in this paper, the research status of big Recycled aggregate self compacting concrete was systematically introduced, and the effect of different replacement rate of big recycled aggregate on failure mode, crack distribution and bending strength of the beam were studied through the bending behavior test of 4 big recycled aggregate self compacting concrete beams. The results show that: The crack distribution of the beam can be affected by the replacement rate; The failure modes of big recycled aggregate beams are the same as those of ordinary concrete; The plane section assumption is applicable to the big recycled aggregate self compacting concrete beam; The higher the replacement rate, the lower the bending strength of big recycled aggregate self compacting concrete beams.

Are Current Atomistic Force Fields Accurate Enough to Study Proteins in Crowded Environments?

PubMed Central

Petrov, Drazen; Zagrovic, Bojan

2014-01-01

The high concentration of macromolecules in the crowded cellular interior influences different thermodynamic and kinetic properties of proteins, including their structural stabilities, intermolecular binding affinities and enzymatic rates. Moreover, various structural biology methods, such as NMR or different spectroscopies, typically involve samples with relatively high protein concentration. Due to large sampling requirements, however, the accuracy of classical molecular dynamics (MD) simulations in capturing protein behavior at high concentration still remains largely untested. Here, we use explicit-solvent MD simulations and a total of 6.4 µs of simulated time to study wild-type (folded) and oxidatively damaged (unfolded) forms of villin headpiece at 6 mM and 9.2 mM protein concentration. We first perform an exhaustive set of simulations with multiple protein molecules in the simulation box using GROMOS 45a3 and 54a7 force fields together with different types of electrostatics treatment and solution ionic strengths. Surprisingly, the two villin headpiece variants exhibit similar aggregation behavior, despite the fact that their estimated aggregation propensities markedly differ. Importantly, regardless of the simulation protocol applied, wild-type villin headpiece consistently aggregates even under conditions at which it is experimentally known to be soluble. We demonstrate that aggregation is accompanied by a large decrease in the total potential energy, with not only hydrophobic, but also polar residues and backbone contributing substantially. The same effect is directly observed for two other major atomistic force fields (AMBER99SB-ILDN and CHARMM22-CMAP) as well as indirectly shown for additional two (AMBER94, OPLS-AAL), and is possibly due to a general overestimation of the potential energy of protein-protein interactions at the expense of water-water and water-protein interactions. Overall, our results suggest that current MD force fields may distort the picture of protein behavior in biologically relevant crowded environments. PMID:24854339

The role of brain extracellular proteins in neuroplasticity and learning.

PubMed

Shashoua, V E

1985-06-01

Double labeling studies of the pattern of protein synthesis in goldfish and mouse brain identified a class of glycoproteins (the ependymins) whose turnover rate was enhanced after training. A variety of control experiments indicated that these macromolecules have an important role in the molecular and cell biology of learning. Antisera to the ependymins when injected into the brains of trained goldfish cause amnesia of a newly acquired behavior. Isolation and localization studies by immunocytochemical methods indicate that the ependymins are released into the brain extracellular fluid by a class of neurosecretory cells. In mammalian brain ependymin-containing cells are highly concentrated in the limibic system. The ependymins are constituted from two disulfide-linked acidic polypeptide chains (M.W.37K and 31K). They contain at least 5% covalently bound carbohydrate per chain with mannose, galactose, N-acetylglucosamine and N-acetylneuraminic acid as the predominant components. The highly soluble ependymins can rapidly polymerize to form an insoluble fibrous matrix if calcium is removed from solution by the addition of a Ca2+-chelating agent or dialysis. The self-aggregation property of the ependymins can be triggered by the depletion of Ca2+ from the extracellular space. Studies of the kinetics of the aggregation phenomenon by measurements of turbidity changes indicate that the process can be terminated but not reversed by restoring Ca2+ to its normal CSF level. Immunohistochemical studies of the brains of trained goldfish show the presence of punctate statining sites in the perimeter of certain cells located in specific brain regions. This suggests that ependymin aggregation might occur in vivo during learning. A molecular hypothesis relating the aggregation properties of the ependymins to neuroplasticity and learning is proposed.

Stabilizing Off-pathway Oligomers by Polyphenol Nanoassemblies for IAPP Aggregation Inhibition

NASA Astrophysics Data System (ADS)

Nedumpully-Govindan, Praveen; Kakinen, Aleksandr; Pilkington, Emily H.; Davis, Thomas P.; Chun Ke, Pu; Ding, Feng

2016-01-01

Experimental studies have shown that many naturally occurring polyphenols have inhibitory effect on the aggregation of several proteins. Here, we use discrete molecular dynamics (DMD) simulations and high-throughput dynamic light scattering (DLS) experiments to study the anti-aggregation effects of two polyphenols, curcumin and resveratrol, on the aggregation of islet amyloid polypeptide (IAPP or amylin). Our DMD simulations suggest that the aggregation inhibition is caused by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols. Our analysis indicates that IAPP-polyphenol hydrogen bonds and π-π stacking combined with hydrophobic interactions are responsible for the stabilization of oligomers. The presence of small oligomers is confirmed with DLS measurements in which nanometer-sized oligomers are found to be stable for up to 7.5 hours, the time frame within which IAPP aggregates in the absence of polyphenols. Our study offers a general anti-aggregation mechanism for polyphenols, and further provides a computational framework for the future design of anti-amyloid aggregation therapeutics.

Distinct Spacing Between Anionic Groups: An Essential Chemical Determinant for Achieving Thiophene-Based Ligands to Distinguish β-Amyloid or Tau Polymorphic Aggregates

PubMed Central

Klingstedt, Therése; Shirani, Hamid; Mahler, Jasmin; Wegenast-Braun, Bettina M; Nyström, Sofie; Goedert, Michel; Jucker, Mathias; Nilsson, K Peter R

2015-01-01

The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the existence of distinct aggregated morphotypes has been suggested to explain the heterogeneous phenotype reported for these diseases. Thus, the development of molecular probes able to distinguish such morphotypes is essential. We report an anionic tetrameric oligothiophene compound that can be utilized for spectral assignment of different morphotypes of β-amyloid or tau aggregates present in transgenic mice at distinct ages. The ability of the ligand to spectrally distinguish between the aggregated morphotypes was reduced when the spacing between the anionic substituents along the conjugated thiophene backbone was altered, which verified that specific molecular interactions between the ligand and the protein aggregate are necessary to detect aggregate polymorphism. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between different morphotypes of protein aggregates. PMID:26013403

A Blood-Brain Barrier (BBB) Disrupter Is Also a Potent α-Synuclein (α-syn) Aggregation Inhibitor

PubMed Central

Shaltiel-Karyo, Ronit; Frenkel-Pinter, Moran; Rockenstein, Edward; Patrick, Christina; Levy-Sakin, Michal; Schiller, Abigail; Egoz-Matia, Nirit; Masliah, Eliezer; Segal, Daniel; Gazit, Ehud

2013-01-01

The development of disease-modifying therapy for Parkinson disease has been a main drug development challenge, including the need to deliver the therapeutic agents to the brain. Here, we examined the ability of mannitol to interfere with the aggregation process of α-synuclein in vitro and in vivo in addition to its blood-brain barrier-disrupting properties. Using in vitro studies, we demonstrated the effect of mannitol on α-synuclein aggregation. Although low concentration of mannitol inhibited the formation of fibrils, high concentration significantly decreased the formation of tetramers and high molecular weight oligomers and shifted the secondary structure of α-synuclein from α-helical to a different structure, suggesting alternative potential pathways for aggregation. When administered to a Parkinson Drosophila model, mannitol dramatically corrected its behavioral defects and reduced the amount of α-synuclein aggregates in the brains of treated flies. In the mThy1-human α-synuclein transgenic mouse model, a decrease in α-synuclein accumulation was detected in several brain regions following treatment, suggesting that mannitol promotes α-synuclein clearance in the cell bodies. It appears that mannitol has a general neuroprotective effect in the transgenic treated mice, which includes the dopaminergic system. We therefore suggest mannitol as a basis for a dual mechanism therapeutic agent for the treatment of Parkinson disease. PMID:23637226

A blood-brain barrier (BBB) disrupter is also a potent α-synuclein (α-syn) aggregation inhibitor: a novel dual mechanism of mannitol for the treatment of Parkinson disease (PD).

PubMed

Shaltiel-Karyo, Ronit; Frenkel-Pinter, Moran; Rockenstein, Edward; Patrick, Christina; Levy-Sakin, Michal; Schiller, Abigail; Egoz-Matia, Nirit; Masliah, Eliezer; Segal, Daniel; Gazit, Ehud

2013-06-14

The development of disease-modifying therapy for Parkinson disease has been a main drug development challenge, including the need to deliver the therapeutic agents to the brain. Here, we examined the ability of mannitol to interfere with the aggregation process of α-synuclein in vitro and in vivo in addition to its blood-brain barrier-disrupting properties. Using in vitro studies, we demonstrated the effect of mannitol on α-synuclein aggregation. Although low concentration of mannitol inhibited the formation of fibrils, high concentration significantly decreased the formation of tetramers and high molecular weight oligomers and shifted the secondary structure of α-synuclein from α-helical to a different structure, suggesting alternative potential pathways for aggregation. When administered to a Parkinson Drosophila model, mannitol dramatically corrected its behavioral defects and reduced the amount of α-synuclein aggregates in the brains of treated flies. In the mThy1-human α-synuclein transgenic mouse model, a decrease in α-synuclein accumulation was detected in several brain regions following treatment, suggesting that mannitol promotes α-synuclein clearance in the cell bodies. It appears that mannitol has a general neuroprotective effect in the transgenic treated mice, which includes the dopaminergic system. We therefore suggest mannitol as a basis for a dual mechanism therapeutic agent for the treatment of Parkinson disease.

Structure, electronic properties, and aggregation behavior of hydroxylated carbon nanotubes

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Oyama, A. B.; Silva-Molina, R. A.; Ruíz-García, J.

2014-11-07

We present a combined experimental and theoretical study to analyze the structure, electronic properties, and aggregation behavior of hydroxylated multiwalled carbon nanotubes (OH–MWCNT). Our MWCNTs have average diameters of ∼2 nm, lengths of approximately 100–300 nm, and a hydroxyl surface coverage θ∼0.1. When deposited on the air/water interface the OH–MWCNTs are partially soluble and the floating units interact and link with each other forming extended foam-like carbon networks. Surface pressure-area isotherms of the nanotube films are performed using the Langmuir balance method at different equilibration times. The films are transferred into a mica substrate and atomic force microscopy images showmore » that the foam like structure is preserved and reveals fine details of their microstructure. Density functional theory calculations performed on model hydroxylated carbon nanotubes show that low energy atomic configurations are found when the OH groups form molecular islands on the nanotube's surface. This patchy behavior for the OH species is expected to produce nanotubes having reduced wettabilities, in line with experimental observations. OH doping yields nanotubes having small HOMO–LUMO energy gaps and generates a nanotube → OH direction for the charge transfer leading to the existence of more hole carriers in the structures. Our synthesized OH–MWCNTs might have promising applications.« less

Structure, electronic properties, and aggregation behavior of hydroxylated carbon nanotubes.

PubMed

López-Oyama, A B; Silva-Molina, R A; Ruíz-García, J; Gámez-Corrales, R; Guirado-López, R A

2014-11-07

We present a combined experimental and theoretical study to analyze the structure, electronic properties, and aggregation behavior of hydroxylated multiwalled carbon nanotubes (OH-MWCNT). Our MWCNTs have average diameters of ~2 nm, lengths of approximately 100-300 nm, and a hydroxyl surface coverage θ~0.1. When deposited on the air/water interface the OH-MWCNTs are partially soluble and the floating units interact and link with each other forming extended foam-like carbon networks. Surface pressure-area isotherms of the nanotube films are performed using the Langmuir balance method at different equilibration times. The films are transferred into a mica substrate and atomic force microscopy images show that the foam like structure is preserved and reveals fine details of their microstructure. Density functional theory calculations performed on model hydroxylated carbon nanotubes show that low energy atomic configurations are found when the OH groups form molecular islands on the nanotube's surface. This patchy behavior for the OH species is expected to produce nanotubes having reduced wettabilities, in line with experimental observations. OH doping yields nanotubes having small HOMO-LUMO energy gaps and generates a nanotube → OH direction for the charge transfer leading to the existence of more hole carriers in the structures. Our synthesized OH-MWCNTs might have promising applications.

Hydrodynamic size-based separation and characterization of protein aggregates from total cell lysates

PubMed Central

Tanase, Maya; Zolla, Valerio; Clement, Cristina C; Borghi, Francesco; Urbanska, Aleksandra M; Rodriguez-Navarro, Jose Antonio; Roda, Barbara; Zattoni, Andrea; Reschiglian, Pierluigi; Cuervo, Ana Maria; Santambrogio, Laura

2016-01-01

Herein we describe a protocol that uses hollow-fiber flow field-flow fractionation (FFF) coupled with multiangle light scattering (MALS) for hydrodynamic size-based separation and characterization of complex protein aggregates. The fractionation method, which requires 1.5 h to run, was successfully modified from the analysis of protein aggregates, as found in simple protein mixtures, to complex aggregates, as found in total cell lysates. In contrast to other related methods (filter assay, analytical ultracentrifugation, gel electrophoresis and size-exclusion chromatography), hollow-fiber flow FFF coupled with MALS allows a flow-based fractionation of highly purified protein aggregates and simultaneous measurement of their molecular weight, r.m.s. radius and molecular conformation (e.g., round, rod-shaped, compact or relaxed). The polyethersulfone hollow fibers used, which have a 0.8-mm inner diameter, allow separation of as little as 20 μg of total cell lysates. In addition, the ability to run the samples in different denaturing and nondenaturing buffer allows defining true aggregates from artifacts, which can form during sample preparation. The protocol was set up using Paraquat-induced carbonylation, a model that induces protein aggregation in cultured cells. This technique will advance the biochemical, proteomic and biophysical characterization of molecular-weight aggregates associated with protein mutations, as found in many CNS degenerative diseases, or chronic oxidative stress, as found in aging, and chronic metabolic and inflammatory conditions. PMID:25521790

Viral Aggregation: Impact on Virus Behavior in the Environment.

PubMed

Gerba, Charles P; Betancourt, Walter Q

2017-07-05

Aggregates of viruses can have a significant impact on quantification and behavior of viruses in the environment. Viral aggregates may be formed in numerous ways. Viruses may form crystal like structures and aggregates in the host cell during replication or may form due to changes in environmental conditions after virus particles are released from the host cells. Aggregates tend to form near the isoelectric point of the virus, under the influence of certain salts and salt concentrations in solution, cationic polymers, and suspended organic matter. The given conditions under which aggregates form in the environment are highly dependent on the type of virus, type of salts in solution (cation, anion. monovalent, divalent) and pH. However, virus type greatly influences the conditions when aggregation/disaggregation will occur, making predictions difficult under any given set of water quality conditions. Most studies have shown that viral aggregates increase the survival of viruses in the environment and resistance to disinfectants, especially with more reactive disinfectants. The presence of viral aggregates may also result in overestimation of removal by filtration processes. Virus aggregation-disaggregation is a complex process and predicting the behavior of any individual virus is difficult under a given set of environmental circumstances without actual experimental data.

Characterizing the mechanical behavior of the zebrafish germ layers

NASA Astrophysics Data System (ADS)

Kealhofer, David; Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Lucio, Adam; Campàs, Otger

Organ morphogenesis and the development of the animal body plan involve complex spatial and temporal control of tissue- and cell-level mechanics. A prime example is the generation of stresses by individual cells to reorganize the tissue. These processes have remained poorly understood due to a lack of techniques to characterize the local constitutive law of the material, which relates local cellular forces to the resulting tissue flows. We have developed a method for quantitative, local in vivo study of material properties in living tissue using magnetic droplet probes. We use this technique to study the material properties of the different zebrafish germ layers using aggregates of zebrafish mesendodermal and ectodermal cells as a model system. These aggregates are ideal for controlled studies of the mechanics of individual germ layers because of the homogeneity of the cell type and the simple spherical geometry. Furthermore, the numerous molecular tools and transgenic lines already developed for this model organism can be applied to these aggregates, allowing us to characterize the contributions of cell cortex tension and cell adhesion to the mechanical properties of the zebrafish germ layers.

Staphylococcal Bap Proteins Build Amyloid Scaffold Biofilm Matrices in Response to Environmental Signals

PubMed Central

Taglialegna, Agustina; Navarro, Susanna; Ventura, Salvador; Garnett, James A.; Matthews, Steve; Penades, José R.; Lasa, Iñigo; Valle, Jaione

2016-01-01

Biofilms are communities of bacteria that grow encased in an extracellular matrix that often contains proteins. The spatial organization and the molecular interactions between matrix scaffold proteins remain in most cases largely unknown. Here, we report that Bap protein of Staphylococcus aureus self-assembles into functional amyloid aggregates to build the biofilm matrix in response to environmental conditions. Specifically, Bap is processed and fragments containing at least the N-terminus of the protein become aggregation-prone and self-assemble into amyloid-like structures under acidic pHs and low concentrations of calcium. The molten globule-like state of Bap fragments is stabilized upon binding of the cation, hindering its self-assembly into amyloid fibers. These findings define a dual function for Bap, first as a sensor and then as a scaffold protein to promote biofilm development under specific environmental conditions. Since the pH-driven multicellular behavior mediated by Bap occurs in coagulase-negative staphylococci and many other bacteria exploit Bap-like proteins to build a biofilm matrix, the mechanism of amyloid-like aggregation described here may be widespread among pathogenic bacteria. PMID:27327765

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development

PubMed Central

Tomar, Dheeraj S.; Kumar, Sandeep; Singh, Satish K.; Goswami, Sumit; Li, Li

2016-01-01

ABSTRACT Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored. PMID:26736022

Investigating the effects of polymer molecular weight and non-solvent content on the phase separation, surface morphology and hydrophobicity of polyvinyl chloride films

NASA Astrophysics Data System (ADS)

Khoryani, Zahra; Seyfi, Javad; Nekoei, Mehdi

2018-01-01

The main aim of this research is to study the effects of polymer molecular weight as well as non-solvent concentration on the phase separation, surface morphology and wettability of polyvinyl chloride (PVC) films. Gel permeation chromatography (GPC) results showed that the Mn of the used PVC grades is 6 × 104, 8.7 × 104 and 1.26 × 105 g/mol. It was found that a proper combination of polymer molecular weight and non-solvent content could result in superhydrophobic and self-cleaning behaviors. Scanning electron microscopy (SEM) results demonstrated that addition of ethanol causes the polymer chains to be severely aggregated at the films' surface forming strand-like structures decorated by nano-scale polymer spheres. The polymer molecular weight was found to affect the degree of porosity which is highly influential on the hydrophobicity of the films. The mechanism of phase separation process was also discussed and it was found that the instantaneous demixing is the dominant mechanism once higher contents of non-solvent were used. However, a delayed demixing mechanism was detected when the lower molecular weight PVC has been used which resulted in a pore-less and dense skin layer. Differential scanning calorimetry was also utilized to study the crystallization and glass transition behavior of samples.

Aggregations of masked shrews (Sorex cinereus): density related mating behavior?

Treesearch

Thomas J. Maier; Katherine L. Doyle

2006-01-01

Large aggregations of shrews have been reported and various explanations offered for this seemingly rare behavior; however, there has been little evidence to support any particular interpretation. We observed two small aggregations of highly active vocalizing Sorex cinereus while performing wildlife surveys in forested habitats in central...

Oxidized quercetin inhibits α-synuclein fibrillization.

PubMed

Zhu, Min; Han, Shubo; Fink, Anthony L

2013-04-01

α-Synucein is a small (14 kDa), abundant, intrinsically disordered presynaptic protein, whose aggregation is believed to be a critical step in Parkinson's disease (PD). Oxidative stress is reported to be a risk factor for dopamine cell degeneration in PD. Flavonoids are suggested to be important antioxidant against oxidative stress. Flavonoids were reported to inhibit fibrillization and disaggregate the preformed fibrils of α-synucein, but the molecular mechanism was still not clear. Quercetin, a well-recognized flavonoid antioxidant, was tested for its inhibition of α-synucein aggregation by thioflavin T assay, light scattering measurement, size-exclusion high performance liquid chromatography, atomic force microscopy, etc. The pre-incubated quercetin exhibited a noticeably stronger inhibition behavior to the fibril formation than that of the freshly prepared. The inhibition is significant in the presence of ortho- and para-benzenediol isomers and inconsiderable in the presence of meta-isomer. The oxidized quercetin species (i.e., chalcantrione, benzyfuranone, quercetinchinone, and other derivatives) cause stronger inhibition than quercetin does because of the elevated polarity and hydrophilicity. Presence of quercetin disaggregates α-synucein fibrils, rather than oligomers and amorphous aggregations. Instead of the antioxidant activity, the 1:1 covalent binding of quercetin with α-synucein, and the increased hydophilicity of the covalently modified α-synucein oligomers or monomers, account for the inhibition of α-synucein fibrillation. Clarification of the molecular mechanism of the inhibition and disaggregation may help to screen safer and more effective flavonoid therapeutic in combating PD. Copyright © 2012. Published by Elsevier B.V.

Real-time monitoring of quorum sensing in 3D-printed bacterial aggregates using scanning electrochemical microscopy.

PubMed

Connell, Jodi L; Kim, Jiyeon; Shear, Jason B; Bard, Allen J; Whiteley, Marvin

2014-12-23

Microbes frequently live in nature as small, densely packed aggregates containing ∼10(1)-10(5) cells. These aggregates not only display distinct phenotypes, including resistance to antibiotics, but also, serve as building blocks for larger biofilm communities. Aggregates within these larger communities display nonrandom spatial organization, and recent evidence indicates that this spatial organization is critical for fitness. Studying single aggregates as well as spatially organized aggregates remains challenging because of the technical difficulties associated with manipulating small populations. Micro-3D printing is a lithographic technique capable of creating aggregates in situ by printing protein-based walls around individual cells or small populations. This 3D-printing strategy can organize bacteria in complex arrangements to investigate how spatial and environmental parameters influence social behaviors. Here, we combined micro-3D printing and scanning electrochemical microscopy (SECM) to probe quorum sensing (QS)-mediated communication in the bacterium Pseudomonas aeruginosa. Our results reveal that QS-dependent behaviors are observed within aggregates as small as 500 cells; however, aggregates larger than 2,000 bacteria are required to stimulate QS in neighboring aggregates positioned 8 μm away. These studies provide a powerful system to analyze the impact of spatial organization and aggregate size on microbial behaviors.

A possible molecular mechanism for the pressure reversal of general anaesthetics: Aggregation of halothane in POPC bilayers at high pressure

NASA Astrophysics Data System (ADS)

Tu, K. M.; Matubayasi, N.; Liang, K. K.; Todorov, I. T.; Chan, S. L.; Chau, P.-L.

2012-08-01

We placed halothane, a general anaesthetic, inside palmitoyloleoylphosphatidylcholine (POPC) bilayers and performed molecular dynamics simulations at atmospheric and raised pressures. We demonstrated that halothane aggregated inside POPC membranes at 20 MPa but not at 40 MPa. The pressure range of aggregation matches that of pressure reversal in whole animals, and strongly suggests that this could be the mechanism for this effect. Combining these results with previous experimental data, we describe a testable hypothesis of how aggregation of general anaesthetics at high pressure can lead to pressure reversal, the effect whereby these drugs lose the efficacy at high pressure.

Molecular insights into early stage aggregation of di-Fmoc-L-lysine in binary mixture of organic solvent and water

NASA Astrophysics Data System (ADS)

Huda, Md Masrul; Rai, Neeraj

Molecular gels are relatively new class of soft materials, which are formed by the supramolecular aggregation of low molecular weight gelators (LMWGs) in organic solvents and/or water. Hierarchical self-assembly of small gelator molecules lead to three-dimensional complex fibrillar networks, which restricts the flow of solvents and results in viscous solid like materials or gels. These gels have drawn significant attentions for their potential applications for drug delivery, tissue engineering, materials for sensors etc. As of now, self-assembly of gelator molecules into one-dimensional fibers is not well understood, although that is very important to design new gelators for desired applications. Here, we present molecular dynamics study that provides molecular level insight into early stage aggregation of selected gelator, di-Fmoc-L-lysine in binary mixture of organic solvent and water. We will present the role of different functional groups of gelator molecule such as aromatic ring, amide, and carboxylic group on aggregation. We will also present the effect of concentrations of gelator and solvent on self-assembly of gelators. This study has captured helical fiber growth and branching of fiber, which is in good agreement with experimental observations.

Interaction between holo transferrin and HSA-PPIX complex in the presence of lomefloxacin: An evaluation of PPIX aggregation in protein-protein interactions

NASA Astrophysics Data System (ADS)

Sattar, Zohreh; Iranfar, Hediye; Asoodeh, Ahmad; Saberi, Mohammad Reza; Mazhari, Mahboobeh; Chamani, Jamshidkhan

2012-11-01

Human serum albumin (HSA) and holo transferrin (TF) are two serum carrier proteins that are able to interact with each other, thereby altering their binding behavior toward their ligands. During the course of this study, the interaction between HSA-PPIX and TF, in the presence and absence of lomefloxacin (LMF), was for the first time investigated using different spectroscopic and molecular modeling techniques. Fluorescence spectroscopy experiments were performed in order to study conformational changes of proteins. The RLS technique was utilized to investigate the effect of LMF on J-aggregation of PPIX, which is the first report of its kind. Our findings present clear-cut evidence for the alteration of interactions between HSA and TF in the presence of PPIX and changes in drug-binding to HSA and HSA-PPIX complex upon interaction with TF. Moreover, molecular modeling studies suggested that the binding site for LMF became switched in the presence of PPIX, and that LMF bound to the site IIA of HSA. The obtained results should give new insight into research in this field and may cast some light on the dynamics of drugs in biological systems.

Ligand-Receptor Interaction Modulates the Energy Landscape of Enzyme-Instructed Self-Assembly of Small Molecules.

PubMed

Haburcak, Richard; Shi, Junfeng; Du, Xuewen; Yuan, Dan; Xu, Bing

2016-11-30

The concurrence of enzymatic reaction and ligand-receptor interactions is common for proteins, but rare for small molecules and has yet to be explored. Here we show that ligand-receptor interaction modulates the morphology of molecular assemblies formed by enzyme-instructed assembly of small molecules. While the absence of ligand-receptor interaction allows enzymatic dephosphorylation of a precursor to generate the hydrogelator that self-assembles to form long nanofibers, the presence of the ligand-receptor interaction biases the pathway to form precipitous aggregates containing short nanofibers. While the hydrogelators self-assemble to form nanofibers or nanoribbons that are unable to bind with the ligand (i.e., vancomycin), the addition of surfactant breaks up the assemblies to restore the ligand-receptor interaction. In addition, an excess amount of the ligands can disrupt the nanofibers and result in the precipitates. As the first example of the use of ligand-receptor interaction to modulate the kinetics of enzymatic self-assembly, this work not only provides a solution to evaluate the interaction between aggregates and target molecules but also offers new insight for understanding the emergent behavior of sophisticated molecular systems having multiple and parallel processes.

Coarse grained study of pluronic F127: Comparison with shorter co-polymers in its interaction with lipid bilayers and self-aggregation in water

NASA Astrophysics Data System (ADS)

Wood, I.; Martini, M. F.; Albano, J. M. R.; Cuestas, M. L.; Mathet, V. L.; Pickholz, M.

2016-04-01

The aim of this work is to understand the interactions of the poloxamer Pluronic F127, with lipid bilayers and its ability to self-associate in an aqueous environment. Molecular dynamics simulations at the coarse-grain scale were performed to address the behavior of single Pluronic F127 and shorter poloxamers unimers in palmitoyl-oleoyl-phosphatidyl-choline model membranes. According to the initial conditions and the poly-ethylene oxide/poly-propylene oxide composition, in water phase the unimer chain collapses into a coil conformation or adopts an interphacial U-shaped - or membrane spanning - distribution. A combination of poly-propylene oxide length, and the poly-ethylene oxide ability to cover poly-propylene oxide, is determinant for the conformation adopted by the unimer in each phase. Results of the simulations showed molecular evidence of strong interaction between Pluronic F127 and model membranes both in stable U-shaped and span conformations. The knowledge of this interaction could contribute to improve drug permeation. Additionally, we investigated the aggregation of one hundred Pluronic F127 unimers in water forming a micelle-like structure, suitable to be used as drug delivery system models.

Partner aggression and problem drinking across the lifespan: how much do they decline?

PubMed

O'Leary, K Daniel; Woodin, Erica M

2005-11-01

Cross-sectional analyses from nationally-representative samples demonstrate significant age-related trends in partner aggression and problem drinking. Both behaviors are most prevalent in the early to mid-twenties and increasingly less common thereafter. Aggregate associations based on percentage of individuals displaying the behavior in each age range are dramatically stronger than those found when correlating individuals' ages and behavior. Multilevel modeling demonstrates that group-level effects do not mask associations found at the level of the individual for either problem drinking or partner aggression. An analysis of recent abstracts from psychology journals showed that issues of aggregate and individual data are rarely if ever discussed, and even well-known statistics books in psychology rarely discuss such issues. The interpretation of aggregate data will become increasing important as psychologists themselves, and in collaboration with epidemiologists and sociologists, have access to large data sets that allow for data aggregation. Both aggregate and individual analyses are valid, although they provide answers to different questions. Individual analyses are necessary for predicting individual behavior; aggregate analyses are useful in policy planning for large scale prevention and intervention. Strengths and limitations of cross-sectional community samples and aggregate data are also discussed.

Ensemble and single particle fluorimetric techniques in concerted action to study the diffusion and aggregation of the glycine receptor α3 isoforms in the cell plasma membrane.

PubMed

Notelaers, Kristof; Smisdom, Nick; Rocha, Susana; Janssen, Daniel; Meier, Jochen C; Rigo, Jean-Michel; Hofkens, Johan; Ameloot, Marcel

2012-12-01

The spatio-temporal membrane behavior of glycine receptors (GlyRs) is known to be of influence on receptor homeostasis and functionality. In this work, an elaborate fluorimetric strategy was applied to study the GlyR α3K and L isoforms. Previously established differential clustering, desensitization and synaptic localization of these isoforms imply that membrane behavior is crucial in determining GlyR α3 physiology. Therefore diffusion and aggregation of homomeric α3 isoform-containing GlyRs were studied in HEK 293 cells. A unique combination of multiple diffraction-limited ensemble average methods and subdiffraction single particle techniques was used in order to achieve an integrated view of receptor properties. Static measurements of aggregation were performed with image correlation spectroscopy (ICS) and, single particle based, direct stochastic optical reconstruction microscopy (dSTORM). Receptor diffusion was measured by means of raster image correlation spectroscopy (RICS), temporal image correlation spectroscopy (TICS), fluorescence recovery after photobleaching (FRAP) and single particle tracking (SPT). The results show a significant difference in diffusion coefficient and cluster size between the isoforms. This reveals a positive correlation between desensitization and diffusion and disproves the notion that receptor aggregation is a universal mechanism for accelerated desensitization. The difference in diffusion coefficient between the clustering GlyR α3L and the non-clustering GlyR α3K cannot be explained by normal diffusion. SPT measurements indicate that the α3L receptors undergo transient trapping and directed motion, while the GlyR α3K displays mild hindered diffusion. These findings are suggestive of differential molecular interaction of the isoforms after incorporation in the membrane. Copyright © 2012 Elsevier B.V. All rights reserved.

Spacer effect on nanostructures and self-assembly in organogels via some bolaform cholesteryl imide derivatives with different spacers

PubMed Central

2013-01-01

In this paper, new bolaform cholesteryl imide derivatives with different spacers were designed and synthesized. Their gelation behaviors in 23 solvents were investigated, and some of them were found to be low molecular mass organic gelators. The experimental results indicated that these as-formed organogels can be regulated by changing the flexible/rigid segments in spacers and organic solvents. Suitable combination of flexible/rigid segments in molecular spacers in the present cholesteryl gelators is favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle and belt to fiber with the change of spacers and solvents. Spectral studies indicated that there existed different H-bond formations between imide groups and assembly modes, depending on the substituent spacers in molecular skeletons. The present work may give some insight into the design and character of new organogelators and soft materials with special molecular structures. PMID:24083361

Spacer effect on nanostructures and self-assembly in organogels via some bolaform cholesteryl imide derivatives with different spacers

NASA Astrophysics Data System (ADS)

Jiao, Tifeng; Gao, Fengqing; Zhang, Qingrui; Zhou, Jingxin; Gao, Faming

2013-10-01

In this paper, new bolaform cholesteryl imide derivatives with different spacers were designed and synthesized. Their gelation behaviors in 23 solvents were investigated, and some of them were found to be low molecular mass organic gelators. The experimental results indicated that these as-formed organogels can be regulated by changing the flexible/rigid segments in spacers and organic solvents. Suitable combination of flexible/rigid segments in molecular spacers in the present cholesteryl gelators is favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle and belt to fiber with the change of spacers and solvents. Spectral studies indicated that there existed different H-bond formations between imide groups and assembly modes, depending on the substituent spacers in molecular skeletons. The present work may give some insight into the design and character of new organogelators and soft materials with special molecular structures.

Correlation of the protein structure and gelling properties in dried egg white products.

PubMed

Handa, A; Hayashi, K; Shidara, H; Kuroda, N

2001-08-01

The relationship between protein structure and aggregation, as well as heat-induced gelling properties, of seven dried egg white (DEW) products was investigated. Strong correlations were found between average molecular weight and hydrophobicity plus surface SH groups of DEW-soluble protein aggregate (SPA). This suggests that hydrophobic interactions and disulfide bond formation between protein molecules were involved in the aggregation. The average molecular weight of DEW products with alkaline pHs was relatively higher than those with neutral pHs and the same degree of protein unfolding, probably because of more disulfide bond formation between protein molecules. In addition, strong correlations were found between hydrophobicity, surface SH groups plus average molecular weight of DEW-SPA, and physical properties of the gels from DEW products. These data indicated that controlling the aggregation of DEW proteins in the dry state is crucial to controlling the gelling properties of DEW.

Nanoscale studies link amyloid maturity with polyglutamine diseases onset

NASA Astrophysics Data System (ADS)

Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler, G.

2016-08-01

The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington’s disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.

Chiroptical studies on supramolecular chirality of molecular aggregates.

PubMed

Sato, Hisako; Yajima, Tomoko; Yamagishi, Akihiko

2015-10-01

The attempts of applying chiroptical spectroscopy to supramolecular chirality are reviewed with a focus on vibrational circular dichroism (VCD). Examples were taken from gels, solids, and monolayers formed by low-molecular mass weight chiral gelators. Particular attention was paid to a group of gelators with perfluoroalkyl chains. The effects of the helical conformation of the perfluoroalkyl chains on the formation of chiral architectures are reported. It is described how the conformation of a chiral gelator was determined by comparing the experimental and theoretical VCD spectra together with a model proposed for the molecular aggregation in fibrils. The results demonstrate the potential utility of the chiroptical method in analyzing organized chiral aggregates. © 2015 Wiley Periodicals, Inc.

Loss of intramolecular electrostatic interactions and limited conformational ensemble may promote self-association of cis-tau peptide.

PubMed

Barman, Arghya; Hamelberg, Donald

2015-03-01

Self-association of proteins can be triggered by a change in the distribution of the conformational ensemble. Posttranslational modification, such as phosphorylation, can induce a shift in the ensemble of conformations. In the brain of Alzheimer's disease patients, the formation of intra-cellular neurofibrillary tangles deposition is a result of self-aggregation of hyper-phosphorylated tau protein. Biochemical and NMR studies suggest that the cis peptidyl prolyl conformation of a phosphorylated threonine-proline motif in the tau protein renders tau more prone to aggregation than the trans isomer. However, little is known about the role of peptidyl prolyl cis/trans isomerization in tau aggregation. Here, we show that intra-molecular electrostatic interactions are better formed in the trans isomer. We explore the conformational landscape of the tau segment containing the phosphorylated-Thr(231)-Pro(232) motif using accelerated molecular dynamics and show that intra-molecular electrostatic interactions are coupled to the isomeric state of the peptidyl prolyl bond. Our results suggest that the loss of intra-molecular interactions and the more restricted conformational ensemble of the cis isomer could favor self-aggregation. The results are consistent with experiments, providing valuable complementary atomistic insights and a hypothetical model for isomer specific aggregation of the tau protein. © 2014 Wiley Periodicals, Inc.

Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species.

PubMed

Zheng, Songyan; Qiu, Difei; Adams, Monica; Li, Jinjiang; Mantri, Rao V; Gandhi, Rajesh

2017-01-01

This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22 *, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.

INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Aggregation Behaviors of a Two-Species System with Lose-Lose Interactions

NASA Astrophysics Data System (ADS)

Song, Mei-Xia; Lin, Zhen-Quan; Li, Xiao-Dong; Ke, Jian-Hong

2010-06-01

We propose an aggregation evolution model of two-species (A- and B-species) aggregates to study the prevalent aggregation phenomena in social and economic systems. In this model, A- and B-species aggregates perform self-exchange-driven growths with the exchange rate kernels K (k,l) = Kkl and L(k,l) = Lkl, respectively, and the two species aggregates perform self-birth processes with the rate kernels J1(k) = J1k and J2(k) = J2k, and meanwhile the interaction between the aggregates of different species A and B causes a lose-lose scheme with the rate kernel H(k,l) = Hkl. Based on the mean-field theory, we investigated the evolution behaviors of the two species aggregates to study the competitions among above three aggregate evolution schemes on the distinct initial monomer concentrations A0 and B0 of the two species. The results show that the evolution behaviors of A- and B-species are crucially dominated by the competition between the two self-birth processes, and the initial monomer concentrations A0 and B0 play important roles, while the lose-lose scheme play important roles in some special cases.

Self-organized, near-critical behavior during aggregation in Dictyostelium discoideum

NASA Astrophysics Data System (ADS)

de Palo, Giovanna; Yi, Darvin; Gregor, Thomas; Endres, Robert

During starvation, the social amoeba Dictyostelium discoideum aggregates artfully via pattern formation into a multicellular slug and finally spores. The aggregation process is mediated by the secretion and sensing of cyclic adenosine monophosphate, leading to the synchronized movement of cells. The whole process is a remarkable example of collective behavior, spontaneously emerging from single-cell chemotaxis. Despite this phenomenon being broadly studied, a precise characterization of the transition from single cells to multicellularity has been elusive. Here, using fluorescence imaging data of thousands of cells, we investigate the role of cell shape in aggregation, demonstrating remarkable transitions in cell behavior. To better understand their functional role, we analyze cell-cell correlations and provide evidence for self-organization at the onset of aggregation (as opposed to leader cells), with features of criticality in this finite system. To capture the mechanism of self-organization, we extend a detailed single-cell model of D.discoideum chemotaxis by adding cell-cell communication. We then use these results to extract a minimal set of rules leading to aggregation in the population model. If universal, similar rules may explain other types of collective cell behavior.

Mechanochromic Luminescence of Aggregation-Induced Emission Luminogens.

PubMed

Dong, Yong Qiang; Lam, Jacky W Y; Tang, Ben Zhong

2015-09-03

Mechanochromic (MC) luminogens have found promising applications in mechanosensors, security papers, and optical storage for their change in emission behaviors in response to mechanical stimuli. Examples on MC luminescent materials are rare before the discovery of MC luminescence in aggregation-induced emission (AIE) luminogens. The twisted conformations of AIE luminogens (AIEgens) with appropriate crystallization capability afford loosely packing patterns, which facilitates their phase transformation in the solid state. The amorphous films of AIEgens exhibit enhanced emission intensity upon pressurization due to the increased molecular interactions, whereas crystals of AIEgens exhibit MC luminescence due to their amorphization by mechanical stimuli. AIEgens enrich the type of MC luminogens but those showing high emission contrast and multicolor emission switching and those working in a turn-on emission mode are seldom reported. Disclosure of the design strategy of high performance MC luminogens and exploration of their high-tech applications may be the future research directions for MC luminogens.

Chiral signs of TPPS co-assemblies with chiral gelators: role of molecular and supramolecular chirality.

PubMed

Wang, Qiuling; Zhang, Li; Yang, Dong; Li, Tiesheng; Liu, Minghua

2016-10-13

A dianionic tetrakis(4-sulfonatophenyl)porphyrin (TPPS) self-assembled into J-aggregates when it co-assembled with a chiral cationic amphiphile via supramolecular gelation. The chiral signs of TPPS J aggregates followed the supramolecular chirality of amphiphilic assemblies rather than the molecular chirality of the amphiphile.

Direct Imaging of Exciton Transport in Tubular Porphyrin Aggregates by Ultrafast Microscopy.

PubMed

Wan, Yan; Stradomska, Anna; Knoester, Jasper; Huang, Libai

2017-05-31

Long-range exciton transport is a key challenge in achieving efficient solar energy harvesting in both organic solar cells and photosynthetic systems. Self-assembled molecular aggregates provide the potential for attaining long-range exciton transport through strong intermolecular coupling. However, there currently lacks an experimental tool to directly characterize exciton transport in space and in time to elucidate mechanisms. Here we report a direct visualization of exciton diffusion in tubular molecular aggregates by transient absorption microscopy with ∼200 fs time resolution and ∼50 nm spatial precision. These direct measurements provide exciton diffusion constants of 3-6 cm 2 s -1 for the tubular molecular aggregates, which are 3-5 times higher than a theoretical lower bound obtained by assuming incoherent hopping. These results suggest that coherent effects play a role, despite the fact that exciton states near the band bottom crucial for transport are only weakly delocalized (over <10 molecules). The methods presented here establish a direct approach for unraveling the mechanisms and main parameters underlying exciton transport in large molecular assemblies.

Spontaneously Assembled Nano-aggregates in Clear Green Tea Infusions from Camellia ptilophylla and Camellia sinensis.

PubMed

Lin, Xiaorong; Gao, Xiong; Chen, Zhongzheng; Zhang, Yuanyuan; Luo, Wei; Li, Xiaofei; Li, Bin

2017-05-10

Tea nano-aggregates spontaneously assembled in clear tea infusions are considered as the precursors of tea cream, although their molecular basis remains obscure. Here, we characterized nano-aggregates in green tea infusions from Camellia ptilophylla, a peculiar tea variety with 6.0% of theobromine, and Camellia sinensis as the control for comparative purpose. Numerous negatively charged spherical colloidal particles of 50-100 nm in diameter were primarily found in both green tea infusions. Catechins, proteins, and carbohydrates were confirmed as the dominant components in green tea nano-aggregates. In addition, iron, copper, nickel, proteins, and gallated catechins exhibited higher aggregating affinity than other components, whereas methylxanthines and calcium contributed to the transformation of nano-aggregates into tea cream. Green tea nano-aggregates were partly destroyed by simulated gastrointestinal digestion, and removing theses peculiar particles dramatically attenuated the bioaccessibility of methylxanthines, theanine, and some catechin monomers in green tea infusions. This study enhanced our knowledge of molecular interactions in the formation of green tea cream and provided insight into physicochemical profiles, phytochemical nature, and functional effects of green tea nano-aggregates.

Atomistic Structure of Mineral Nano-aggregates from Simulated Compaction and Dewatering.

PubMed

Ho, Tuan Anh; Greathouse, Jeffery A; Wang, Yifeng; Criscenti, Louise J

2017-11-10

The porosity of clay aggregates is an important property governing chemical reactions and fluid flow in low-permeability geologic formations and clay-based engineered barrier systems. Pore spaces in clays include interlayer and interparticle pores. Under compaction and dewatering, the size and geometry of such pore spaces may vary significantly (sub-nanometer to microns) depending on ambient physical and chemical conditions. Here we report a molecular dynamics simulation method to construct a complex and realistic clay-like nanoparticle aggregate with interparticle pores and grain boundaries. The model structure is then used to investigate the effect of dewatering and water content on micro-porosity of the aggregates. The results suggest that slow dewatering would create more compact aggregates compared to fast dewatering. Furthermore, the amount of water present in the aggregates strongly affects the particle-particle interactions and hence the aggregate structure. Detailed analyses of particle-particle and water-particle interactions provide a molecular-scale view of porosity and texture development of the aggregates. The simulation method developed here may also aid in modeling the synthesis of nanostructured materials through self-assembly of nanoparticles.

Atomistic Structure of Mineral Nano-aggregates from Simulated Compaction and Dewatering

DOE PAGES

Ho, Tuan Anh; Greathouse, Jeffery A.; Wang, Yifeng; ...

2017-11-10

The porosity of clay aggregates is an important property governing chemical reactions and fluid flow in low-permeability geologic formations and clay-based engineered barrier systems. Pore spaces in clays include interlayer and interparticle pores. Under compaction and dewatering, the size and geometry of such pore spaces may vary significantly (sub-nanometer to microns) depending on ambient physical and chemical conditions. Here we report a molecular dynamics simulation method to construct a complex and realistic clay-like nanoparticle aggregate with interparticle pores and grain boundaries. The model structure is then used to investigate the effect of dewatering and water content on micro-porosity of themore » aggregates. The results suggest that slow dewatering would create more compact aggregates compared to fast dewatering. Furthermore, the amount of water present in the aggregates strongly affects the particle-particle interactions and hence the aggregate structure. Detailed analyses of particle-particle and water-particle interactions provide a molecular-scale view of porosity and texture development of the aggregates. The simulation method developed here may also aid in modeling the synthesis of nanostructured materials through self-assembly of nanoparticles.« less

Construction of the Free Energy Landscape of Peptide Aggregation from Molecular Dynamics Simulations.

PubMed

Riccardi, Laura; Nguyen, Phuong H; Stock, Gerhard

2012-04-10

To describe the structure and dynamics of oligomers during peptide aggregation, a method is proposed that considers both the intramolecular and intermolecular structures of the multimolecule system and correctly accounts for its degeneracy. The approach is based on the "by-parts" strategy, which partitions a complex molecular system into parts, determines the metastable conformational states of each part, and describes the overall conformational state of the system in terms of a product basis of the states of the parts. Starting from a molecular dynamics simulation of n molecules, the method consists of three steps: (i) characterization of the intramolecular structure, that is, of the conformational states of a single molecule in the presence of the other molecules (e.g., β-strand or random coil); (ii) characterization of the intermolecular structure through the identification of all occurring aggregate states of the peptides (dimers, trimers, etc.); and (iii) construction of the overall conformational states of the system in terms of a product basis of the n "single-molecule" states and the aggregate states. Considering the Alzheimer β-amyloid peptide fragment Aβ16-22 as a first application, about 700 overall conformational states of the trimer (Aβ16-22)3 were constructed from all-atom molecular dynamics simulation in explicit water. Based on these states, a transition network reflecting the free energy landscape of the aggregation process can be constructed that facilitates the identification of the aggregation pathways.

Cooperative structural transitions in amyloid-like aggregation

NASA Astrophysics Data System (ADS)

Steckmann, Timothy; Bhandari, Yuba R.; Chapagain, Prem P.; Gerstman, Bernard S.

2017-04-01

Amyloid fibril aggregation is associated with several horrific diseases such as Alzheimer's, Creutzfeld-Jacob, diabetes, Parkinson's, and others. Although proteins that undergo aggregation vary widely in their primary structure, they all produce a cross-β motif with the proteins in β-strand conformations perpendicular to the fibril axis. The process of amyloid aggregation involves forming myriad different metastable intermediate aggregates. To better understand the molecular basis of the protein structural transitions and aggregation, we report on molecular dynamics (MD) computational studies on the formation of amyloid protofibrillar structures in the small model protein ccβ, which undergoes many of the structural transitions of the larger, naturally occurring amyloid forming proteins. Two different structural transition processes involving hydrogen bonds are observed for aggregation into fibrils: the breaking of intrachain hydrogen bonds to allow β-hairpin proteins to straighten, and the subsequent formation of interchain H-bonds during aggregation into amyloid fibrils. For our MD simulations, we found that the temperature dependence of these two different structural transition processes results in the existence of a temperature window that the ccβ protein experiences during the process of forming protofibrillar structures. This temperature dependence allows us to investigate the dynamics on a molecular level. We report on the thermodynamics and cooperativity of the transformations. The structural transitions that occurred in a specific temperature window for ccβ in our investigations may also occur in other amyloid forming proteins but with biochemical parameters controlling the dynamics rather than temperature.

Flexural behavior of reinforced concrete beam with polymer coated pumice

NASA Astrophysics Data System (ADS)

Nainggolan, Christin Remayanti; Wijatmiko, Indradi; Wibowo, Ari

2017-09-01

Sustainable development has become an important issue due to the increasing consideration of preserving the nature. Many alternative for coarse aggregate replacement have been investigated ranging from natural and fabricated aggregates. In this study, natural aggregate pumice was investigated since it offers lower density that give paramount benefit in reducing total building weight and hence reducing the earthquake excitation effect and optimizing the structural dimension. However, the characteristic of porous surfaces of pumice causes excessive water absorption during concrete mixing process. Therefore, to reduce the additional water, the pumice aggregates were coated with polymer. The tested specimens consisted of normal concrete beams (NCB), uncoated pumice aggregate concrete beam (UPA) and polymer coated pumice aggregate concrete beam (PCP). The objective of the research was to obtain the effect of coating on the pumice aggregate to the flexural behavior of concrete beams. The lateral load-displacement behavior, ductility and collapse mechanism were studied. The results showed that there were only marginal drop on the load-carrying capacity of the pumice aggregate beam compared to those of normal beam. Additionally, the ductility coefficient of specimens UPA and PCP decreased of 11,97% and 14,03% respectively compared to NCB, and the ultimate load capacity decreased less than 1%. Overall, the pumice aggregate showed good characteristic for replacing normal coarse aggregate.

Engineered metal based nanomaterials in aqueous environments: Interactions, transformations and implications

NASA Astrophysics Data System (ADS)

Mudunkotuwa, Imali Ama

Nanoscience and nanotechnology offer potential routes towards addressing critical issues such as clean and sustainable energy, environmental protection and human health. Specifically, metal and metal oxide nanomaterials are found in a wide range of applications and therefore hold a greater potential of possible release into the environment or for the human to be exposed. Understanding the aqueous phase behavior of metal and metal oxide nanomaterials is a key factor in the safe design of these materials because their interactions with living systems are always mediated through the aqueous phase. Broadly the transformations in the aqueous phase can be classified as dissolution, aggregation and adsorption which are dependent and linked processes to one another. The complexity of these processes at the liquid-solid interface has therefore been one of the grand challenges that has persisted since the beginning of nanotechnology. Although classical models provide guidance for understanding dissolution and aggregation of nanoparticles in water, there are many uncertainties associated with the recent findings. This is often due to a lack of fundamental knowledge of the surface structure and surface energetics for very small particles. Therefore currently the environmental health and safety studies related to nanomaterials are more focused on understanding the surface chemistry that governs the overall processes in the liquid-solid interfacial region at the molecular level. The metal based nanomaterials focused on in this dissertation include TiO2, ZnO, Cu and CuO. These are among the most heavily used in a number of applications ranging from uses in the construction industry to cosmetic formulation. Therefore they are produced in large scale and have been detected in the environment. There is debate within the scientific community related to their safety as a result of the lack of understanding on the surface interactions that arise from the detailed nature of the surfaces. Specifically, the interactions of these metal and metal oxide nanoparticles with environmental and biological ligands in the solutions have demonstrated dramatic alterations in their aqueous phase behavior in terms of dissolution and aggregation. Dissolution and aggregation are among the determining factors of nanoparticle uptake and toxicity. Furthermore, solution conditions such as ionic strength and pH can act as controlling parameters for surface ligand adsorption while adsorbed ligands themselves undergo surface induced structural and conformational changes. Because, nanomaterials in both the environment and in biological systems are subjected to a wide range of matrix conditions they are in fact dynamic and not static entities. Thus monitoring and tracking these nanomaterials in real systems can be extremely challenging which requires a thorough understanding of the surface chemistry governing their transformations. The work presented in this dissertation attempts to bridge the gap between the dynamic processing of these nanomaterials, the details of the molecular level processes that occur at the liquid-solid interfacial region and potential environmental and biological interactions. Extensive nanomaterial characterization is an integral part of these investigations and all the materials presented here are thoroughly analyzed for particle size, shape, surface area, bulk and surface compositions. Detailed spectroscopic analysis was used to acquire molecular information of the processes in the liquid-solid interfacial region and the outcomes are linked with the macroscopic analysis with the aid of dynamic and static light scattering techniques. Furthermore, emphasis is given to the size dependent behavior and theoretical modeling is adapted giving careful consideration to the details of the physicochemical characterization and molecular information unique to the nanomaterials.

Growth properties of protoplanetary dust in a long-term microgravity experiment

NASA Astrophysics Data System (ADS)

Brisset, Julie; Kothe, Stefan; Weidling, Rene; Heisselmann, Daniel; Blum, Juergen

2014-11-01

In the very first steps of the formation of a new planetary system, dust agglomerates and grows inside the protoplanetary disk that rotates around the newly formed star. In this disk, collisions between the dust particles, induced by interactions with the surrounding gas, lead to sticking. Aggregates start growing until their sizes and relative velocities are high enough for collisions to result in bouncing or fragmentation. As part of a series of microgravity experiments aiming at the investigation of the transitions between sticking, bouncing and fragmentation of colliding dust aggregates, the Suborbital Particle and Aggregation Experiment (SPACE) was designed, built and operated both at the drop tower in Bremen (August 2011) and on the REXUS 12 suborbital rocket (March 2012). The SPACE experiment allowed for the observation of collisions between aggregates of sizes of a few 100 µm that were composed of SiO2, a commonly used protoplanetary dust analog material. At velocities below 10 cm/s, clusters composed of a high number of aggregates (more than 10^4) formed and grew to sizes of up to 5 mm. The analysis of these collisions delivered valuable input to a current dust collision model, which maps the outcome of collisions depending on the aggregate sizes and their relative velocities. The sticking probability of sub-mm-sized dust aggregates could directly be measured during the suborbital rocket flight, over a velocity range covering the transition between the sticking and bouncing regimes. In addition, the evolution of clusters formed from sub-mm-sized aggregates during the different experiments could be observed and some of their intrinsic properties derived. The measured characteristics were the cluster fractal dimensions, the tensile strength of their outer aggregate layer and the effective surface energy of their constituents. Threshold energies for cluster restructuring and fragmentation could also be determined. All these cluster properties are important input parameters for molecular dynamics or numerical simulations investigating the behavior of macroscopic clusters (>1 mm in size) in protoplanetary disks.

A rationally designed six-residue swap generates comparability in the aggregation behavior of α-synuclein and β-synuclein.

PubMed

Roodveldt, Cintia; Andersson, August; De Genst, Erwin J; Labrador-Garrido, Adahir; Buell, Alexander K; Dobson, Christopher M; Tartaglia, Gian Gaetano; Vendruscolo, Michele

2012-11-06

The aggregation process of α-synuclein, a protein closely associated with Parkinson's disease, is highly sensitive to sequence variations. It is therefore of great importance to understand the factors that define the aggregation propensity of specific mutational variants as well as their toxic behavior in the cellular environment. In this context, we investigated the extent to which the aggregation behavior of α-synuclein can be altered to resemble that of β-synuclein, an aggregation-resistant homologue of α-synuclein not associated with disease, by swapping residues between the two proteins. Because of the vast number of possible swaps, we have applied a rational design procedure to single out a mutational variant, called α2β, in which two short stretches of the sequence in the NAC region have been replaced in α-synuclein from β-synuclein. We find not only that the aggregation rate of α2β is close to that of β-synuclein, being much lower than that of α-synuclein, but also that α2β effectively changes the cellular toxicity of α-synuclein to a value similar to that of β-synuclein upon exposure of SH-SY5Y cells to preformed oligomers. Remarkably, control experiments on the corresponding mutational variant of β-synuclein, called β2α, confirmed that the mutations that we have identified also shift the aggregation behavior of this protein toward that of α-synuclein. These results demonstrate that it is becoming possible to control in quantitative detail the sequence code that defines the aggregation behavior and toxicity of α-synuclein.

Curcumin Treatment Improves Motor Behavior in α-Synuclein Transgenic Mice

PubMed Central

Spinelli, Kateri J.; Osterberg, Valerie R.; Meshul, Charles K.; Soumyanath, Amala; Unni, Vivek K.

2015-01-01

The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ~5 ng/mL and ~12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease. PMID:26035833

Dimension dependence of clustering dynamics in models of ballistic aggregation and freely cooling granular gas

NASA Astrophysics Data System (ADS)

Paul, Subhajit; Das, Subir K.

2018-03-01

Via event-driven molecular dynamics simulations we study kinetics of clustering in assemblies of inelastic particles in various space dimensions. We consider two models, viz., the ballistic aggregation model (BAM) and the freely cooling granular gas model (GGM), for each of which we quantify the time dependence of kinetic energy and average mass of clusters (that form due to inelastic collisions). These quantities, for both the models, exhibit power-law behavior, at least in the long time limit. For the BAM, corresponding exponents exhibit strong dimension dependence and follow a hyperscaling relation. In addition, in the high packing fraction limit the behavior of these quantities become consistent with a scaling theory that predicts an inverse relation between energy and mass. On the other hand, in the case of the GGM we do not find any evidence for such a picture. In this case, even though the energy decay, irrespective of packing fraction, matches quantitatively with that for the high packing fraction picture of the BAM, it is inversely proportional to the growth of mass only in one dimension, and the growth appears to be rather insensitive to the choice of the dimension, unlike the BAM.

Coarse-Grained Molecular Simulation of the Hierarchical Self-Assembly of π-Conjugated Optoelectronic Peptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mansbach, Rachael A.; Ferguson, Andrew L.

Self-assembled aggregates of peptides containing aromatic groups possess optoelectronic properties that make them attractive targets for the fabrication of biocompatible electronics. Molecular-level understanding of how the microscopic peptide chemistry influences the properties of the aggregates is vital for rational peptide design. We construct a coarse-grained model of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp (DFAG-OPV3-GAFD) peptides containing OPV3 (distyrylbenzene) π-conjugated cores explicitly parameterized against all-atom calculations and perform molecular dynamics simulations of the self-assembly of hundreds of molecules over hundreds of nanoseconds. We observe a hierarchical assembly mechanism wherein ~2-8 peptides assemble into stacks with aligned aromatic cores that subsequently form elliptical aggregates and ultimately amore » branched network with a fractal dimensionality of ~1.5. The assembly dynamics are well described by a Smoluchowski coagulation process for which we extract rate constants from the molecular simulations to both furnish insight into the microscopic assembly kinetics and extrapolate our aggregation predictions to time and length scales beyond the reach of molecular simulation. Lastly, this study presents new molecular-level understanding of the morphology and dynamics of the spontaneous self-assembly of DFAG-OPV3-GAFD peptides and establishes a systematic protocol to develop coarse-grained models of optoelectronic peptides for the exploration and design of π-conjugated peptides with tunable optoelectronic properties.« less

Coarse-Grained Molecular Simulation of the Hierarchical Self-Assembly of π-Conjugated Optoelectronic Peptides

DOE PAGES

Mansbach, Rachael A.; Ferguson, Andrew L.

2017-02-10

Self-assembled aggregates of peptides containing aromatic groups possess optoelectronic properties that make them attractive targets for the fabrication of biocompatible electronics. Molecular-level understanding of how the microscopic peptide chemistry influences the properties of the aggregates is vital for rational peptide design. We construct a coarse-grained model of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp (DFAG-OPV3-GAFD) peptides containing OPV3 (distyrylbenzene) π-conjugated cores explicitly parameterized against all-atom calculations and perform molecular dynamics simulations of the self-assembly of hundreds of molecules over hundreds of nanoseconds. We observe a hierarchical assembly mechanism wherein ~2-8 peptides assemble into stacks with aligned aromatic cores that subsequently form elliptical aggregates and ultimately amore » branched network with a fractal dimensionality of ~1.5. The assembly dynamics are well described by a Smoluchowski coagulation process for which we extract rate constants from the molecular simulations to both furnish insight into the microscopic assembly kinetics and extrapolate our aggregation predictions to time and length scales beyond the reach of molecular simulation. Lastly, this study presents new molecular-level understanding of the morphology and dynamics of the spontaneous self-assembly of DFAG-OPV3-GAFD peptides and establishes a systematic protocol to develop coarse-grained models of optoelectronic peptides for the exploration and design of π-conjugated peptides with tunable optoelectronic properties.« less

Swarming Mechanisms in the Yellow Fever Mosquito: Aggregation Pheromones are Involved in the Mating Behavior of Aedes aegypti

DTIC Science & Technology

2014-12-01

behavior of Aedes aegypti Emadeldin Y. Fawaz1, Sandra A. Allan2, Ulrich R. Bernier2, Peter J. Obenauer3, and Joseph W. Diclaro II1 1Vector Biology... Aedes aegypti swarming behavior and identified associated chemical cues. Novel evidence is provided that Ae. aegypti females aggregate by means of...the isolated aggregation pheromones in controlling Ae. aegypti. Journal of Vector Ecology 39 (2): 347-354. 2014. Keyword Index: Aedes aegypti, swarm

EGCG in Green Tea Induces Aggregation of HMGB1 Protein through Large Conformational Changes with Polarized Charge Redistribution

NASA Astrophysics Data System (ADS)

Meng, Xuan-Yu; Li, Baoyu; Liu, Shengtang; Kang, Hongsuk; Zhao, Lin; Zhou, Ruhong

2016-02-01

As a major effective component in green tea, (-)-epigallocatechin-3-gallate (EGCG)’s potential benefits to human health have been widely investigated. Recent experimental evidences indicate that EGCG can induce the aggregation of HMGB1 protein, a late mediator of inflammation, which subsequently stimulates the autophagic degradation and thus provides protection from lethal endotoxemia and sepsis. In this study, we use molecular dynamics (MD) simulations to explore the underlying molecular mechanism of this aggregation of HMGB1 facilitated by EGCG. Our simulation results reveal that EGCG firmly binds to HMGB1 near Cys106, which supports previous preliminary experimental evidence. A large HMGB1 conformational change is observed, where Box A and Box B, two homogenous domains of HMGB1, are repositioned and packed together by EGCG. This new HMGB1 conformation has large molecular polarity and distinctive electrostatic potential surface. We suggest that the highly polarized charge distribution leads to the aggregation of HMGB1, which differs from the previous hypothesis that two HMGB1 monomers are linked by the dimer of EGCG. Possible aggregating modes have also been investigated with potential of mean force (PMF) calculations. Finally, we conclude that the conformation induced by EGCG is more aggregation-prone with higher binding free energies as compared to those without EGCG.

Surface interaction forces of cellulose nanocrystals grafted with thermoresponsive polymer brushes.

PubMed

Zoppe, Justin O; Osterberg, Monika; Venditti, Richard A; Laine, Janne; Rojas, Orlando J

2011-07-11

The colloidal stability and thermoresponsive behavior of poly(N-isopropylacrylamide) brushes grafted from cellulose nanocrystals (CNCs) of varying graft densities and molecular weights was investigated. Indication of the grafted polymer brushes was obtained after AFM imaging of CNCs adsorbed on silica. Also, aggregation of the nanoparticles carrying grafts of high degree of polymerization was observed. The responsiveness of grafted CNCs in aqueous dispersions and as an ultrathin film was evaluated by using light scattering, viscosimetry, and colloidal probe microscopy (CPM). Light transmittance measurements showed temperature-dependent aggregation originating from the different graft densities and molecular weights. The lower critical solution temperature (LCST) of grafted poly(NiPAAm) brushes was found to decrease with the ionic strength, as is the case for free poly(NiPAAm) in aqueous solution. Thermal responsive behavior of grafted CNCs in aqueous dispersions was observed by a sharp increase in dispersion viscosity as the temperature approached the LCST. CPM in liquid media for asymmetric systems consisting of ultrathin films of CNCs and a colloidal silica probe showed the distinctive effects of the grafted polymer brushes on interaction and adhesive forces. The origin of such forces was found to be mainly electrostatic and steric in the case of bare and grafted CNCs, respectively. A decrease in the onset of attractive and adhesion forces of grafted CNCs films were observed with the ionic strength of the aqueous solution. The decreased mobility of polymer brushes upon partial collapse and decreased availability of hydrogen bonding sites with higher electrolyte concentration were hypothesized as the main reasons for the less prominent polymer bridging between interacting surfaces.

Alzheimer Abeta(1-42) monomer adsorbed on the self-assembled monolayers.

PubMed

Wang, Qiuming; Zhao, Jun; Yu, Xiang; Zhao, Chao; Li, Lingyan; Zheng, Jie

2010-08-03

Amyloid-beta (Abeta) peptide aggregation on the cell membranes is a key pathological event responsible for neuron cell death in Alzheimer's disease (AD). We present a collection of molecular docking and molecular dynamics simulations to study the conformational dynamics and adsorption behavior of Abeta monomer on the self-assembled monolayer (SAM), in comparison to Abeta structure in bulk solution. Two distinct Abeta conformations (i.e., alpha-helix and beta-hairpin) are selected as initial structures to mimic different adsorption states, whereas four SAM surfaces with different end groups in hydrophobicity and charge distribution are used to examine the effect of surface chemistry on Abeta structure and adsorption. Simulation results show that alpha-helical monomer displays higher structural stability than beta-hairpin monomer on all SAMs, suggesting that the preferential conformation of Abeta monomer could be alpha-helical or random structure when bound to surfaces. Structural stability and adsorption behavior of Abeta monomer on the SAMs originates from competitive interactions between Abeta and SAM and between SAM and interfacial water, which involve the conformation of Abeta, the surface chemistry of SAM, and the structure and dynamics of interfacial waters. The relative net binding affinity of Abeta with the SAMs is in the favorable order of COOH-SAM > NH(2)-SAM > CH(3)-SAM > OH-SAM, highlighting the importance of electrostatic and hydrophobic interactions for driving Abeta adsorption at the SAMs, but both interactions contribute differently to each Abeta-SAM complex. This work provides parallel insights into the understanding of Abeta structure and aggregation on cell membrane.

Intrinsically disordered proteins as molecular shields†

PubMed Central

Chakrabortee, Sohini; Tripathi, Rashmi; Watson, Matthew; Kaminski Schierle, Gabriele S.; Kurniawan, Davy P.; Kaminski, Clemens F.; Wise, Michael J.; Tunnacliffe, Alan

2017-01-01

The broad family of LEA proteins are intrinsically disordered proteins (IDPs) with several potential roles in desiccation tolerance, or anhydrobiosis, one of which is to limit desiccation-induced aggregation of cellular proteins. We show here that this activity, termed molecular shield function, is distinct from that of a classical molecular chaperone, such as HSP70 – while HSP70 reduces aggregation of citrate synthase (CS) on heating, two LEA proteins, a nematode group 3 protein, AavLEA1, and a plant group 1 protein, Em, do not; conversely, the LEA proteins reduce CS aggregation on desiccation, while HSP70 lacks this ability. There are also differences in interaction with client proteins – HSP70 can be co-immunoprecipitated with a polyglutamine-containing client, consistent with tight complex formation, whereas the LEA proteins can not, although a loose interaction is observed by Förster resonance energy transfer. In a further exploration of molecular shield function, we demonstrate that synthetic polysaccharides, like LEA proteins, are able to reduce desiccation-induced aggregation of a water-soluble proteome, consistent with a steric interference model of anti-aggregation activity. If molecular shields operate by reducing intermolecular cohesion rates, they should not protect against intramolecular protein damage. This was tested using the monomeric red fluorescent protein, mCherry, which does not undergo aggregation on drying, but the absorbance and emission spectra of its intrinsic fluorophore are dramatically reduced, indicative of intramolecular conformational changes. As expected, these changes are not prevented by AavLEA1, except for a slight protection at high molar ratios, and an AavLEA1-mCherry fusion protein is damaged to the same extent as mCherry alone. A recent hypothesis proposed that proteomes from desiccation-tolerant species contain a higher degree of disorder than intolerant examples, and that this might provide greater intrinsic stability, but a bioinformatics survey does not support this, since there are no significant differences in the degree of disorder between desiccation tolerant and intolerant species. It seems clear therefore that molecular shield function is largely an intermolecular activity implemented by specialist IDPs, distinct from molecular chaperones, but with a role in proteostasis. PMID:21909508

Intrinsically disordered proteins as molecular shields.

PubMed

Chakrabortee, Sohini; Tripathi, Rashmi; Watson, Matthew; Schierle, Gabriele S Kaminski; Kurniawan, Davy P; Kaminski, Clemens F; Wise, Michael J; Tunnacliffe, Alan

2012-01-01

The broad family of LEA proteins are intrinsically disordered proteins (IDPs) with several potential roles in desiccation tolerance, or anhydrobiosis, one of which is to limit desiccation-induced aggregation of cellular proteins. We show here that this activity, termed molecular shield function, is distinct from that of a classical molecular chaperone, such as HSP70 - while HSP70 reduces aggregation of citrate synthase (CS) on heating, two LEA proteins, a nematode group 3 protein, AavLEA1, and a plant group 1 protein, Em, do not; conversely, the LEA proteins reduce CS aggregation on desiccation, while HSP70 lacks this ability. There are also differences in interaction with client proteins - HSP70 can be co-immunoprecipitated with a polyglutamine-containing client, consistent with tight complex formation, whereas the LEA proteins can not, although a loose interaction is observed by Förster resonance energy transfer. In a further exploration of molecular shield function, we demonstrate that synthetic polysaccharides, like LEA proteins, are able to reduce desiccation-induced aggregation of a water-soluble proteome, consistent with a steric interference model of anti-aggregation activity. If molecular shields operate by reducing intermolecular cohesion rates, they should not protect against intramolecular protein damage. This was tested using the monomeric red fluorescent protein, mCherry, which does not undergo aggregation on drying, but the absorbance and emission spectra of its intrinsic fluorophore are dramatically reduced, indicative of intramolecular conformational changes. As expected, these changes are not prevented by AavLEA1, except for a slight protection at high molar ratios, and an AavLEA1-mCherry fusion protein is damaged to the same extent as mCherry alone. A recent hypothesis proposed that proteomes from desiccation-tolerant species contain a higher degree of disorder than intolerant examples, and that this might provide greater intrinsic stability, but a bioinformatics survey does not support this, since there are no significant differences in the degree of disorder between desiccation tolerant and intolerant species. It seems clear therefore that molecular shield function is largely an intermolecular activity implemented by specialist IDPs, distinct from molecular chaperones, but with a role in proteostasis.

Interference between Coulombic and CT-mediated couplings in molecular aggregates: H- to J-aggregate transformation in perylene-based π-stacks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hestand, Nicholas J.; Spano, Frank C.

2015-12-28

The spectroscopic differences between J and H-aggregates are traditionally attributed to the spatial dependence of the Coulombic coupling, as originally proposed by Kasha. However, in tightly packed molecular aggregates wave functions on neighboring molecules overlap, leading to an additional charge transfer (CT) mediated exciton coupling with a vastly different spatial dependence. The latter is governed by the nodal patterns of the molecular LUMOs and HOMOs from which the electron (t{sub e}) and hole (t{sub h}) transfer integrals derive. The sign of the CT-mediated coupling depends on the sign of the product t{sub e}t{sub h} and is therefore highly sensitive tomore » small (sub-Angstrom) transverse displacements or slips. Given that Coulombic and CT-mediated couplings exist simultaneously in tightly packed molecular systems, the interference between the two must be considered when defining J and H-aggregates. Generally, such π-stacked aggregates do not abide by the traditional classification scheme of Kasha: for example, even when the Coulomb coupling is strong the presence of a similarly strong but destructively interfering CT-mediated coupling results in “null-aggregates” which spectroscopically resemble uncoupled molecules. Based on a Frenkel/CT Holstein Hamiltonian that takes into account both sources of electronic coupling as well as intramolecular vibrations, vibronic spectral signatures are developed for integrated Frenkel/CT systems in both the perturbative and resonance regimes. In the perturbative regime, the sign of the lowest exciton band curvature, which rigorously defines J and H-aggregation, is directly tracked by the ratio of the first two vibronic peak intensities. Even in the resonance regime, the vibronic ratio remains a useful tool to evaluate the J or H nature of the system. The theory developed is applied to the reversible H to J-aggregate transformations recently observed in several perylene bisimide systems.« less

Cyclic Behavior of Low Rise Concrete Shear Walls Containing Recycled Coarse and Fine Aggregates.

PubMed

Qiao, Qiyun; Cao, Wanlin; Qian, Zhiwei; Li, Xiangyu; Zhang, Wenwen; Liu, Wenchao

2017-12-07

In this study, the cyclic behaviors of low rise concrete shear walls using recycled coarse or fine aggregates were investigated. Eight low rise Recycled Aggregates Concrete (RAC) shear wall specimens were designed and tested under a cyclic loading. The following parameters were varied: replacement percentages of recycled coarse or fine aggregates, reinforcement ratio, axial force ratio and X-shaped rebars brace. The failure characteristics, hysteretic behavior, strength and deformation capacity, strain characteristics and stiffness were studied. Test results showed that the using of the Recycled Coarse Aggregates (RCA) and its replacement ratio had almost no influence on the mechanical behavior of the shear wall; however, the using of Recycled Fine Aggregates (RFA) had a certain influence on the ductility of the shear wall. When the reinforcement ratio increased, the strength and ductility also increased. By increasing the axial force ratio, the strength increased but the ductility decreased significantly. The encased brace had a significant effect on enhancing the RAC shear walls. The experimental maximum strengths were evaluated with existing design codes, it was indicated that the strength evaluation of the low rise RAC shear walls can follow the existing design codes of the conventional concrete shear walls.

Dynamics of proteins aggregation. I. Universal scaling in unbounded media

NASA Astrophysics Data System (ADS)

Zheng, Size; Javidpour, Leili; Shing, Katherine S.; Sahimi, Muhammad

2016-10-01

It is well understood that in some cases proteins do not fold correctly and, depending on their environment, even properly-folded proteins change their conformation spontaneously, taking on a misfolded state that leads to protein aggregation and formation of large aggregates. An important factor that contributes to the aggregation is the interactions between the misfolded proteins. Depending on the aggregation environment, the aggregates may take on various shapes forming larger structures, such as protein plaques that are often toxic. Their deposition in tissues is a major contributing factor to many neuro-degenerative diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and prion. This paper represents the first part in a series devoted to molecular simulation of protein aggregation. We use the PRIME, a meso-scale model of proteins, together with extensive discontinuous molecular dynamics simulation to study the aggregation process in an unbounded fluid system, as the first step toward MD simulation of the same phenomenon in crowded cellular environments. Various properties of the aggregates have been computed, including dynamic evolution of aggregate-size distribution, mean aggregate size, number of peptides that contribute to the formation of β sheets, number of various types of hydrogen bonds formed in the system, radius of gyration of the aggregates, and the aggregates' diffusivity. We show that many of such quantities follow dynamic scaling, similar to those for aggregation of colloidal clusters. In particular, at long times the mean aggregate size S(t) grows with time as, S(t) ˜ tz, where z is the dynamic exponent. To our knowledge, this is the first time that the qualitative similarity between aggregation of proteins and colloidal aggregates has been pointed out.

Ab initio molecular simulations on specific interactions between amyloid beta and monosaccharides

NASA Astrophysics Data System (ADS)

Nomura, Kazuya; Okamoto, Akisumi; Yano, Atsushi; Higai, Shin'ichi; Kondo, Takashi; Kamba, Seiji; Kurita, Noriyuki

2012-09-01

Aggregation of amyloid β (Aβ) peptides, which is a key pathogenetic event in Alzheimer's disease, can be caused by cell-surface saccharides. We here investigated stable structures of the solvated complexes of Aβ with some types of monosaccharides using molecular simulations based on protein-ligand docking and classical molecular mechanics methods. Moreover, the specific interactions between Aβ and the monosaccharides were elucidated at an electronic level by ab initio fragment molecular orbital calculations. Based on the results, we proposed which type of monosaccharide prefers to have large binding affinity to Aβ and inhibit the Aβ aggregation.

Computational study of aggregation mechanism in human lysozyme[D67H

PubMed Central

Patel, Dharmeshkumar

2017-01-01

Aggregation of proteins is an undesired phenomena that affects both human health and bioengineered products such as therapeutic proteins. Finding preventative measures could be facilitated by a molecular-level understanding of dimer formation, which is the first step in aggregation. Here we present a molecular dynamics (MD) study of dimer formation propensity in human lysozyme and its D67H variant. Because the latter protein aggregates while the former does not, they offer an ideal system for testing the feasibility of the proposed MD approach which comprises three stages: i) partially unfolded conformers involved in dimer formation are generated via high-temperature MD simulations, ii) potential dimer structures are searched using docking and refined with MD, iii) free energy calculations are performed to find the most stable dimer structure. Our results provide a detailed explanation for how a single mutation (D67H) turns human lysozyme from non-aggregating to an aggregating protein. Conversely, the proposed method can be used to identify the residues causing aggregation in a protein, which can be mutated to prevent it. PMID:28467454

Aggregation of montmorillonite and organic matter in aqueous media containing artificial seawater.

PubMed

Furukawa, Yoko; Watkins, Janet L; Kim, Jinwook; Curry, Kenneth J; Bennett, Richard H

2009-01-23

The dispersion-aggregation behaviors of suspended colloids in rivers and estuaries are affected by the compositions of suspended materials (i.e., clay minerals vs. organic macromolecules) and salinity. Laboratory experiments were conducted to investigate the dispersion and aggregation mechanisms of suspended particles under simulated river and estuarine conditions. The average hydrodynamic diameters of suspended particles (representing degree of aggregation) and zeta potential (representing the electrokinetic properties of suspended colloids and aggregates) were determined for systems containing suspended montmorillonite, humic acid, and/or chitin at the circumneutral pH over a range of salinity (0 - 7.2 psu). The montmorillonite-only system increased the degree of aggregation with salinity increase, as would be expected for suspended colloids whose dispersion-aggregation behavior is largely controlled by the surface electrostatic properties and van der Waals forces. When montmorillonite is combined with humic acid or chitin, the aggregation of montmorillonite was effectively inhibited. The surface interaction energy model calculations reveal that the steric repulsion, rather than the increase in electronegativity, is the primary cause for the inhibition of aggregation by the addition of humic acid or chitin. These results help explain the range of dispersion-aggregation behaviors observed in natural river and estuarine systems. It is postulated that the composition of suspended particles, specifically the availability of steric polymers such as those contained in humic acid, determine whether the river suspension is rapidly aggregated and settled or remains dispersed in suspension when it encounters increasingly saline environments of estuaries and oceans.

Molecular and Clinical Aspects of Protein Aggregation Assays in Neurodegenerative Diseases.

PubMed

Villar-Piqué, Anna; Schmitz, Matthias; Candelise, Niccolò; Ventura, Salvador; Llorens, Franc; Zerr, Inga

2018-02-10

The presence of protein deposits is a common pathological hallmark in patients suffering from neurodegenerative conditions and other proteinopathies. Deciphering the molecular basis of protein misfolding and aggregation is a crucial step towards the full comprehension of the factors that trigger the onset of these diseases and for the development of efficient therapeutical strategies. In this regard, in vitro aggregation assays for misfolded proteins offer an excellent tool to study pathological processes of protein deposition under controlled conditions, where confounders can be easily discriminated. These methods are generally cost-effective and have been proved useful in many fields, including drug discovery and clinical diagnostics. Here, we review the bases of in vitro aggregation and seeding assays, recapitulate their main applications and offer a critical evaluation of their limitations. Comprehending the molecular mechanisms behind these assays and combining them with in vivo or cell-based experiments will maximize their potential and allow the necessary improvement to overcome some of the current drawbacks.

Molecular dynamics and metadynamics simulations of electrosprayed water nanodroplets including sodium bis(2-ethylhexyl)sulfosuccinate micelles.

PubMed

Longhi, Giovanna; Ceselli, Alberto; Fornili, Sandro L; Turco Liveri, Vincenzo

2017-05-28

The behavior of aqueous solutions of sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) under conditions of electrospray ionization (ESI) has been investigated by molecular dynamics (MD) and well-tempered metadynamics (WTM) simulations at 300 K and 400 K. We have examined water droplets with initial fixed numbers of water molecules (1000) and AOT - anions (100), and with sodium cations in the range of 70-130. At 300 K, all charged droplets show the water evaporation rate increasing with the absolute value of the initial droplet charge state (Z), accompanied by ejection of an increasing number of solvated sodium ions or by expulsion of AOT - anions depending on the sign of Z and by fragmentation in the case of high |Z|. At 400 K, the water evaporation becomes more rapid and the fission process more extensive. In all cases, the AOTNa molecules, arranged as a direct micelle inside the aqueous system, undergo a rapid inversion in vacuo so that the hydrophilic heads and sodium ions surrounded by water molecules move toward the droplet interior. At the end of the 100-ns MD simulations, some water molecules remain within the aggregates at both temperatures. The subsequent metadynamics simulations accelerate the droplet evolution and show that all systems become anhydrous, in agreement with the experimental results of ESI mass spectrometry. This complete water loss is accompanied by sodium counterion emission for positively charged aggregates at 300 K. The analysis shows how the temperature and droplet charge state affect the populations of the generated surfactant aggregates, providing information potentially useful in designing future ESI experimental conditions.

Molecular dynamics and metadynamics simulations of electrosprayed water nanodroplets including sodium bis(2-ethylhexyl)sulfosuccinate micelles

NASA Astrophysics Data System (ADS)

Longhi, Giovanna; Ceselli, Alberto; Fornili, Sandro L.; Turco Liveri, Vincenzo

2017-05-01

The behavior of aqueous solutions of sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) under conditions of electrospray ionization (ESI) has been investigated by molecular dynamics (MD) and well-tempered metadynamics (WTM) simulations at 300 K and 400 K. We have examined water droplets with initial fixed numbers of water molecules (1000) and AOT- anions (100), and with sodium cations in the range of 70-130. At 300 K, all charged droplets show the water evaporation rate increasing with the absolute value of the initial droplet charge state (Z), accompanied by ejection of an increasing number of solvated sodium ions or by expulsion of AOT- anions depending on the sign of Z and by fragmentation in the case of high |Z|. At 400 K, the water evaporation becomes more rapid and the fission process more extensive. In all cases, the AOTNa molecules, arranged as a direct micelle inside the aqueous system, undergo a rapid inversion in vacuo so that the hydrophilic heads and sodium ions surrounded by water molecules move toward the droplet interior. At the end of the 100-ns MD simulations, some water molecules remain within the aggregates at both temperatures. The subsequent metadynamics simulations accelerate the droplet evolution and show that all systems become anhydrous, in agreement with the experimental results of ESI mass spectrometry. This complete water loss is accompanied by sodium counterion emission for positively charged aggregates at 300 K. The analysis shows how the temperature and droplet charge state affect the populations of the generated surfactant aggregates, providing information potentially useful in designing future ESI experimental conditions.

Self-organization of grafted polyelectrolyte layers via the coupling of chemical equilibrium and physical interactions.

PubMed

Tagliazucchi, Mario; de la Cruz, Mónica Olvera; Szleifer, Igal

2010-03-23

The competition between chemical equilibrium, for example protonation, and physical interactions determines the molecular organization and functionality of biological and synthetic systems. Charge regulation by displacement of acid-base equilibrium induced by changes in the local environment provides a feedback mechanism that controls the balance between electrostatic, van der Waals, steric interactions and molecular organization. Which strategies do responsive systems follow to globally optimize chemical equilibrium and physical interactions? We address this question by theoretically studying model layers of end-grafted polyacids. These layers spontaneously form self-assembled aggregates, presenting domains of controlled local pH and whose morphologies can be manipulated by the composition of the solution in contact with the film. Charge regulation stabilizes micellar domains over a wide range of pH by reducing the local charge in the aggregate at the cost of chemical free energy and gaining in hydrophobic interactions. This balance determines the boundaries between different aggregate morphologies. We show that a qualitatively new form of organization arises from the coupling between physical interactions and protonation equilibrium. This optimization strategy presents itself with polyelectrolytes coexisting in two different and well-defined protonation states. Our results underline the need of considering the coupling between chemical equilibrium and physical interactions due to their highly nonadditive behavior. The predictions provide guidelines for the creation of responsive polymer layers presenting self-organized patterns with functional properties and they give insights for the understanding of competing interactions in highly inhomogeneous and constrained environments such as those relevant in nanotechnology and those responsible for biological cells function.

Adaptive polymeric nanomaterials utilizing reversible covalent and hydrogen bonding

NASA Astrophysics Data System (ADS)

Neikirk, Colin

Adaptive materials based on stimuli responsive and reversible bonding moieties are a rapidly developing area of materials research. Advances in supramolecular chemistry are now being adapted to novel molecular architectures including supramolecular polymers to allow small, reversible changes in molecular and nanoscale structure to affect large changes in macroscale properties. Meanwhile, dynamic covalent chemistry provides a complementary approach that will also play a role in the development of smart adaptive materials. In this thesis, we present several advances to the field of adaptive materials and also provide relevant insight to the areas of polymer nanocomposites and polymer nanoparticles. First, we have utilized the innate molecular recognition and binding capabilities of the quadruple hydrogen bonding group ureidopyrimidinone (UPy) to prepare supramolecular polymer nanocomposites based on supramolecular poly(caprolactone) which show improved mechanical properties, but also an increase in particle aggregation with nanoparticle UPy functionalization. We also present further insight into the relative effects of filler-filler, filler-matrix, and matrix-matrix interactions using a UPy side-chain functional poly(butyl acrylate). These nanocomposites have markedly different behavior depending on the amount of UPy sidechain functionality. Meanwhile, our investigations of reversible photo-response showed that coumarin functionality in polymer nanoparticles not only facilitates light mediated aggregation/dissociation behavior, but also provides a substantial overall reduction in particle size and improvement in nanoparticle stability for particles prepared by Flash NanoPrecipitation. Finally, we have combined these stimuli responsive motifs as a starting point for the development of multiresponsive adaptive materials. The synthesis of a library of multifunctional materials has provided a strong base for future research in this area, although our initial investigations were ultimately unsuccessful due to photodegradation of the UPy moiety in chloroform solution. This thesis has provided the Priestley lab with a solid base for the further investigation of the diverse applications and unsolved science of stimuli responsive adaptive materials.

Comprehensive Computational and Experimental Analysis of Biomaterial toward the Behavior of Imidazolium-Based Ionic Liquids: An Interplay between Hydrophilic and Hydrophobic Interactions.

PubMed

Umapathi, Reddicherla; Vepuri, Suresh B; Venkatesu, Pannuru; Soliman, Mahmoud E

2017-05-11

To provide insights into the aggregation behavior, hydration tendency and variation in phase transition temperature produced by the addition of ionic liquids (ILs) to poly(N-isopropylacrylamide) (PNIPAM) aqueous solution, systematic physicochemical studies, and molecular dynamic simulations were carried out. The influence of ILs possessing the same [Cl] - anion and a set of cations [C n mim] + with increasing alkyl chain length such as 1-ethyl-3-methylimidazolium ([Emim] + ), 1-allyl-3-methylimidazolium ([Amim] + ), 1-butyl-3-methylimidazolium ([Bmim] + ), 1-hexyl-3-methylimidazolium ([Hmim] + ), 1-benzyl-3-methylimidazolium ([Bzmim] + ), and 1-decyl-3-methylimidazolium ([Dmim] + ) on the phase transition of PNIPAM was monitored by the aid of UV-visible absorption spectra, fluorescence intensity spectra, viscosity (η), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) spectroscopy. Furthermore, to interpret the direct images and surface morphologies of the PNIPAM-IL aggregates, we performed field emission scanning electron microscopy (FESEM). The overall specific ranking of ILs in preserving the hydration layer around the PNIPAM aqueous solution was [Emim][Cl] > [Amim][Cl] > [Bmim][Cl] > [Hmim][Cl] > [Bzmim][Cl] > [Dmim][Cl]. Moreover, to investigate the molecular mechanism behind the change in the lower critical solution temperature (LCST) of the polymer in the presence of the ILs, a molecular dynamics (MD) study was performed. The MD simulation has clearly shown the reduction in hydration shell of the polymer after interacting with the ILs at their respective LCST. MD study revealed significant changes in polymer conformation because of IL interactions and strongly supports the experimental observation of polymer phase transition at a temperature lower than typical LCST for all the studied ILs. The driving force for concomitant sharp configurational transition has been attributed to the displacement of water molecules on the polymer surface by the ILs because of their hydrophobic interaction with the polymer.

Treatments and compositions targeting α-synuclein: a patent review (2010-2016).

PubMed

Jęśko, Henryk; Lenkiewicz, Anna M; Adamczyk, Agata

2017-04-01

Abnormal deposition of α-synuclein (ASN) is a hallmark and possible central mechanism of Parkinson's disease and other synucleinopathies. Their therapy is currently hampered by the lack of early, screening-compatible diagnostic methods and efficient treatments. Areas covered: Patent applications related to synucleinopathies obtained from Patentscope and Espacenet databases are described against the background of current knowledge regarding the regulatory mechanisms of ASN behavior including alternative splicing, post-translational modifications, molecular interactions, aggregation, degradation, and changes in localization. Expert opinion: As the central pathological feature and possibly one of root causes in a number of neurodegenerative diseases, deregulation of ASN is a potentially optimal diagnostic and therapeutic target. Changes in total ASN may have diagnostic value, especially if non-invasive /peripheral tissue tests can be developed. Targeting the whole ASN pool for therapeutic purposes may be problematic, however. ASN mutations, truncation, and post-translational modifications have great potential value; therapeutic approaches selective towards aggregated or aggregation-prone ASN forms may lead to more successful and safe treatments. Numerous ASN interactions with signaling pathways, protein degradation and stress mechanisms widen its potential therapeutic significance dramatically. However, significant improvement in the basic knowledge on ASN is necessary to fully exploit these opportunities.

Atomistic Simulation of Single Asperity Contact

NASA Astrophysics Data System (ADS)

Philip; Kromer; Marder, Michael

2003-03-01

In the standard (Bowden and Tabor) model of friction, the macroscopic behavior of sliding results from the deformation of microscopic asperities in contact. A recent idea instead extracts macroscopic friction from the aggregate behavior of traveling, self-healing interfacial cracks: certain families of cracks are found to be mathematically forbidden, and the envelope of allowed cracks dictates the familiar Coulomb law of friction. To explore the connection between the new and traditional pictures of friction, we conducted molecular dynamics (MD) simulations of single-asperity contact subjected to an oscillatory sliding force -- a geometry important for the problem of fretting (damage due to small-scale vibratory contact). Our simulations reveal the importance of traveling interface cracks to the dynamics of slip at the interface, and illuminate the dynamics of crack initiation and suppression.

Self-assembly behavior of β-cyclodextrin and imipramine. A Free energy perturbation study

NASA Astrophysics Data System (ADS)

Sun, Tingting; Shao, Xueguang; Cai, Wensheng

2010-05-01

The self-assembly behavior of β-cyclodextrin (β-CD) and imipramine (IMI), an antidepressant drug, was investigated by molecular dynamics simulations in the gas phase and in an aqueous solution. The binding free energies for 10 possible arrangements of β-CD/IMI complexes with stoichiometries of 1:1, 2:1, and 1:2 were determined using free energy perturbation calculations. The calculations suggest that the 2:1 inclusion mode is the most energetically favored in both phases, in good agreement with experiment. The environment and the neutral and charged IMI influence the stability of the aggregates. The electrostatic interactions constitute the main contribution to the stability. The results reported in this contribution shed new light on the mechanism of association of β-CD with IMI.

Aggregate versus Individual-Level Sexual Behavior Assessment: How Much Detail Is Needed to Accurately Estimate HIV/STI Risk?

ERIC Educational Resources Information Center

Pinkerton, Steven D.; Galletly, Carol L.; McAuliffe, Timothy L.; DiFranceisco, Wayne; Raymond, H. Fisher; Chesson, Harrell W.

2010-01-01

The sexual behaviors of HIV/sexually transmitted infection (STI) prevention intervention participants can be assessed on a partner-by-partner basis: in aggregate (i.e., total numbers of sex acts, collapsed across partners) or using a combination of these two methods (e.g., assessing five partners in detail and any remaining partners in aggregate).…

When does "economic man" dominate social behavior?

PubMed

Camerer, Colin F; Fehr, Ernst

2006-01-06

The canonical model in economics considers people to be rational and self-regarding. However, much evidence challenges this view, raising the question of when "Economic Man" dominates the outcome of social interactions, and when bounded rationality or other-regarding preferences dominate. Here we show that strategic incentives are the key to answering this question. A minority of self-regarding individuals can trigger a "noncooperative" aggregate outcome if their behavior generates incentives for the majority of other-regarding individuals to mimic the minority's behavior. Likewise, a minority of other-regarding individuals can generate a "cooperative" aggregate outcome if their behavior generates incentives for a majority of self-regarding people to behave cooperatively. Similarly, in strategic games, aggregate outcomes can be either far from or close to Nash equilibrium if players with high degrees of strategic thinking mimic or erase the effects of others who do very little strategic thinking. Recently developed theories of other-regarding preferences and bounded rationality explain these findings and provide better predictions of actual aggregate behavior than does traditional economic theory.

Photoinduced orientation in natural rubber

NASA Astrophysics Data System (ADS)

de Souza, Nara C.; Cavalheri, Adriana S.; Brito, Jackeline B.; Job, Aldo E.; Oliveira, Osvaldo N.; Giacometti, José A.; Silva, Josmary R.

2012-04-01

Azobenzene molecules and their derivatives have been widely investigated for their potential applications in optical and electrooptical devices. We have prepared a new guest-host system from natural rubber (NR) impregnated with azobenzene derivative Sudan Red B (SRB). The effects of stretching and immersion time on photoinduced orientation were investigated by birefringence signal measurements. We have found that the molecular orientation increase when the samples are stretched and decrease with the increase of immersion time. The first behavior was explained by using the random coil model and the latter was attributed to increase of the aggregation of SRB into NR matrix.

INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Competition Between Self-birth and Catalyzed Death in Aggregation Growth with Catalysis Injection

NASA Astrophysics Data System (ADS)

Chen, Dan; Lin, Zhen-Quan; Sun, Yun-Fei; Ke, Jian-Hong

2009-12-01

We propose two irreversible aggregation growth models of aggregates of two distinct species (A and B) to study the interactions between virus aggregates and medicine efficacy aggregates in the virus-medicine cooperative evolution system. The A-species aggregates evolve driven by self monomer birth and B-species aggregate-catalyzed monomer death in model I and by self birth, catalyzed death, and self monomer exchange reactions in model II, while the catalyst B-species aggregates are assumed to be injected into the system sustainedly or at a periodic time-dependent rate. The kinetic behaviors of the A-species aggregates are investigated by the rate equation approach based on the mean-field theory with the self birth rate kernel IA(k) = Ik, catalyzed death rate kernel JAB(k) = Jk and self exchange rate kernel KA (k, l) = Kkl. The kinetic behaviors of the A-species aggregates are mainly dominated by the competition between the two effects of the self birth (with the effective rate I) and the catalyzed death (with the effective rate JB0), while the effects of the self exchanges of the A-species aggregates which appear in an effective rate KA0 play important roles in the cases of I > JB0 and I = JB0. The evolution behaviors of the total mass MA1(t) and the total aggregate number MA0 (t) are obtained, and the aggregate size distribution αk (t) of species A is found to approach a generalized scaling form in the case of I >= JB0 and a special modified scaling form in the case of I < JB0. The periodical evolution of the B-monomers concentration plays an exponential form of the periodic modulation.

Photoluminescence spectral reliance on aggregation order of 1,1-Bis(2'-thienyl)-2,3,4,5-tetraphenylsilole.

PubMed

Chen, Junwu; Xu, Bin; Yang, Kaixia; Cao, Yong; Sung, Herman H Y; Williams, Ian D; Tang, Ben Zhong

2005-09-15

1,1-Bis(2'-thienyl)-2,3,4,5-tetraphenylsilole (1) was prepared and characterized crystallographically. Silole 1 exhibited aggregation-induced emission (AIE) behavior like other 2,3,4,5-tetraphenylsiloles. Unexpectedly, aggregates formed in water/acetone (6:4 by volume) mixture emitted a blue light that peaked at 474 nm, while aggregates formed in the mixtures with higher water fractions emitted green light that peaked at 500 nm. Transmission electron microscopy demonstrated that the aggregates formed in the mixture with water fraction of 60% were single crystals, while aggregates that formed in the mixture with water fraction of 90% were irregular and poorly ordered particles. The unusual PL spectral reliance on aggregation order was further confirmed by PL emissions of macroscopic crystal powders and amorphous powders of the silole in the dry state. PL spectral blue shifting was observed upon aging of the poorly ordered aggregates formed in mixtures with water fractions of 70-90%, and they finally exhibited the same blue emission as the crystalline aggregates. The as-deposited thin solid film was amorphous and it could be transformed to a transparent crystalline film upon treatment in the vapor of an ethanol/water (1:1 by volume) mixture, along with PL spectral blue shifting due to changing of aggregation order. It was also found that the crystalline film showed a blue-shifted absorption spectrum relative to the amorphous film and the shift of the absorption edge of the spectra could match that of corresponding PL spectra. The FT-IR spectrum of crystal powders of 1 displayed more vibration modes compared with that of amorphous powders, suggesting the existence of different pi-overlaps or different molecular conformations. The crystals of 1-methyl-1,2,3,4,5-pentaphenylsilole and hexaphenylsilole also showed blue-shifted PL emissions of their amorphous solids, with a comparable PL spectral shift of 1. Developing of a silole solution on a TLC plate readily brought about an amorphous thin layer. Our results suggest that crystalline films of AIE-active siloles are potential emissive layers for efficient blue OLEDs with stable color and long lifetime.

Quaterrylene molecules on Ag(111): self-assembly behavior and voltage pulse induced trimer formation.

PubMed

He, Yangyong; Cai, Zeying; Shao, Jian; Xu, Li; She, Limin; Zheng, Yue; Zhong, Dingyong

2018-05-03

The self-assembly behavior of quaterrylene (QR) molecules on Ag(111) surfaces has been investigated by scanning tunneling microscopy (STM) and density functional theory (DFT) calculations. It is found that the QR molecules are highly mobile on the Ag(111) surface at 78 K. No ordered assembled structure is formed on the surface with a sub-monolayer coverage up to 0.8 monolayer due to the intermolecular repulsive interactions, whereas ordered molecular structures are observed at one monolayer coverage. According to our DFT calculations, charge transfer occurs between the substrate and the adsorbed QR molecule. As a result, out-of-plane dipoles appear at the interface, which are ascribed to the repulsive dipole-dipole interactions between the QR molecules. Furthermore, due to the planar geometry, the QR molecules exhibit relatively low diffusion barriers on Ag(111). By applying a voltage pulse between the tunneling gap, immobilization and aggregation of QR molecules take place, resulting in the formation of a triangle-shaped trimer. Our work demonstrates the ability of manipulating intermolecular repulsive and attractive interactions at the single molecular level.

Microbial Ecology of Soil Aggregation in Agroecosystems

NASA Astrophysics Data System (ADS)

Hofmockel, K. S.; Bell, S.; Tfailly, M.; Thompson, A.; Callister, S.

2017-12-01

Crop selection and soil texture influence the physicochemical attributes of the soil, which structures microbial communities and influences soil C cycling storage. At the molecular scale, microbial metabolites and necromass alter the soil environment, which creates feedbacks that influence ecosystem functions, including soil C accumulation. By integrating lab to field studies we aim to identify the molecules, organisms and metabolic pathways that control carbon cycling and stabilization in bioenergy soils. We investigated the relative influence of plants, microbes, and minerals on soil aggregate ecology at the Great Lakes Bioenergy Research experiment. Sites in WI and MI, USA have been in corn and switchgrass cropping systems for a decade. By comparing soil aggregate ecology across sites and cropping systems we are able to test the relative importance of plant, microbe, mineral influences on soil aggregate dynamics. Soil microbial communities (16S) differ in diversity and phylogeny among sites and cropping systems. FT-ICR MS revealed differences in the molecular composition of water-soluble fraction of soil organic matter for cropping systems and soil origin for both relative abundance of assigned formulas and biogeochemical classes of compounds. We found the degree of aggregation, measured by mean weighted diameter of aggregate fractions, is influenced by plant-soil interactions. Similarly, the proportion of soil aggregate fractions varied by both soil and plant factors. Differences in aggregation were reflected in differences in bacterial, but not fungal community composition across aggregate fractions, within each soil. Scanning electron microscopy revealed stark differences in mineral-organic interactions that influence the microbial niche and the accessibility of substrates within the soil. The clay soils show greater surface heterogeneity, enabling interactions with organic fraction of the soil. This is consistent with molecular data that reveal differences in the abundance of chemical classes in clay loams compared to sandy loams. Together our data demonstrate that the potential for aggregation and C storage is strongly influenced by soil mineralogy with important implications for plant-microbe interactions that mediate C biogeochemistry.

Rational Design and Synthesis of Carboxylate Gemini Surfactants with an Excellent Aggregate Behavior for Nano-La2O3 Morphology-Controllable Preparation.

PubMed

Liao, Xueming; Gao, Zhinong; Xia, Yan; Niu, Fei; Zhai, Wenzhong

2017-04-04

A series of carboxylate gemini surfactants (CGS, C n -Φ-C n , n = 12, 14, 16, 18) with diphenyl ketone as a spacer group were prepared using a simple and feasible synthetic method. These CGS exhibited an excellent surface activity with extremely low critical micelle concentration (CMC) value (approximately 10 -5 mol/L), good performance in reducing surface tension (nearly 30 mN/m), and the ability of molecular self-assembly into different aggregate morphologies via adjusting the concentrations, which is attributed to the introduction of diphenyl ketone and carboxylic acid ammonium salt in the molecular structure. Moreover, the surface activity and self-assembly ability of CGS were further optimized by tuning the length of the tail chain. These excellent properties imply that CGS can be a soft template to prepare nanomaterials, especially in morphology-controllable synthesis. By adjusting the concentration of one of CGS (C 12 -Φ-C 12 ), nano-La 2 O 3 particles with diverse morphologies were obtained, including spherical shape, bead-chain shape, rod shape, velvet-antler shape, cedar shape, and bowknot shape. This work offers a vital insight into the rational design of template agents for the development of morphology-controllable nanomaterials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wykes, M., E-mail: mikewykes@gmail.com; Parambil, R.; Gierschner, J.

Here, we present a general approach to treating vibronic coupling in molecular crystals based on atomistic simulations of large clusters. Such clusters comprise model aggregates treated at the quantum chemical level embedded within a realistic environment treated at the molecular mechanics level. As we calculate ground and excited state equilibrium geometries and vibrational modes of model aggregates, our approach is able to capture effects arising from coupling to intermolecular degrees of freedom, absent from existing models relying on geometries and normal modes of single molecules. Using the geometries and vibrational modes of clusters, we are able to simulate the fluorescencemore » spectra of aggregates for which the lowest excited state bears negligible oscillator strength (as is the case, e.g., ideal H-aggregates) by including both Franck-Condon (FC) and Herzberg-Teller (HT) vibronic transitions. The latter terms allow the adiabatic excited state of the cluster to couple with vibrations in a perturbative fashion via derivatives of the transition dipole moment along nuclear coordinates. While vibronic coupling simulations employing FC and HT terms are well established for single-molecules, to our knowledge this is the first time they are applied to molecular aggregates. Here, we apply this approach to the simulation of the low-temperature fluorescence spectrum of para-distyrylbenzene single-crystal H-aggregates and draw comparisons with coarse-grained Frenkel-Holstein approaches previously extensively applied to such systems.« less

Chaperones in Polyglutamine Aggregation: Beyond the Q-Stretch

PubMed Central

Kuiper, E. F. E.; de Mattos, Eduardo P.; Jardim, Laura B.; Kampinga, Harm H.; Bergink, Steven

2017-01-01

Expanded polyglutamine (polyQ) stretches in at least nine unrelated proteins lead to inherited neuronal dysfunction and degeneration. The expansion size in all diseases correlates with age at onset (AO) of disease and with polyQ protein aggregation, indicating that the expanded polyQ stretch is the main driving force for the disease onset. Interestingly, there is marked interpatient variability in expansion thresholds for a given disease. Between different polyQ diseases the repeat length vs. AO also indicates the existence of modulatory effects on aggregation of the upstream and downstream amino acid sequences flanking the Q expansion. This can be either due to intrinsic modulation of aggregation by the flanking regions, or due to differential interaction with other proteins, such as the components of the cellular protein quality control network. Indeed, several lines of evidence suggest that molecular chaperones have impact on the handling of different polyQ proteins. Here, we review factors differentially influencing polyQ aggregation: the Q-stretch itself, modulatory flanking sequences, interaction partners, cleavage of polyQ-containing proteins, and post-translational modifications, with a special focus on the role of molecular chaperones. By discussing typical examples of how these factors influence aggregation, we provide more insight on the variability of AO between different diseases as well as within the same polyQ disorder, on the molecular level. PMID:28386214

Final technical report for project titled Quantitative Characterization of Cell Aggregation/Adhesion as Predictor for Distribution and Transport of Microorganisms in Subsurface Environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, April Z.; Wan, Kai-tak

This project aims to explore and develop enabling methodology and techniques for nano-scale characterization of microbe cell surface contact mechanics, interactions and adhesion quantities that allow for identification and quantification of indicative properties related to microorganism migration and transport behavior in porous media and in subsurface environments. Microbe transport has wide impact and therefore is of great interest in various environmental applications such as in situ or enhanced subsurface bioremediation,filtration processes for water and wastewater treatments and protection of drinking water supplies. Although great progress has been made towards understanding the identities and activities of these microorganisms in the subsurface,more » to date, little is known of the mechanisms that govern the mobility and transport of microorganisms in DOE’s contaminated sites, making the outcomes of in situ natural attenuation or contaminant stability enhancement unpredictable. Conventionally, movement of microorganisms was believed to follows the rules governing solute (particle) transport. However, recent studies revealed that cell surface properties, especially those pertaining to cell attachment/adhesion and aggregation behavior, can cause the microbe behavior to deviate from non-viable particles and hence greatly influence the mobility and distribution of microorganisms in porous media.This complexity highlights the need to obtain detailed information of cell-cell and cell-surface interactions in order to improve and refine the conceptual and quantitative model development for fate and transport of microorganisms and contaminant in subsurface. Traditional cell surface characterization methods are not sufficient to fully predict the deposition rates and transport behaviors of microorganism observed. A breakthrough of methodology that would allow for quantitative and molecular-level description of intrinsic cell surface properties indicative for cell-surface interactions is essential for the field. To tackle this, we have developed a number of new Bio-nanomechanical techniques, including reflection interference contrast microscopy (RICM) and bio-AFM (Atomic Force Microscopy), for cell adhesion-detachment measurement of the long-range surface interactions, in combination with mathematical modeling, which would allow us to characterize the mechanical behavior from single cell to multi-cell aggregate, critical thresholds for large scale coaggregation and transportation of cells and aggregates in the presence of long range inter-surface forces etc. Although some technical and mathematical challenges remain, the preliminary results promise great breakthrough potential. In this study, we investigated the cellular surface characteristics of representative bio-remediating microorganisms relevant to DOE IFRC (Integrated Field-Scale Subsurface Research Challenges) sites and their transport behaviors in porous media, aiming to draw a groundbreaking correlation between the micro-scale genetic and biological origin-based cell surface properties, the consequent mechanical adhesion and aggregation behaviors, and the macro-scale microbial mobility and retention in porous media, which are unavailable in the literature. The long-term goal is to significantly improve the mechanistic and quantitative understanding of microbial mobility, sorption, and transport within reactive transport models as needed to manipulate subsurface contaminant fate and transport predictions.« less

Self-aggregation of cationically modified poly(ε-caprolactone)2-co-poly(ethylene glycol) copolymers: Effect of cationic grafting ligand and poly(ε-caprolactone) chain length.

PubMed

Charoongchit, Pimchanok; Suksiriworapong, Jiraphong; Sripha, Kittisak; Mao, Shirui; Sapin-Minet, Anne; Maincent, Philippe; Junyaprasert, Varaporn Buraphacheep

2017-03-01

Cationic copolymers have been attractive to investigate due to their potential to complexation with anionic drugs and expected to use in the pharmaceutical application. In this study, the modified poly(ε-caprolactone) 2 -co-poly(ethylene glycol) copolymers (P(CL) 2 -PEG) were successfully synthesized by click reaction. The amount of small molecular cationic ligand, propargyltrimethyl ammonium iodide, was varied and grafted onto various mole ratios of P(CL) to PEG. The effects of P(CL) chain length and amount of the grafting cationic ligand on physicochemical properties of polymers and particles were studied. The number-average molecular weights of the copolymers grafted with cationic ligand were found ranging between 10,000 and 23,000g/mol as investigated by NMR. From DSC study, the results showed that the grafting ligand affected thermal behaviors of the copolymers by increasing the glass transition temperature and decreasing the melting temperature of the copolymers. Furthermore, these cationic copolymers could self-aggregate with their critical aggregation concentration depending on mole ratios of hydrophilic to hydrophobic portions. The particles containing higher amounts of the cationic ligand tended to aggregate in both acidic and basic pH environment and at high salt concentration. Additionally, particle size, size distribution (PdI), and morphology of self-assembling particles varied depending on P(CL) chain length and the amount of the grafting cationic ligand. The synthesized cationic copolymer showed a capability to encapsulate a high negatively charged drug, enoxaparin, with an encapsulation efficiency of 87%. After drug incorporation, the particles substantially changed in size, shape, PdI, and zeta potential to become more suitable for drug delivery. These cationic copolymers with flexible properties will be the candidate for further development as carriers for the delivery of negatively charged drugs. Copyright © 2016. Published by Elsevier B.V.

Molecular investigation on the binding of Cd(II) by the binary mixtures of montmorillonite with two bacterial species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Huihui; Qu, ChenChen; Liu, Jing

Bacteria and phyllosilicate commonly coexist in the natural environment, producing various bacteria–clay complexes that are capable of immobilizing heavy metals, such as cadmium, via adsorption. However, the molecular binding mechanisms of heavy metals on these complex aggregates still remain poorly understood. This study investigated Cd adsorption on Gram-positive B. subtilis, Gram-negative P. putida and their binary mixtures with montmorillonite (Mont) using the Cd K-edge x-ray absorption spectroscopy (XAS) and isothermal titration calorimetry (ITC). We observed a lower adsorptive capacity for P. putida than B. subtilis, whereas P. putida–Mont and B. subtilis–Mont mixtures showed nearly identical Cd adsorption behaviors. EXAFS fitsmore » and ITC measurements demonstrated more phosphoryl binding of Cd in P. putida. The decreased coordination of C atoms around Cd and the reduced adsorption enthalpies and entropies for the binary mixtures compared to that for individual bacteria suggested that the bidentate Cd-carboxyl complexes in pure bacteria systems were probably transformed into monodentate complexes that acted as ionic bridging structure between bacteria and motmorillonite. This study clarified the binding mechanism of Cd at the bacteria–phyllosilicate interfaces from a molecular and thermodynamic view, which has an environmental significance for predicting the chemical behavior of trace elements in complex mineral–organic systems.« less

Aggregation of montmorillonite and organic matter in aqueous media containing artificial seawater

PubMed Central

2009-01-01

Background The dispersion-aggregation behaviors of suspended colloids in rivers and estuaries are affected by the compositions of suspended materials (i.e., clay minerals vs. organic macromolecules) and salinity. Laboratory experiments were conducted to investigate the dispersion and aggregation mechanisms of suspended particles under simulated river and estuarine conditions. The average hydrodynamic diameters of suspended particles (representing degree of aggregation) and zeta potential (representing the electrokinetic properties of suspended colloids and aggregates) were determined for systems containing suspended montmorillonite, humic acid, and/or chitin at the circumneutral pH over a range of salinity (0 – 7.2 psu). Results The montmorillonite-only system increased the degree of aggregation with salinity increase, as would be expected for suspended colloids whose dispersion-aggregation behavior is largely controlled by the surface electrostatic properties and van der Waals forces. When montmorillonite is combined with humic acid or chitin, the aggregation of montmorillonite was effectively inhibited. The surface interaction energy model calculations reveal that the steric repulsion, rather than the increase in electronegativity, is the primary cause for the inhibition of aggregation by the addition of humic acid or chitin. Conclusion These results help explain the range of dispersion-aggregation behaviors observed in natural river and estuarine systems. It is postulated that the composition of suspended particles, specifically the availability of steric polymers such as those contained in humic acid, determine whether the river suspension is rapidly aggregated and settled or remains dispersed in suspension when it encounters increasingly saline environments of estuaries and oceans. PMID:19166595

Pigment granule translocation in red ovarian chromatophores from the palaemonid shrimp Macrobrachium olfersi (Weigmann, 1836): functional roles for the cytoskeleton and its molecular motors.

PubMed

Milograna, Sarah Ribeiro; Ribeiro, Márcia Regina; Baqui, Munira Muhammad Abdel; McNamara, John Campbell

2014-12-01

The binding of red pigment concentrating hormone (RPCH) to membrane receptors in crustacean chromatophores triggers Ca²⁺/cGMP signaling cascades that activate cytoskeletal motors, driving pigment granule translocation. We investigate the distributions of microfilaments and microtubules and their associated molecular motors, myosin and dynein, by confocal and transmission electron microscopy, evaluating a functional role for the cytoskeleton in pigment translocation using inhibitors of polymer turnover and motor activity in vitro. Microtubules occupy the chromatophore cell extensions whether the pigment granules are aggregated or dispersed. The inhibition of microtubule turnover by taxol induces pigment aggregation and inhibits re-dispersion. Phalloidin-FITC actin labeling, together with tannic acid fixation and ultrastructural analysis, reveals that microfilaments form networks associated with the pigment granules. Actin polymerization induced by jasplaquinolide strongly inhibits RPCH-induced aggregation, causes spontaneous pigment dispersion, and inhibits pigment re-dispersion. Inhibition of actin polymerization by latrunculin-A completely impedes pigment aggregation and re-dispersion. Confocal immunocytochemistry shows that non-muscle myosin II (NMMII) co-localizes mainly with pigment granules while blebbistatin inhibition of NMMII strongly reduces the RPCH response, also inducing spontaneous pigment dispersion. Myosin II and dynein also co-localize with the pigment granules. Inhibition of dynein ATPase by erythro-9-(2-hydroxy-3-nonyl) adenine induces aggregation, inhibits RPCH-triggered aggregation, and inhibits re-dispersion. Granule aggregation and dispersion depend mainly on microfilament integrity although microtubules may be involved. Both cytoskeletal polymers are functional only when subunit turnover is active. Myosin and dynein may be the molecular motors that drive pigment aggregation. These mechanisms of granule translocation in crustacean chromatophores share various features with those of vertebrate pigment cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity.

PubMed

Yamashita, Arisa; Hiraki, Yuri; Yamazaki, Tetsuo

2017-06-10

αB-crystallin (αBC) is a small heat shock protein. Mutations in the αBC gene are linked to α-crystallinopathy, a hereditary myopathy histologically characterized by intracellular accumulation of protein aggregates. The disease-causing R120G αBC mutant, harboring an arginine-to-glycine replacement at position 120, is an aggregate-prone protein. We previously showed that the R120G mutant's aggregation in HeLa cells was prevented by enforced expression of αBC on the endoplasmic reticulum (ER). To elucidate the molecular nature of the preventive effect on the R120G mutant, we isolated proteins binding to ER-anchored αBC (TMαBC). The ER transmembrane CLN6 protein was identified as a TMαBC's binder. CLN6 knockdown in HeLa cells attenuated TMαBC's anti-aggregate activity against the R120G mutant. Conversely, CLN6 overexpression enhanced the activity, indicating that CLN6 operates as a downstream effector of TMαBC. CLN6 physically interacted with the R120G mutant, and repressed its aggregation in HeLa cells even when TMαBC was not co-expressed. Furthermore, CLN6's antagonizing effect on the R120G mutant was compromised upon treatment with a lysosomal inhibitor, suggesting CLN6 requires the intact autophagy-lysosome system to prevent the R120G mutant from aggregating. We hence conclude that CLN6 is not only a molecular entity of the anti-aggregate activity conferred by the ER manipulation using TMαBC, but also serves as a potential target of therapeutic interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

A thermal after-effect of UV irradiation of muscle glycogen phosphorylase b

PubMed Central

Eronina, Tatiana B.; Chebotareva, Natalia A.; Kleymenov, Sergey Yu.; Shubin, Vladimir V.; Kurganov, Boris I.

2017-01-01

Different test systems are used to characterize the anti-aggregation efficiency of molecular chaperone proteins and of low-molecular-weight chemical chaperones. Test systems based on aggregation of UV-irradiated protein are of special interest because they allow studying the protective action of different agents at physiological temperatures. The kinetics of UV-irradiated glycogen phosphorylase b (UV-Phb) from rabbit skeletal muscle was studied at 37°C using dynamic light scattering in a wide range of protein concentrations. It has been shown that the order of aggregation with respect to the protein is equal to unity. A conclusion has been made that the rate-limiting stage of the overall process of aggregation is heat-induced structural reorganization of a UV-Phb molecule, which contains concealed damage. PMID:29216272

Three-dimensional Myoblast Aggregates--Effects of Modeled Microgravity

NASA Technical Reports Server (NTRS)

Byerly, Diane; Sognier, M. A.; Marquette, M. L.

2006-01-01

The overall objective of these studies is to elucidate the molecular and cellular alterations that contribute to muscle atrophy in astronauts caused by exposure to microgravity conditions in space. To accomplish this, a three-dimensional model test system was developed using mouse myoblast cells (C2C12). Myoblast cells were grown as three-dimensional aggregates (without scaffolding or other solid support structures) in both modeled microgravity (Rotary Cell Culture System, Synthecon, Inc.) and at unit gravity in coated Petri dishes. Evaluation of H&E stained thin sections of the aggregates revealed the absence of any necrosis. Confocal microscopy evaluations of cells stained with the Live/Dead assay (Molecular Probes) confirmed that viable cells were present throughout the aggregates with an average of only three dead cells observed per aggregate. Preliminary results from gene array analysis (Affymetrix chip U74Av2) showed that approximately 14% of the genes were down regulated (decreased more than 3 fold) and 4% were upregulated in cells exposed to modeled microgravity for 12 hours compared to unit gravity controls. Additional studies using fluorescent phallacidin revealed a decrease in F-actin in the cells exposed to modeled microgravity compared to unit gravity. Myoblast cells grown as aggregates in modeled microgravity exhibited spontaneous differentiation into syncitia while no differentiation was seen in the unit gravity controls. These studies show that 1)the model test system developed is suitable for assessing cellular and molecular alterations in myoblasts; 2) gene expression alterations occur rapidly (within 12 hours) following exposure to modeled microgravity; and 3) modeled microgravity conditions stimulated myoblast cell differentiation. Achieving a greater understanding of the molecular alterations leading to muscle atrophy will eventually enable the development of cell-based countermeasures, which may be valuable for treatment of muscle diseases on Earth and future space explorations.

Simulation of Ionic Aggregation and Ion Dynamics in Model Ionomers

NASA Astrophysics Data System (ADS)

Frischknecht, Amalie L.

2012-02-01

Ionomers, polymers containing a small fraction of covalently bound ionic groups, are of interest as possible electrolytes in batteries. A single-ion conducting polymer electrolyte would be safer and have higher efficiency than the currently-used liquid electrolytes. However, to date ionomeric materials do not have sufficiently high conductivities for practical application. This is most likely because the ions tend to form aggregates, leading to slow ion transport. A key question is therefore how molecular structure affects the ionic aggregation and ion dynamics. To probe these structure-property relationships, we have performed molecular simulations of a set of recently synthesized poly(ethylene-co-acrylic acid) copolymers and ionomers, with a focus on the morphology of the ionic aggregates. The ionomers have a precise, constant spacing of charged groups, making them ideal for direct comparisons with simulations. Ab initio calculations give insight into the expected coordination of cations with fragments of the ionomers. All-atom molecular dynamics (MD) simulations of the ionomer melt show aggregation of the ionic groups into extended string-like clusters. An extensive set of coarse-grained molecular dynamics simulations extend the results to longer times and larger length scales. The structure factors calculated from the MD simulations compare favorably with x-ray scattering data. Furthermore, the simulations give a detailed picture of the sizes, shapes, and composition of the ionic aggregates, and how they depend on polymer architecture. Implications for ion transport will be discussed. [Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Ionic liquid structure, dynamics, and electrosorption in carbon electrodes with bimodal pores and heterogeneous surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dyatkin, Boris; Osti, Naresh C.; Zhang, Yu

In this paper, we investigate the aggregation, diffusion, and resulting electrochemical behavior of ionic liquids inside carbon electrodes with complex pore architectures and surface chemistries. Carbide-derived carbons (CDCs) with bimodal porosities and defunctionalized or oxidized electrode surfaces served as model electrode materials. Our goal was to obtain a fundamental understanding of room-temperature ionic liquid ion orientation, mobility, and electrosorption behavior. Neat 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide confined in CDCs was studied using an integrated experimental and modeling approach, consisting of quasielastic neutron scattering, small-angle neutron scattering, X-ray pair distribution function analysis, and electrochemical measurements, which were combined with molecular dynamics simulations. Our analysismore » shows that surface oxygen groups increase the diffusion of confined electrolytes. Consequently, the ions become more than twice as mobile in oxygen-rich pores. Although greater self-diffusion of ions translates into higher electrochemical mobilities in oxidized pores, bulk-like behavior of ions dominates in the larger mesopores and increases the overall capacitance in defunctionalized pores. Experimental results highlight strong confinement and surface effects of carbon electrodes on electrolyte behavior, and molecular dynamics simulations yield insight into diffusion and capacitance differences in specific pore regions. Finally, we demonstrate the significance of surface defects on electrosorption dynamics of complex electrolytes in hierarchical pore architectures of supercapacitor electrodes.« less

Ionic liquid structure, dynamics, and electrosorption in carbon electrodes with bimodal pores and heterogeneous surfaces

DOE PAGES

Dyatkin, Boris; Osti, Naresh C.; Zhang, Yu; ...

2017-12-05

In this paper, we investigate the aggregation, diffusion, and resulting electrochemical behavior of ionic liquids inside carbon electrodes with complex pore architectures and surface chemistries. Carbide-derived carbons (CDCs) with bimodal porosities and defunctionalized or oxidized electrode surfaces served as model electrode materials. Our goal was to obtain a fundamental understanding of room-temperature ionic liquid ion orientation, mobility, and electrosorption behavior. Neat 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide confined in CDCs was studied using an integrated experimental and modeling approach, consisting of quasielastic neutron scattering, small-angle neutron scattering, X-ray pair distribution function analysis, and electrochemical measurements, which were combined with molecular dynamics simulations. Our analysismore » shows that surface oxygen groups increase the diffusion of confined electrolytes. Consequently, the ions become more than twice as mobile in oxygen-rich pores. Although greater self-diffusion of ions translates into higher electrochemical mobilities in oxidized pores, bulk-like behavior of ions dominates in the larger mesopores and increases the overall capacitance in defunctionalized pores. Experimental results highlight strong confinement and surface effects of carbon electrodes on electrolyte behavior, and molecular dynamics simulations yield insight into diffusion and capacitance differences in specific pore regions. Finally, we demonstrate the significance of surface defects on electrosorption dynamics of complex electrolytes in hierarchical pore architectures of supercapacitor electrodes.« less

Effect of molecular conformation on the mechanofluorochromic properties based on DDIF

NASA Astrophysics Data System (ADS)

Mai, Runsheng; Peng, Huojun; Meng, Yuying; Chang, Xinyue; Jiang, Yue; Gao, Jinwei; Zhou, Guofu; Liu, Jun-ming

2017-07-01

Mechanofluorochromic (MFC) materials are smart materials in that their absorption and/or emission can respond to mechanical stimuli. They have received much attention recently. Although there have been several new material systems designed, little work has been done regarding the influence of molecular conformation on MFC properties. Herein, to disclose the relationship between molecular conformation and MFC properties, two molecules based on a 6, 12-Dihydro-6, 12-diaza-indeno[1,2-b]fluorine (DDIF) building block with thienyl linker, BDDIF-Th and BDDIF-BTh, have been designed and synthesized. Optical and electrochemical properties have been studied by UV-vis spectrometer and cyclic voltammetry measurements. Weak aggregation-induced emission (AIE) phenomena were obtained in the tetrahydrofuran (THF)/water solution. MFC behaviors suggest that BDDIF-Th is more sensible to the external mechanical forces than BDDIF-BTh. The color change could be attributed to the appearance of new emission peak instead of a bathochromic or hypsochromic effect. Theoretical calculations reveal that MFC performance is highly related to the molecular conformation, meaning that the BDDIF-BTh with perpendicular conformation is more difficult to flatten than the comparatively planar BDDIF-Th.

Effect of molecular weight of polyethylene glycol on the rheological properties of fumed silica-polyethylene glycol shear thickening fluid

NASA Astrophysics Data System (ADS)

Singh, Mansi; Verma, Sanjeev K.; Biswas, Ipsita; Mehta, Rajeev

2018-05-01

The steady-shear viscosity and dynamic visco-elastic behavior of suspensions of 20 wt% fumed silica-polyethylene glycol (PEG200) shear thickening fluid (STF) with different concentrations of various molecular weight PEG (4600, 6000 and 10000) has been studied. The results demonstrate that with an increase in the molecular weight of dispersing medium, the shear thickening parameters are significantly enhanced. In steady-state rheology, addition of PEG6000 as an additive results in high shear thickening at both low and high temperatures whereas in dynamic state, PEG4600 gives high values of all dynamic parameters. Additionally, long polymer can interconnect several particles, acting as cross-links which explain the mechanism of the enhancement in viscosity. Interestingly, compositions having PEG10000 as additive exhibits shear thinning rheology. Long polymer chains increases hydrodynamic forces thus aggregation of particles increases. Also, the results demonstrate the effect of high molecular weight PEGs on the elasticity and stability of the STF, which is important with regard to high impact resisting applications.

Absorption and resonance Raman characteristics of β-carotene in water-ethanol mixtures, emulsion and hydrogel

NASA Astrophysics Data System (ADS)

Meinhardt-Wollweber, Merve; Suhr, Christian; Kniggendorf, Ann-Kathrin; Roth, Bernhard

2018-05-01

Absorption or resonance Raman scattering are often used to identify and even quantify carotenoids in situ. We studied the absorption spectra, the Raman spectra and their resonance behavior of β-carotene in different molecular environments set up as mixtures from lipid (emulsion) and non-polar (ethanol) solvents and a polar component (water) with regard to their application as references for in situ measurement. We show how both absorption profiles and resonance spectra of β-carotene strongly depend on the molecular environment. Most notably, our data suggests that the characteristic bathochromic absorption peak of J-aggregates does not contribute to carotenoid resonance conditions, and show how the Raman shift of the C=C stretching mode is dependent on both, the molecular environment and the excitation wavelength. Overall, the spectroscopic data collected here is highly relevant for the interpretation of in situ spectroscopic data in terms of carotenoid identification and quantification by resonance Raman spectroscopy as well as the preparation of reference samples. In particular, our data promotes careful consideration of appropriate molecular environment for reference samples.

Learning To Fold Proteins Using Energy Landscape Theory

PubMed Central

Schafer, N.P.; Kim, B.L.; Zheng, W.; Wolynes, P.G.

2014-01-01

This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy landscape theory of protein folding. We also present a review of the results of the AMH/AMC/AMW/AWSEM family of coarse-grained molecular dynamics protein folding models to illustrate the points covered in the first part of the article. Accurate coarse-grained structure prediction models can be used to investigate a wide range of conceptual and mechanistic issues outside of protein structure prediction; specifically, the paper concludes by reviewing how AWSEM has in recent years been able to elucidate questions related to the unusual kinetic behavior of artificially designed proteins, multidomain protein misfolding, and the initial stages of protein aggregation. PMID:25308991

In Situ Observations of Electric-Field Induced Nanoparticle Aggregation

NASA Astrophysics Data System (ADS)

Woehl, T. J.; Browning, N. D.; Ristenpart, W. D.

2010-11-01

Nanoparticles have been widely observed to aggregate laterally on electrodes in response to applied electric fields. The mechanism driving this behavior, however, is unclear. Several groups have interpreted the aggregation in terms of electrohydrodynamic or electroosmotic fluid motion, but little corroborating evidence has been presented. Notably, work to date has relied on post situ observations using electron microscopy. Here we present a fluorescence microscopy technique to track the dynamics of nanoparticle aggregation in situ. Fluorescent 20-nm polystyrene nanoparticles are observed to form optically visible aggregates in response to an applied AC field. Although single particle resolution is lost, the existence of aggregates on the electrode surface is marked by growing clusters of increasingly bright intensity. We present a systematic investigation of the effects of applied potential and frequency on the aggregation rate, and we interpret the behavior in terms of a mechanism based on electrically induced convective flow.

Evolving gene regulation networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system

PubMed Central

Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L.

2014-01-01

Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs, their localized patterning into remarkably different cell types aggregated into variably sized parts of the central nervous system begin to emerge. Insights at the cellular and molecular level begin to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early and not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system. PMID:25416504

Evolving gene regulatory networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system.

PubMed

Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L

2015-01-01

Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs and their localized patterning leading to remarkably different cell types aggregated into variably sized parts of the central nervous system have begun to emerge. Insights at the cellular and molecular level have begun to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early, which were not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system.

Enzyme-specific sensors via aggregation of charged p-phenylene ethynylenes.

PubMed

Hill, Eric H; Zhang, Yue; Evans, Deborah G; Whitten, David G

2015-03-11

Chemical and biological sensors are sought for their ability to detect enzymes as biomarkers for symptoms of various disorders, or the presence of chemical pollutants or poisons. p-Phenylene ethynylene oligomers with pendant charged groups have been recently shown to have ideal photophysical properties for sensing. In this study, one anionic and one cationic oligomer are combined with substrates that are susceptible to enzymatic degradation by phospholipases or acetylcholinesterases. The photophysical properties of the J-aggregated oligomers with the substrate are ideal for sensing, with fluorescence quantum yields of the sensors enhanced between 30 and 66 times compared to the oligomers without substrate. The phospholipase sensor was used to monitor the activity of phospholipase A1 and A2 and obtain kinetic information, though phospholipase C did not degrade the sensor. The acetylcholinesterase sensor was used to monitor enzyme activity and was also used to detect the inhibition of acetylcholinesterase by three different inhibitors. Phospholipase A2 is a biomarker for heart and circulatory disease, and acetylcholinesterase is a biomarker for Alzheimer's, and indicative of exposure to certain pesticides and nerve agents. This work shows that phenylene ethynylene oligomers can be tailored to enzyme-specific sensors by careful selection of substrates that induce formation of a molecular aggregate, and that the sensing of enzymes can be extended to enzyme kinetics and detection of inhibition. Furthermore, the aggregates were studied through all-atom molecular dynamics, providing a molecular-level view of the formation of the molecular aggregates and their structure.

The effects of vibronic coupling on the photophysics of pi-conjugated oligomers and polymers

NASA Astrophysics Data System (ADS)

Yamagata, Hajime

A theoretical model describing photophysics of pi-conjugated aggregates, such as molecular crystals and polymer thin films, is developed. A Holstein-like Hamiltonian expressed with a multi-particle basis set is used to evaluate absorption and photoluminescence (PL) spectra. An analysis with line strength ratio proves to be a powerful diagnostic tool to obtain additional spectral signatures with which to distinguish H- vs. J-aggregation. For the H-aggregates absorption peak ratio, A 0-0/A 0-1, diminishes as the excitonic coupling increases. Also the PL peak ratio, I 0-0/I 0-1, is zero at T=0K with no disorder and the value increases as temperature and disorder increase. By contrast the J-aggregates show the opposite trends. Furthermore we will show the PL peak ratio provides a direct measurement of the exciton coherence length for a linear J-aggregate and could be expressed as I0-0/I 0-1 = Ncoh/gamma2. We will also show that it is inversely proportional to square root of temperature (T-1/2). Applying our theory to the herringbone style oligoacene molecular crystals, we show the lowest singlet exciton states are highly influenced by charge transfer (CT) states and the well known energetic gap in two polarized absorption spectra, so called Davydov Splitting (DS), is a product of the interaction. We have successfully reproduced the DS for all three oligoacenes without any free parameters. Inspired by the CT contribution in oligoacene crystals, we further develop Wannier-Mott exciton model and apply to disorder-free polydiacetylene (PDA) quantum wires, which have been shown to be extremely emissive. We will show the quantum wire is a J-aggregate and we once again derive the peak ratio and the coherence size relation, I0-0/I 0-1 = kappaNcoh/gamma 2, where kappa is a prefactor close to unity. Typical photophysical properties of polymer pi-stacks such as those occurring in P3HT films are well explained by the simple linear H-aggregate model. However several groups have started seeing more J-like behaviors amongst "improved" (less disordered) polymer films such as increased values of A 0-0/A 0-1 and I 0-0/I 0-1 and higher radiative rates. With the new perception of a single polymer chain being a J-aggregate, we apply our new theory to pi-stack of polymer chains. We call this HJ-aggregate model since the interchain interaction induces H-aggregation. In the study we show a competition between intrachain and interchain interactions that leads to unique photophysical features. The new model is capable of explaining a wide range of polymer systems and most importantly the theory uncovers the mechanism of the improved polymer films; reducing disorder urges increasing intrachain reactions within each chain, thus enhancing more J-like spectral features.

Dynamics of cellular level function and regulation derived from murine expression array data.

PubMed

de Bivort, Benjamin; Huang, Sui; Bar-Yam, Yaneer

2004-12-21

A major open question of systems biology is how genetic and molecular components interact to create phenotypes at the cellular level. Although much recent effort has been dedicated to inferring effective regulatory influences within small networks of genes, the power of microarray bioinformatics has yet to be used to determine functional influences at the cellular level. In all cases of data-driven parameter estimation, the number of model parameters estimable from a set of data is strictly limited by the size of that set. Rather than infer parameters describing the detailed interactions of just a few genes, we chose a larger-scale investigation so that the cumulative effects of all gene interactions could be analyzed to identify the dynamics of cellular-level function. By aggregating genes into large groups with related behaviors (megamodules), we were able to determine the effective aggregate regulatory influences among 12 major gene groups in murine B lymphocytes over a variety of time steps. Intriguing observations about the behavior of cells at this high level of abstraction include: (i) a medium-term critical global transcriptional dependence on ATP-generating genes in the mitochondria, (ii) a longer-term dependence on glycolytic genes, (iii) the dual role of chromatin-reorganizing genes in transcriptional activation and repression, (iv) homeostasis-favoring influences, (v) the indication that, as a group, G protein-mediated signals are not concentration-dependent in their influence on target gene expression, and (vi) short-term-activating/long-term-repressing behavior of the cell-cycle system that reflects its oscillatory behavior.

Aggregate nanostructures of organic molecular materials.

PubMed

Liu, Huibiao; Xu, Jialiang; Li, Yongjun; Li, Yuliang

2010-12-21

Conjugated organic molecules are interesting materials because of their structures and their electronic, electrical, magnetic, optical, biological, and chemical properties. However, researchers continue to face great challenges in the construction of well-defined organic compounds that aggregate into larger molecular materials such as nanowires, tubes, rods, particles, walls, films, and other structural arrays. Such nanoscale materials could serve as direct device components. In this Account, we describe our recent progress in the construction of nanostructures formed through the aggregation of organic conjugated molecules and in the investigation of the optical, electrical, and electronic properties that depend on the size or morphology of these nanostructures. We have designed and synthesized functional conjugated organic molecules with structural features that favor assembly into aggregate nanostructures via weak intermolecular interactions. These large-area ordered molecular aggregate nanostructures are based on a variety of simpler structures such as fullerenes, perylenes, anthracenes, porphyrins, polydiacetylenes, and their derivatives. We have developed new methods to construct these larger structures including organic vapor-solid phase reaction, natural growth, association via self-polymerization and self-organization, and a combination of self-assembly and electrochemical growth. These methods are both facile and reliable, allowing us to produce ordered and aligned aggregate nanostructures, such as large-area arrays of nanowires, nanorods, and nanotubes. In addition, we can synthesize nanoscale materials with controlled properties. Large-area ordered aggregate nanostructures exhibit interesting electrical, optical, and optoelectronic properties. We also describe the preparation of large-area aggregate nanostructures of charge transfer (CT) complexes using an organic solid-phase reaction technique. By this process, we can finely control the morphologies and sizes of the organic nanostructures on wires, tubes, and rods. Through field emission studies, we demonstrate that the films made from arrays of CT complexes are a new kind of cathode materials, and we systematically investigate the effects of size and morphology on electrical properties. Low-dimension organic/inorganic hybrid nanostructures can be used to produce new classes of organic/inorganic solid materials with properties that are not observed in either the individual nanosize components or the larger bulk materials. We developed the combined self-assembly and templating technique to construct various nanostructured arrays of organic and inorganic semiconductors. The combination of hybrid aggregate nanostructures displays distinct optical and electrical properties compared with their individual components. Such hybrid structures show promise for applications in electronics, optics, photovoltaic cells, and biology. In this Account, we aim to provide an intuition for understanding the structure-function relationships in organic molecular materials. Such principles could lead to new design concepts for the development of new nonhazardous, high-performance molecular materials on aggregate nanostructures.

Self-assembly of a triangle-shaped, hexaplatinum-incorporated, supramolecular amphiphile in solution and at interfaces.

PubMed

Maran, Umamageswaran; Britt, David; Fox, Christopher B; Harris, Joel M; Orendt, Anita M; Conley, Hiram; Davis, Robert; Hlady, Vladamir; Stang, Peter J

2009-08-24

The self-assembly and characterization of a novel supramolecular amphiphile built from a new 60 degree amphiphilic precursor that incorporates hydrophilic platinum(II) metals and hydrophobic dioctadecyloxy chains is reported. The amphiphilic macrocycle and its precursor compound have been characterized by multinuclear NMR spectroscopy, ESI-MS, and other standard techniques. The coacervate morphology of the amphiphile at the liquid-liquid interface has been studied by using confocal optical microscopy and in situ Raman spectroscopy. The self-assembly of the amphiphilic macrocycle at the air-water interface has been investigated through Langmuir-trough techniques. The study indicates the possible formation of surface micelle-like aggregates. The disparity between the experimental molecular areas and those derived from molecular models support the idea of aggregation. AFM images of the surface aggregates show the formation of a flat topology with arbitrary ridgelike patterns. Reasonable molecular-packing arrangements are proposed to explain the molecular organization within the observed structures.

Replica exchange molecular dynamics simulation of cross-fibrillation of IAPP and PrP106-126.

PubMed

Chua, Khi Pin; Chew, Lock Yue; Mu, Yuguang

2016-08-01

Aggregation of proteins into amyloid is the central hallmark of a number of protein diseases. Most studies were carried out on the aggregation between proteins of similar species. However, it was observed that some patients with certain protein disease can easily acquire another unrelated protein disease. As such, it is also important to examine aggregation between proteins of different species. Usually aggregation between proteins of the same species can be attributed to the similarity between their respective amino acid sequences. In this article, we were motivated by an experimental study of aggregation between amylin (Islet Amyloid Polypeptide, IAPP) and prion106-126 (PrP106-126) fragment (JACS, 2013, 135, 13582-9). It was found that the two non-homologous peptides can aggregate quickly to form fibrils in the presence of negatively charged lipid bilayer. We attempted to elucidate the molecular mechanism of the early stage of dimerization of these two peptides through extensive replica exchange molecular dynamics simulations. Conformations consisting of various degrees of β-sheets structures, both intra-chain and inter-chain, were found in the simulations. The conformations of the aggregated complex are very diverse, which suggests that the cross-species fibrils formed between the two proteins are highly polymorphic. The driving forces are mainly hydrophobic interactions, including aromatic-aliphatic interactions. The palindromic region of PrP106-126 and SNNFGAIL region of IAPP were found to play important roles in the interaction. Our study sheds insight into the exciting research of protein cross-fibrillation. Proteins 2016; 84:1134-1146. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A program for automatically predicting supramolecular aggregates and its application to urea and porphin [A programme for the automated geometry prediction of supra-molecular aggregates and its application to the examples of urea and porphin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sachse, Torsten; Martinez, Todd J.; Dietzek, Benjamin

Not only the molecular structure but also the presence or absence of aggregates determines many properties of organic materials. Theoretical investigation of such aggregates requires the prediction of a suitable set of diverse structures. Here, we present the open–source program EnergyScan for the unbiased prediction of geometrically diverse sets of small aggregates. Its bottom–up approach is complementary to existing ones by performing a detailed scan of an aggregate's potential energy surface, from which diverse local energy minima are selected. We crossvalidate this approach by predicting both literature–known and heretofore unreported geometries of the urea dimer. We also predict a diversemore » set of dimers of the less intensely studied case of porphin, which we investigate further using quantum chemistry. For several dimers, we find strong deviations from a reference absorption spectrum, which we explain using computed transition densities. Furthermore, this proof of principle clearly shows that EnergyScan successfully predicts aggregates exhibiting large structural and spectral diversity.« less

A hypothetical hierarchical mechanism of the self-assembly of the Escherichia coli RNA polymerase σ(70) subunit.

PubMed

Koroleva, O N; Dubrovin, E V; Tolstova, A P; Kuzmina, N V; Laptinskaya, T V; Yaminsky, I V; Drutsa, V L

2016-02-21

Diverse morphology of aggregates of amyloidogenic proteins has been attracting much attention in the last few years, and there is still no complete understanding of the relationships between various types of aggregates. In this work, we propose the model, which universally explains the formation of morphologically different (wormlike and rodlike) aggregates on the example of a σ(70) subunit of RNA polymerase, which has been recently shown to form amyloid fibrils. Aggregates were studied using AFM in solution and depolarized dynamic light scattering. The obtained results demonstrate comparably low Young's moduli of the wormlike structures (7.8-12.3 MPa) indicating less structured aggregation of monomeric proteins than that typical for β-sheet formation. To shed light on the molecular interaction of the protein during the aggregation, early stages of fibrillization of the σ(70) subunit were modeled using all-atom molecular dynamics. Simulations have shown that the σ(70) subunit is able to form quasi-symmetric extended dimers, which may further interact with each other and grow linearly. The proposed general model explains different pathways of σ(70) subunit aggregation and may be valid for other amyloid proteins.

A program for automatically predicting supramolecular aggregates and its application to urea and porphin [A programme for the automated geometry prediction of supra-molecular aggregates and its application to the examples of urea and porphin

DOE PAGES

Sachse, Torsten; Martinez, Todd J.; Dietzek, Benjamin; ...

2018-01-03

Not only the molecular structure but also the presence or absence of aggregates determines many properties of organic materials. Theoretical investigation of such aggregates requires the prediction of a suitable set of diverse structures. Here, we present the open–source program EnergyScan for the unbiased prediction of geometrically diverse sets of small aggregates. Its bottom–up approach is complementary to existing ones by performing a detailed scan of an aggregate's potential energy surface, from which diverse local energy minima are selected. We crossvalidate this approach by predicting both literature–known and heretofore unreported geometries of the urea dimer. We also predict a diversemore » set of dimers of the less intensely studied case of porphin, which we investigate further using quantum chemistry. For several dimers, we find strong deviations from a reference absorption spectrum, which we explain using computed transition densities. Furthermore, this proof of principle clearly shows that EnergyScan successfully predicts aggregates exhibiting large structural and spectral diversity.« less

Polylogarithmic equilibrium treatment of molecular aggregation and critical concentrations.

PubMed

Michel, Denis; Ruelle, Philippe

2017-02-15

A full equilibrium treatment of molecular aggregation is presented for prototypes of 1D and 3D aggregates, with and without nucleation. By skipping complex kinetic parameters like aggregate size-dependent diffusion, the equilibrium treatment allows us to predict directly time-independent quantities such as critical concentrations. The relationships between the macroscopic equilibrium constants for different paths are first established by statistical corrections and so as to comply with the detailed balance constraints imposed by nucleation, and the composition of the mixture resulting from homogeneous aggregation is then analyzed using a polylogarithmic function. Several critical concentrations are distinguished: the residual monomer concentration at equilibrium (RMC) and the critical nucleation concentration (CNC), which is the threshold concentration of total subunits necessary for initiating aggregation. When increasing the concentration of total subunits, the RMC converges more strongly to its asymptotic value, the equilibrium constant of depolymerization, for 3D aggregates and in the case of nucleation. The CNC moderately depends on the number of subunits in the nucleus, but sharply increases with the difference between the equilibrium constants of polymerization and nucleation. As the RMC and CNC can be numerically but not analytically determined, ansatz equations connecting them to thermodynamic parameters are proposed.

Distinct Spacing Between Anionic Groups: An Essential Chemical Determinant for Achieving Thiophene-Based Ligands to Distinguish β-Amyloid or Tau Polymorphic Aggregates.

PubMed

Klingstedt, Therése; Shirani, Hamid; Mahler, Jasmin; Wegenast-Braun, Bettina M; Nyström, Sofie; Goedert, Michel; Jucker, Mathias; Nilsson, K Peter R

2015-06-15

The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the existence of distinct aggregated morphotypes has been suggested to explain the heterogeneous phenotype reported for these diseases. Thus, the development of molecular probes able to distinguish such morphotypes is essential. We report an anionic tetrameric oligothiophene compound that can be utilized for spectral assignment of different morphotypes of β-amyloid or tau aggregates present in transgenic mice at distinct ages. The ability of the ligand to spectrally distinguish between the aggregated morphotypes was reduced when the spacing between the anionic substituents along the conjugated thiophene backbone was altered, which verified that specific molecular interactions between the ligand and the protein aggregate are necessary to detect aggregate polymorphism. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between different morphotypes of protein aggregates. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Novel dimer based descriptors with solvational computation for QSAR study of oxadiazoylbenzoyl-ureas as novel insect-growth regulators.

PubMed

Fan, Feng; Cheng, Jiagao; Li, Zhong; Xu, Xiaoyong; Qian, Xuhong

2010-02-01

Molecular aggregation state of bioactive compounds plays a key role in its bio-interactive procedure. In this article, based on the structure information of dimers, the simplest model of molecular aggregation state, and combined with solvational computation, total four descriptors (DeltaV, MR2, DeltaE(1), and DeltaE(2)) were calculated for QSAR study of a novel insect-growth regulator, N-(5-phenyl-1,3,4-oxadiazol-2-yl)-N'-benzoyl urea. Two QSAR models were constructed with r(2) = 0.671, q(2) = 0.516 and r(2) = 0.816, q(2) = 0.695, respectively. It implicates that the bioactivity may strongly depend on the characters of molecular aggregation state, especially on the dimeric transport ability from oil phase to water phase. Copyright 2009 Wiley Periodicals, Inc.

Monte Carlo and mean-field studies of phase evolution in concentrated surfactant solutions

NASA Astrophysics Data System (ADS)

Bohbot, Yardena; Ben-Shaul, Avinoam; Granek, Rony; Gelbart, William M.

1995-11-01

A two-dimensional lattice model, originally introduced by Granek et al. [J. Chem. Phys. 101, 4331 (1994)], is used to demonstrate the intricate coupling between the intramicellar interactions that determine the optimal aggregation geometry of surfactant molecules in dilute solution, and the intermicellar interactions that govern the phase behavior at higher concentrations. Three very different scenarios of self-assembly and phase evolution are analyzed in detail, based on Monte Carlo studies and theoretical interpretations involving mean-field, Landau-Ginzburg, Bethe-Peierls, and virial expansion schemes. The basic particles in the model are ``unit micelles'' which, due to spontaneous self-assembly or because of excluded area interactions, can fuse to form larger aggregates. These aggregates are envisaged as flat micelles composed of a bilayerlike body surrounded by a curved semitoroidal rim. The system's Hamiltonian involves one- through four-body potentials between the unit micelles, which account for their tendency to form aggregates of different shapes, e.g., elongated vs disklike micelles. Equivalently, the configurational energy of the system is a sum of micellar self-energies involving the packing free energies of the constituent molecules in the bilayer body and in rim segments of different local curvature. The rim energy is a sum of a line tension term and a 1D curvature energy which depends on the rim spontaneous curvature and bending rigidity. Different combinations of these molecular parameters imply different optimal packing geometries and hence different self-assembly and phase behaviors. The emphasis in this paper is on systems of ``curvature loving'' amphiphiles which, in our model, are characterized by negative line tension. The three systems studied are: (i) A dilute solution of stable disklike micelles which, upon increasing the concentration, undergoes a first-order phase transition to a continuous bilayer with isolated hole defects. An intermediate modulated ``checkerboard'' phase appears under certain conditions at low temperatures. (ii) A system of unit micelles which in dilute solution tend to associate into linear micelles. These micelles are rodlike at low temperatures, becoming increasingly more flexible as the temperature increases. Upon increasing the concentration the micelles grow and undergo (in 2D) a continuous transition into nematic and ``stripe'' phases of long rods. At still higher concentrations the micellar stripes fuse into continuous sheets with line defects. (iii) A system in which, already in dilute solution, the micelles favor the formation of branched aggregates, analogous to the branched cylindrical micelles recently observed in certain surfactant solutions. As the concentration increases the micelles associate into networks (``gels'') composed of a mesh of linear micelles linked by ``T-like'' intermicellar junctions. The network may span the entire system or phase separate and coexist with a dilute micellar phase, depending on the details of the molecular packing parameters.

Protein Quality Control by Molecular Chaperones in Neurodegeneration

PubMed Central

Ciechanover, Aaron; Kwon, Yong Tae

2017-01-01

Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age. Failure in PQC is often associated with neurodegenerative diseases, such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), and prion disease. In fact, many neurodegenerative diseases are considered to be protein misfolding disorders. To prevent the accumulation of disease-causing aggregates, neurons utilize a repertoire of chaperones that recognize misfolded proteins through exposed hydrophobic surfaces and assist their refolding. If such an effort fails, chaperones can facilitate the degradation of terminally misfolded proteins through either the ubiquitin (Ub)-proteasome system (UPS) or the autophagy-lysosome system (hereafter autophagy). If soluble, the substrates associated with chaperones, such as Hsp70, are ubiquitinated by Ub ligases and degraded through the proteasome complex. Some misfolded proteins carrying the KFERQ motif are recognized by the chaperone Hsc70 and delivered to the lysosomal lumen through a process called, chaperone-mediated autophagy (CMA). Aggregation-prone misfolded proteins that remain unprocessed are directed to macroautophagy in which cargoes are collected by adaptors, such as p62/SQSTM-1/Sequestosome-1, and delivered to the autophagosome for lysosomal degradation. The aggregates that have survived all these refolding/degradative processes can still be directly dissolved, i.e., disaggregated by chaperones. Studies have shown that molecular chaperones alleviate the pathogenic symptoms by neurodegeneration-causing protein aggregates. Chaperone-inducing drugs and anti-aggregation drugs are actively exploited for beneficial effects on symptoms of disease. Here, we discuss how chaperones protect misfolded proteins from aggregation and mediate the degradation of terminally misfolded proteins in collaboration with cellular degradative machinery. The topics also include therapeutic approaches to improve the expression and turnover of molecular chaperones and to develop anti-aggregation drugs. PMID:28428740

Ion aggregation in high salt solutions. VII. The effect of cations on the structures of ion aggregates and water hydrogen-bonding network

NASA Astrophysics Data System (ADS)

Choi, Jun-Ho; Choi, Hyung Ran; Jeon, Jonggu; Cho, Minhaeng

2017-10-01

Ions in high salt solutions have a strong propensity to form polydisperse ion aggregates with broad size and shape distributions. In a series of previous comparative investigations using femtosecond IR pump-probe spectroscopy, molecular dynamics simulation, and graph theoretical analysis, we have shown that there exists a morphological difference in the structures of ion aggregates formed in various salt solutions. As salt concentration increases, the ions in high salt solutions form either cluster-like structures excluding water molecules or network-like structures entwined with water hydrogen-bonding networks. Interestingly, such morphological characteristics of the ion aggregates have been found to be in correlation with the solubility limits of salts. An important question that still remains unexplored is why certain salts with different cations have notably different solubility limits in water. Here, carrying out a series of molecular dynamics simulations of aqueous salt solutions and analyzing the distributions and connectivity patterns of ion aggregates with a spectral graph analysis method, we establish the relationship between the salt solubility and the ion aggregate morphology with a special emphasis on the cationic effects on water structures and ion aggregation. We anticipate that the understanding of large scale ion aggregate structures revealed in this study will be critical for elucidating the specific ion effects on the solubility and conformational stability of co-solute molecules such as proteins in water.

Interfacial Properties of NTAIL, an Intrinsically Disordered Protein.

PubMed

Bénarouche, Anaïs; Habchi, Johnny; Cagna, Alain; Maniti, Ofelia; Girard-Egrot, Agnès; Cavalier, Jean-François; Longhi, Sonia; Carrière, Frédéric

2017-12-19

Intrinsically disordered proteins (IDPs) lack stable secondary and tertiary structure under physiological conditions in the absence of their biological partners and thus exist as dynamic ensembles of interconverting conformers, often highly soluble in water. However, in some cases, IDPs such as the ones involved in neurodegenerative diseases can form protein aggregates and their aggregation process may be triggered by the interaction with membranes. Although the interfacial behavior of globular proteins has been extensively studied, experimental data on IDPs at the air/water (A/W) and water/lipid interfaces are scarce. We studied here the intrinsically disordered C-terminal domain of the Hendra virus nucleoprotein (N TAIL ) and compared its interfacial properties to those of lysozyme that is taken as a model globular protein of similar molecular mass. Adsorption of N TAIL at the A/W interface was studied in the absence and presence of phospholipids using Langmuir films, polarization modulated-infrared reflection-absorption spectroscopy, and an automated drop tensiometer for interfacial tension and elastic modulus determination with oscillating bubbles. N TAIL showed a significant surface activity, with a higher adsorption capacity at the A/W interface and penetration into egg phosphatidylcholine monolayer compared to lysozyme. Whereas lysozyme remains folded upon compression of the protein layer at the A/W interface and shows a quasi-pure elastic behavior, N TAIL shows a much higher molecular area and forms a highly viscoelastic film with a high dilational modulus. To our knowledge, a new disorder-to-order transition is thus observed for the N TAIL protein that folds into an antiparallel β-sheet at the A/W interface and presents strong intermolecular interactions. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Molecular mechanisms of protein aggregation from global fitting of kinetic models.

PubMed

Meisl, Georg; Kirkegaard, Julius B; Arosio, Paolo; Michaels, Thomas C T; Vendruscolo, Michele; Dobson, Christopher M; Linse, Sara; Knowles, Tuomas P J

2016-02-01

The elucidation of the molecular mechanisms by which soluble proteins convert into their amyloid forms is a fundamental prerequisite for understanding and controlling disorders that are linked to protein aggregation, such as Alzheimer's and Parkinson's diseases. However, because of the complexity associated with aggregation reaction networks, the analysis of kinetic data of protein aggregation to obtain the underlying mechanisms represents a complex task. Here we describe a framework, using quantitative kinetic assays and global fitting, to determine and to verify a molecular mechanism for aggregation reactions that is compatible with experimental kinetic data. We implement this approach in a web-based software, AmyloFit. Our procedure starts from the results of kinetic experiments that measure the concentration of aggregate mass as a function of time. We illustrate the approach with results from the aggregation of the β-amyloid (Aβ) peptides measured using thioflavin T, but the method is suitable for data from any similar kinetic experiment measuring the accumulation of aggregate mass as a function of time; the input data are in the form of a tab-separated text file. We also outline general experimental strategies and practical considerations for obtaining kinetic data of sufficient quality to draw detailed mechanistic conclusions, and the procedure starts with instructions for extensive data quality control. For the core part of the analysis, we provide an online platform (http://www.amylofit.ch.cam.ac.uk) that enables robust global analysis of kinetic data without the need for extensive programming or detailed mathematical knowledge. The software automates repetitive tasks and guides users through the key steps of kinetic analysis: determination of constraints to be placed on the aggregation mechanism based on the concentration dependence of the aggregation reaction, choosing from several fundamental models describing assembly into linear aggregates and fitting the chosen models using an advanced minimization algorithm to yield the reaction orders and rate constants. Finally, we outline how to use this approach to investigate which targets potential inhibitors of amyloid formation bind to and where in the reaction mechanism they act. The protocol, from processing data to determining mechanisms, can be completed in <1 d.

Specific binding of large aggregates of amphiphilic molecules to the respective antibodies.

PubMed

Nabok, Alexei; Tsargorodskaya, Anna; Holloway, Alan; Starodub, Nikolay F; Demchenko, Anna

2007-07-31

The Binding of nonylphenol to respective antibodies immobilized on solid substrates was studied with the methods of total internal reflection ellipsometry (TIRE) and QCM (quartz crystal microbalance) impedance spectroscopy. The binding reaction was proved to be highly specific having an association constant of KA=1.6x10(6) mol(-1) L and resulted in an increase in both the adsorbed layer thickness of 23 nm and the added mass of 18.3 microg/cm2 at saturation. The obtained responses of both TIRE and QCM methods are substantially higher than anticipated for the immune binding of single molecules of nonylphenol. The mechanism of binding of large aggregates of nonylphenol was suggested instead. Modeling of the micelle of amphiphilic nonylphenol molecules in aqueous solutions yielded a micelle size of about 38 nm. The mechanism of binding of large molecular aggregates to respective antibodies can be extended to other hydrophobic low-molecular-weight toxins such as T-2 mycotoxin. The formation of large molecular aggregates of nonylphenol and T-2 mycotoxin molecules on the surface was proved by the AFM study.

Characterization of reaction intermediate aggregates in aniline oxidative polymerization at low proton concentration.

PubMed

Ding, Zhongfen; Sanchez, Timothy; Labouriau, Andrea; Iyer, Srinivas; Larson, Toti; Currier, Robert; Zhao, Yusheng; Yang, Dali

2010-08-19

Aggregates of reaction intermediates form during the early stages of aniline oxidative polymerization whenever the initial mole ratio of proton concentration to aniline monomer concentration is low ([H(+)](0)/[An](0)

Preparation of non-aggregating aqueous fullerenes in highly saline solutions with a biocompatible non-ionic polymer

NASA Astrophysics Data System (ADS)

Aich, Nirupam; Boateng, Linkel K.; Flora, Joseph R. V.; Saleh, Navid B.

2013-10-01

Size-tunable stable aqueous fullerenes were prepared with different concentrations of biocompatible block-copolymer pluronic (PA) F-127, ranging from 0.001% to 1% (w/v). Size uniformity increased with the increase in PA concentration, yielding optimum 58.8 ± 5.6 and 61.8 ± 5.6 nm nC60s and nC70s, respectively (0.10%w/v PA), as observed using a dynamic light scattering technique. Fullerene aqueous suspensions also manifested enhanced stability in saline solution, Dulbecco’s modified Eagle medium (DMEM), and Roswell Park Memorial Institute (RPMI) culture medium. Transmission electron microscopy was performed to elaborate on the morphology and size specificity of fullerene clusters. Physicochemical characterizations of the suspended fullerenes were performed through UV-vis spectroscopy and electrophoretic mobility measurements. PA molecules showed size restriction by encasement, as observed via molecular dynamics simulations. Such solubilization with controllable size and non-aggregating behavior can facilitate application enhancement and mechanistic environmental and toxicological studies of size-specific fullerenes.

Self-association of urea in aqueous solutions: a Voronoi polyhedron analysis study.

PubMed

Idrissi, Abdenacer; Damay, Pierre; Yukichi, Kitamura; Jedlovszky, Pal

2008-10-28

Molecular dynamics simulation of the aqueous solutions of urea of seven different concentrations (including neat water as a reference system) has been performed on the isothermal-isobaric (N,p,T) ensemble. The ability of the urea molecules of self-association is investigated by means of the method of Voronoi polyhedra. For this purpose, all the analyses are repeated by removing one of the two components from the sample configurations and considering only the other one. In this way, the analysis of self-aggregation is reduced to the analysis of voids, a problem that can routinely be addressed by means of Voronoi analysis. The obtained results show that the urea molecules exhibit self-association behavior, which is found to be the strongest at the urea mole fraction of 0.23. However, the size of these urea aggregates is found to be rather limited; on average, they are built up by 3-4 molecules, and never exceed the size of 20-25 molecules.

Analysis of Unbound Aggregate Layer Deformation Behavior from Full Scale Aircraft Gear Loading with Wander

ERIC Educational Resources Information Center

Donovan, Phillip Raymond

2009-01-01

This study focuses on the analysis of the behavior of unbound aggregates to offset wheel loads. Test data from full-scale aircraft gear loading conducted at the National Airport Pavement Test Facility (NAPTF) by the Federal Aviation Administration (FAA) are used to investigate the effects of wander (offset loads) on the deformation behavior of…

A model for bacterial colonization of sinking aggregates.

PubMed

Bearon, R N

2007-01-01

Sinking aggregates provide important nutrient-rich environments for marine bacteria. Quantifying the rate at which motile bacteria colonize such aggregations is important in understanding the microbial loop in the pelagic food web. In this paper, a simple analytical model is presented to predict the rate at which bacteria undergoing a random walk encounter a sinking aggregate. The model incorporates the flow field generated by the sinking aggregate, the swimming behavior of the bacteria, and the interaction of the flow with the swimming behavior. An expression for the encounter rate is computed in the limit of large Péclet number when the random walk can be approximated by a diffusion process. Comparison with an individual-based numerical simulation is also given.

A Putative Biochemical Engram of Long-term Memory

PubMed Central

Li, Liying; Sanchez, Consuelo Perez; Slaughter, Brian D.; Zhao, Yubai; Khan, Mohammed Repon; Unruh, Jay R.; Rubinstein, Boris; Si, Kausik

2016-01-01

Summary How a transient experience creates an enduring yet dynamic memory remains an unresolved issue in studies of memory. Experience-dependent aggregation of the RNA-binding protein CPEB/Orb2 is one of the candidate mechanisms of memory maintenance. Here, using tools that allow rapid and reversible inactivation of Orb2 protein in neurons we find that Orb2 activity is required for encoding and recall of memory. From a screen we have identified a DNA-J family chaperone, JJJ2, which facilitates Orb2 aggregation, and ectopic expression of JJJ2 enhances the animal’s capacity to form long-term memory. Finally, we have developed tools to visualize training-dependent aggregation of Orb2. We find that aggregated Orb2 in a subset of mushroom body neurons can serve as a “molecular signature” of memory and predict memory strength. Our data indicates that self-sustaining aggregates of Orb2 may serve as a physical substrate of memory and provide a molecular basis for the perduring yet malleable nature of memory. PMID:27818176

Stepwise Nucleation of Aniline: Emergence of Spectroscopic Fingerprints of the Liquid Phase.

PubMed

Leon, Iker; Usabiaga, Imanol; Arnaiz, Pedro Felipe; Lesarri, Alberto; Fernández, Jose Andres

2018-06-11

We deal here with the controlled nucleation of aniline from the isolated molecule until formation of a moderately large aggregate: aniline nonamer. The structure of the cluster at each step of the nucleation was unravelled combining mass-resolved IR spectroscopy and computational chemistry, demonstrating that aggregation is primarily guided by formation of extensive N-H···N hydrogen bond networks that give the aggregates a sort of branched backbone, in clear competition with multiple N-H/C-H···pi and pi···pi interactions. The result is the co-existence of close nucleation paths connecting relational aggregates. The delicate balance of molecular forces makes the aniline clusters a challenge for molecular orbital calculations and an ideal system to refine the present nucleation models. Noticeably, spectroscopic signatures characteristic of the condensed phase are apparent in the nanometer-size aggregates formed in this work. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels With In Vivo Results.

PubMed

Wang, Shiying; Wang, Claudia Y; Unnikrishnan, Sunil; Klibanov, Alexander L; Hossack, John A; Mauldin, F William

2015-11-01

The objective of this study was to optically verify the dynamic behaviors of adherent microbubbles in large blood vessel environments in response to a new ultrasound technique using modulated acoustic radiation force. Polydimethylsiloxane (PDMS) flow channels coated with streptavidin were used in targeted groups to mimic large blood vessels. The custom-modulated acoustic radiation force beam sequence was programmed on a Verasonics research scanner. In vitro experiments were performed by injecting a biotinylated lipid-perfluorobutane microbubble dispersion through flow channels. The dynamic response of adherent microbubbles was detected acoustically and simultaneously visualized using a video camera connected to a microscope. In vivo verification was performed in a large abdominal blood vessel of a murine model for inflammation with injection of biotinylated microbubbles conjugated with P-selectin antibody. Aggregates of adherent microbubbles were observed optically under the influence of acoustic radiation force. Large microbubble aggregates were observed solely in control groups without targeted adhesion. Additionally, the dispersion of microbubble aggregates were demonstrated to lead to a transient acoustic signal enhancement in control groups (a new phenomenon we refer to as "control peak"). In agreement with in vitro results, the control peak phenomenon was observed in vivo in a murine model. This study provides the first optical observation of microbubble-binding dynamics in large blood vessel environments with application of a modulated acoustic radiation force beam sequence. With targeted adhesion, secondary radiation forces were unable to produce large aggregates of adherent microbubbles. Additionally, the new phenomenon called control peak was observed both in vitro and in vivo in a murine model for the first time. The findings in this study provide us with a better understanding of microbubble behaviors in large blood vessel environments with application of acoustic radiation force and could potentially guide future beam sequence designs or signal processing routines for enhanced ultrasound molecular imaging.

Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels with In Vivo Results

PubMed Central

Wang, Shiying; Wang, Claudia Y.; Unnikrishnan, Sunil; Klibanov, Alexander L.; Hossack, John A.; Mauldin, F. William

2015-01-01

Objectives To optically verify the dynamic behaviors of adherent microbubbles in large blood vessel environments in response to a new ultrasound technique using modulated acoustic radiation force. Materials and Methods Polydimethylsiloxane (PDMS) flow channels coated with streptavidin were used in targeted groups to mimic large blood vessels. The custom modulated acoustic radiation force beam sequence was programmed on a Verasonics research scanner. In vitro experiments were performed by injecting a biotinylated lipid-perfluorobutane microbubble dispersion through flow channels. The dynamic response of adherent microbubbles was detected acoustically and simultaneously visualized using a video camera connected to a microscope. In vivo verification was performed in a large abdominal blood vessel of a murine model for inflammation with injection of biotinylated microbubbles conjugated with P-selectin antibody. Results Aggregates of adherent microbubbles were observed optically under the influence of acoustic radiation force. Large microbubble aggregates were observed solely in control groups without targeted adhesion. Additionally, the dispersion of microbubble aggregates were demonstrated to lead to a transient acoustic signal enhancement in control groups (a new phenomenon we refer to as “control peak”). In agreement with in vitro results, the “control peak” phenomenon was observed in vivo in a murine model. Conclusions This study provides the first optical observation of microbubble binding dynamics in large blood vessel environments with application of a modulated acoustic radiation force beam sequence. With targeted adhesion, secondary radiation forces were unable to produce large aggregates of adherent microbubbles. Additionally, the new phenomenon called “control peak” was observed both in vitro and in vivo in a murine model for the first time. The findings in this study provide us with a better understanding of microbubble behaviors in large blood vessel environments with application of acoustic radiation force, and could potentially guide future beam sequence designs or signal processing routines for enhanced ultrasound molecular imaging. PMID:26135018

Identification of Esters as Novel Aggregation Pheromone Components Produced by the Male Powder-Post Beetle, Lyctus africanus Lesne (Coleoptera: Lyctinae).

PubMed

Kartika, Titik; Shimizu, Nobuhiro; Yoshimura, Tsuyoshi

2015-01-01

Lyctus africanus is a cosmopolitan powder-post beetle that is considered one of the major pests threatening timber and timber products. Because infestations of this beetle are inconspicuous, damage is difficult to detect and identification is often delayed. We identified the chemical compounds involved in the aggregation behavior of L. africanus using preparations of crude hexanic extracts from male and female beetles (ME and FE, respectively). Both male and female beetles showed significant preferences for ME, which was found to contain three esters. FE was ignored by both the sexes. Further bioassay confirmed the role of esters in the aggregation behavior of L. africanus. Three esters were identified as 2-propyl dodecanoate, 3-pentyl dodecanoate, and 3-pentyl tetradecanoate. Further behavioral bioassays revealed 3-pentyl dodecanoate to play the main role in the aggregation behavior of female L. africanus beetles. However, significantly more beetles aggregated on a paper disk treated with a blend of the three esters than on a paper disk treated with a single ester. This is the first report on pheromone identification in L. africanus; in addition, the study for the first time presents 3-pentyl dodecanoate as an insect pheromone.

Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease.

PubMed

Duan, Songwei; Guan, Xiaoyin; Lin, Runxuan; Liu, Xincheng; Yan, Ying; Lin, Ruibang; Zhang, Tianqi; Chen, Xueman; Huang, Jiaqi; Sun, Xicui; Li, Qingqing; Fang, Shaoliang; Xu, Jun; Yao, Zhibin; Gu, Huaiyu

2015-05-01

Alzheimer's disease (AD) is characterized by amyloid β (Aβ) peptide aggregation and cholinergic neurodegeneration. Therefore, in this paper, we examined silibinin, a flavonoid extracted from Silybum marianum, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for AD treatment. To achieve this, we used molecular docking and molecular dynamics simulations to examine the affinity of silibinin with Aβ and AChE in silico. Next, we used circular dichroism and transmission electron microscopy to study the anti-Aβ aggregation capability of silibinin in vitro. Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay, immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun experiment were performed on silibinin-treated APP/PS1 transgenic mice. In molecular dynamics simulations, silibinin interacted with Aβ and AChE to form different stable complexes. After the administration of silibinin, AChE activity and Aβ aggregations were down-regulated, and the quantity of AChE also decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater scores in the Morris Water Maze. Moreover, silibinin could increase the number of newly generated microglia, astrocytes, neurons, and neuronal precursor cells. Taken together, these data suggest that silibinin could act as a dual inhibitor of AChE and Aβ peptide aggregation, therefore suggesting a therapeutic strategy for AD treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO 4 or NaH 2PO 4: Evidence for its Molecular Origin.

PubMed

Weng, Lindong; Elliott, Gloria D

2015-07-01

The present study is aimed at understanding how the interactions between sugar molecules and phosphate ions affect the glass transition temperature of their mixtures, and the implications for pharmaceutical formulations. The glass transition temperature (Tg) and the α-relaxation temperature (Tα) of dehydrated trehalose/sodium phosphate mixtures (monobasic or dibasic) were determined by differential scanning calorimetry and dynamic mechanical analysis, respectively. Molecular dynamics simulations were also conducted to investigate the microscopic interactions between sugar molecules and phosphate ions. The hydrogen-bonding characteristics and the self-aggregation features of these mixtures were quantified and compared. Thermal analysis measurements demonstrated that the addition of NaH2PO4 decreased both the glass transition temperature and the α-relaxation temperature of the dehydrated trehalose/NaH2PO4 mixture compared to trehalose alone while both Tg and Tα were increased by adding Na2HPO4 to pure trehalose. The hydrogen-bonding interactions between trehalose and HPO4(2-) were found to be stronger than both the trehalose-trehalose hydrogen bonds and those formed between trehalose and H2PO4(-). The HPO4(2-) ions also aggregated into smaller clusters than H2PO4(-) ions. The trehalose/Na2HPO4 mixture yielded a higher T g than pure trehalose because marginally self-aggregated HPO4(2-) ions established a strengthened hydrogen-bonding network with trehalose molecules. In contrast H2PO4(-) ions served only as plasticizers, resulting in a lower Tg of the mixtures than trehalose alone, creating large-sized ionic pockets, weakening interactions, and disrupting the original hydrogen-bonding network amongst trehalose molecules.

Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO4 or NaH2PO4: Evidence for its Molecular Origin

PubMed Central

Weng, Lindong; Elliott, Gloria D.

2015-01-01

Purpose The present study is aimed at understanding how the interactions between sugar molecules and phosphate ions affect the glass transition temperature of their mixtures, and the implications for pharmaceutical formulations. Methods The glass transition temperature (Tg) and the α-relaxation temperature (Tα) of dehydrated trehalose/sodium phosphate mixtures (monobasic or dibasic) were determined by differential scanning calorimetry and dynamic mechanical analysis, respectively. Molecular dynamics simulations were also conducted to investigate the microscopic interactions between sugar molecules and phosphate ions. The hydrogen-bonding characteristics and the self-aggregation features of these mixtures were quantified and compared. Results Thermal analysis measurements demonstrated that the addition of NaH2PO4 decreased both the glass transition temperature and the α-relaxation temperature of the dehydrated trehalose/NaH2PO4 mixture compared to trehalose alone while both Tg and Tα were increased by adding Na2HPO4 to pure trehalose. The hydrogen-bonding interactions between trehalose and HPO42− were found to be stronger than both the trehalose-trehalose hydrogen bonds and those formed between trehalose and H2PO4−. The HPO42− ions also aggregated into smaller clusters than H2PO4− ions. Conclusions The trehalose/Na2HPO4 mixture yielded a higher Tg than pure trehalose because marginally self-aggregated HPO42− ions established a strengthened hydrogen-bonding network with trehalose molecules. In contrast H2PO4− ions served only as plasticizers, resulting in a lower Tg of the mixtures than trehalose alone, creating large-sized ionic pockets, weakening interactions, and disrupting the original hydrogen-bonding network amongst trehalose molecules. PMID:25537342

Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans

PubMed Central

Bendesky, Andres; Pitts, Jason; Rockman, Matthew V.; Chen, William C.; Tan, Man-Wah; Kruglyak, Leonid; Bargmann, Cornelia I.

2012-01-01

Aggregation is a social behavior that varies between and within species, providing a model to study the genetic basis of behavioral diversity. In the nematode Caenorhabditis elegans, aggregation is regulated by environmental context and by two neuromodulatory pathways, one dependent on the neuropeptide receptor NPR-1 and one dependent on the TGF-β family protein DAF-7. To gain further insight into the genetic regulation of aggregation, we characterize natural variation underlying behavioral differences between two wild-type C. elegans strains, N2 and CB4856. Using quantitative genetic techniques, including a survey of chromosome substitution strains and QTL analysis of recombinant inbred lines, we identify three new QTLs affecting aggregation in addition to the two known N2 mutations in npr-1 and glb-5. Fine-mapping with near-isogenic lines localized one QTL, accounting for 5%–8% of the behavioral variance between N2 and CB4856, 3′ to the transcript of the GABA neurotransmitter receptor gene exp-1. Quantitative complementation tests demonstrated that this QTL affects exp-1, identifying exp-1 and GABA signaling as new regulators of aggregation. exp-1 interacts genetically with the daf-7 TGF-β pathway, which integrates food availability and population density, and exp-1 mutations affect the level of daf-7 expression. Our results add to growing evidence that genetic variation affecting neurotransmitter receptor genes is a source of natural behavioral variation. PMID:23284308

Differential Interaction of Antimicrobial Peptides with Lipid Structures Studied by Coarse-Grained Molecular Dynamics Simulations.

PubMed

Balatti, Galo E; Ambroggio, Ernesto E; Fidelio, Gerardo D; Martini, M Florencia; Pickholz, Mónica

2017-10-20

In this work; we investigated the differential interaction of amphiphilic antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid structures by means of extensive molecular dynamics simulations. By using a coarse-grained (CG) model within the MARTINI force field; we simulated the peptide-lipid system from three different initial configurations: (a) peptides in water in the presence of a pre-equilibrated lipid bilayer; (b) peptides inside the hydrophobic core of the membrane; and (c) random configurations that allow self-assembled molecular structures. This last approach allowed us to sample the structural space of the systems and consider cooperative effects. The peptides used in our simulations are aurein 1.2 and maculatin 1.1; two well-known antimicrobial peptides from the Australian tree frogs; and molecules that present different membrane-perturbing behaviors. Our results showed differential behaviors for each type of peptide seen in a different organization that could guide a molecular interpretation of the experimental data. While both peptides are capable of forming membrane aggregates; the aurein 1.2 ones have a pore-like structure and exhibit a higher level of organization than those conformed by maculatin 1.1. Furthermore; maculatin 1.1 has a strong tendency to form clusters and induce curvature at low peptide-lipid ratios. The exploration of the possible lipid-peptide structures; as the one carried out here; could be a good tool for recognizing specific configurations that should be further studied with more sophisticated methodologies.

Molecular Dynamics Simulations to Clarify the Concentration Dependency of Protein Aggregation

NASA Astrophysics Data System (ADS)

Nishikawa, Naohiro; Sakae, Yoshitake; Okamoto, Yuko

We examined the concentration dependency of amyloid protein aggregation by using several molecular dynamics simulations, which were performed with different concentrations for each system. For these simulations, we used a fragment of amyloid-β, which is believed to be the cause of Alzheimer's disease, as our simulation system. We found that high concentration of amyloid peptides promotes the formation of β-structures which is the origin of amyloid fibrils.

Assessing the effect of D59P mutation in the DE loop region in amyloid aggregation propensity of β2-microglobulin: A molecular dynamics simulation study.

PubMed

Narang, Simranjeet S; Shuaib, Suniba; Goyal, Deepti; Goyal, Bhupesh

2018-01-01

Dialysis-related amyloidosis (DRA) is a severe condition characterized by the accumulation of amyloidogenic β2-microglobulin (β2m) protein around skeletal joints and bones. The recent studies highlighted a critical role of the DE loop region for β2m stability and amyloid aggregation propensity. Despite significant efforts, the molecular mechanism of enhanced aggregation due to D59P mutation in the DE loop region remain elusive. In the present study, explicit-solvent molecular dynamics (MD) simulations were performed to examine the key changes in the structural and dynamic properties of wild type (wt) β2m upon D59P mutation. MD simulations reveal a decrease in the average number of hydrogen bonds in the loop regions on D59P mutation that enhances conformational flexibility, which lead to higher aggregation propensity of D59P as compare to wt β2m. The principal component analysis (PCA) highlight that D59P covers a larger region of phase space and display a higher trace value than wt β2m, which suggest an overall enhancement in the conformational flexibility. D59P display two minimum energy basins in the free energy landscape (FEL) that are associated with thermodynamically less stable conformational states as compare to single minimum energy basin in wt β2m. The present study provides theoretical insights into the molecular mechanism behind the higher aggregation propensity of D59P as compare to wt β2m. © 2017 Wiley Periodicals, Inc.

Aggregation in concentrated protein solutions: Insights from rheology, neutron scattering and molecular simulations

NASA Astrophysics Data System (ADS)

Castellanos, Maria Monica

Aggregation of therapeutic proteins is currently one of the major challenges in the bio-pharmaceutical industry, because aggregates could induce immunogenic responses and compromise the quality of the product. Current scientific efforts, both in industry and academia, are focused on developing rational approaches to screen different drug candidates and predict their stability under different conditions. Moreover, aggregation is promoted in highly concentrated protein solutions, which are typically required for subcutaneous injection. In order to gain further understanding about the mechanisms that lead to aggregation, an approach that combined rheology, neutron scattering, and molecular simulations was undertaken. Two model systems were studied in this work: Bovine Serum Albumin in surfactant-free Phosphate Buffered Saline at pH = 7.4 at concentrations from 11 mg/mL up to ˜519 mg/mL, and a monoclonal antibody in 20 mM Histidine/Histidine Hydrochloride at pH = 6.0 with 60 mg/mL trehalose and 0.2 mg/mL polysorbate-80 at concentrations from 53 mg/mL up to ˜220 mg/mL. The antibody used here has three mutations in the CH2 domain, which result in lower stability upon incubation at 40 °C with respect to the wild-type protein, based on size-exclusion chromatography assays. This temperature is below 49 °C, where unfolding of the least stable, CH2 domain occurs, according to differential scanning calorimetry. This dissertation focuses on identifying the role of aggregation on the viscosity of protein solutions. The protein solutions of this work show an increase in the low shear viscosity in the absence of surfactants, because proteins adsorb at the air/water interface forming a viscoelastic film that affects the measured rheology. Stable surfactant-laden protein solutions behave as simple Newtonian fluids. However, the surfactant-laden antibody solution also shows an increase in the low shear viscosity from bulk aggregation, after prolonged incubation at 40 °C. Small-angle neutron scattering experiments were used to characterize the antibody aggregates responsible for this non-Newtonian response. From the neutron scattering data, a weak barrier leading to reversible aggregation is identified. Therefore, proteins aggregate weakly after colliding hydrodynamically, unless they find a favorable contact with high binding energy. Two types of antibody aggregates were identified: oligomers with average radius of gyration of ˜10 nm, and fractal aggregates larger than ˜ 0.1 microm formed by a reaction-limited aggregation process. A characteristic upturn in the scattered intensity at low wavevector and a low shear viscosity increase are observed in aggregated protein solutions. These features are removed by filtering with a 0.2 microm filter, which also eliminates the submicron fractal aggregates. Biophysical characterization supports the conclusions from the rheology and neutron scattering experiments. Finally, molecular dynamics simulations were used to understand the effects of disulfide bonds on the conformational stability of serum albumin. Changes in disulfide bonds in the native structure could lead to partial unfolding, and the formation of aggregates through inter-molecular disulfide bonds. Therefore, it is important to understand the role of each disulfide bond on the structure and dynamics of the protein. After removing disulfide bonds, changes occur in the dynamic correlations between different residues, and the secondary and tertiary structure of albumin. However, not all disulfide bonds affect the conformation of the protein, suggesting that other interactions are more relevant to keep the stability in certain regions. Removal of all disulfide bonds using molecular dynamics is proposed as a practical prescreening tool to identify disulfide bonds that are important for the conformational stability. As a result, some disulfide bonds can be mutated without affecting the conformation of the protein.

Self-Association Process of a Peptide in Solution: From β-Sheet Filaments to Large Embedded Nanotubes

PubMed Central

Valéry, C.; Artzner, F.; Robert, B.; Gulick, T.; Keller, G.; Grabielle-Madelmont, C.; Torres, M.-L.; Cherif-Cheikh, R.; Paternostre, M.

2004-01-01

Lanreotide is a synthetic octapeptide used in the therapy against acromegaly. When mixed with pure water at 10% (w/w), Lanreotide (acetate salt) forms liquid crystalline and monodisperse nanotubes with a radius of 120 Å. The molecular and supramolecular organization of these structures has been determined in a previous work as relying on the lateral association of 26 β-sheet filaments made of peptide noncovalent dimers, the basic building blocks. The work presented here has been devoted to the corresponding self-association mechanisms, through the characterization of the Lanreotide structures formed in water, as a function of peptide (acetate salt) concentration (from 2% to 70% (w/w)) and temperature (from 15°C to 70°C). The corresponding states of water were also identified and quantified from the thermal behavior of water in the Lanreotide mixtures. At room temperature and below 3% (w/w) Lanreotide acetate in water, soluble aggregates were detected. From 3% to 20% (w/w) long individual and monodisperse nanotubes crystallized in a hexagonal lattice were evidenced. Their molecular and supramolecular organizations are identical to the ones characterized for the 10% (w/w) sample. Heating induces the dissolution of the nanotubes into soluble aggregates of the same structural characteristics as the room temperature ones. The solubilization temperature increases from 20°C to 70°C with the peptide concentration and reaches a plateau between 15% and 25% (w/w) in peptide. These aggregates are proposed to be the β-sheet filaments that self-associate to build the walls of the nanotubes. Above 20% (w/w) of Lanreotide acetate in water, polydisperse embedded nanotubes are formed and the hexagonal lattice is lost. These embedded nanotubes exhibit the same molecular and supramolecular organizations as the individual monodisperse nanotubes formed at lower peptide concentration. The embedded nanotubes do not melt in the range of temperature studied indicating a higher thermodynamic stability than individual nanotubes. In parallel, the thermal behaviors of water in mixtures containing 2–80% (w/w) in peptide have been studied by differential scanning calorimetry, and three different types of water were characterized: 1), bulk water melting at 0°C, 2), nonfreezing water, and 3), interfacial water melting below 0°C. The domains of existence and coexistence of these different water states are related to the different Lanreotide supramolecular structures. All these results were compiled into a binary Lanreotide-water phase diagram and allowed to propose a self-association mechanism of Lanreotide filaments into monodisperse individual nanotubes and embedded nanotubes. PMID:15041685

Aggregation of γ-crystallins associated with human cataracts via domain swapping at the C-terminal β-strands

PubMed Central

Das, Payel; King, Jonathan A.; Zhou, Ruhong

2011-01-01

The prevalent eye disease age-onset cataract is associated with aggregation of human γD-crystallins, one of the longest-lived proteins. Identification of the γ-crystallin precursors to aggregates is crucial for developing strategies to prevent and reverse cataract. Our microseconds of atomistic molecular dynamics simulations uncover the molecular structure of the experimentally detected aggregation-prone folding intermediate species of monomeric native γD-crystallin with a largely folded C-terminal domain and a mostly unfolded N-terminal domain. About 30 residues including a, b, and c strands from the Greek Key motif 4 of the C-terminal domain experience strong solvent exposure of hydrophobic residues as well as partial unstructuring upon N-terminal domain unfolding. Those strands comprise the domain–domain interface crucial for unusually high stability of γD-crystallin. We further simulate the intermolecular linkage of these monomeric aggregation precursors, which reveals domain-swapped dimeric structures. In the simulated dimeric structures, the N-terminal domain of one monomer is frequently found in contact with residues 135–164 encompassing the a, b, and c strands of the Greek Key motif 4 of the second molecule. The present results suggest that γD-crystallin may polymerize through successive domain swapping of those three C-terminal β-strands leading to age-onset cataract, as an evolutionary cost of its very high stability. Alanine substitutions of the hydrophobic residues in those aggregation-prone β-strands, such as L145 and M147, hinder domain swapping as a pathway toward dimerization. These findings thus provide critical molecular insights onto the initial stages of age-onset cataract, which is important for understanding protein aggregation diseases. PMID:21670251

Evaluation of conceptual models of natural organic matter (humus) from a consideration of the chemical and biochemical processes of humification

USGS Publications Warehouse

Wershaw, Robert L.

2004-01-01

Natural organic matter (NOM) has been studied for more than 200 years because of its importance in enhancing soil fertility, soil structure, and water-holding capacity and as a carbon sink in the global carbon cycle. Two different types of models have been proposed for NOM: (1) the humic polymer models and (2) the molecular aggregate models. In the humic polymer models, NOM molecules are depicted as large (humic) polymers that have unique chemical structures that are different from those of the precursor plant degradation products. In the molecular aggregate models, NOM is depicted as being composed of molecular aggregates (supramolecular aggregates) of plant degradation products held together by non-covalent bonds. The preponderance of evidence favors the supramolecular aggregate models. These models were developed by studying the properties of NOM extracted from soils and natural waters, and as such, they provide only a very generalized picture of the structure of NOM aggregates in soils and natural waters prior to extraction. A compartmental model, in which the structure of the NOM in each of the compartments is treated separately, should provide a more accurate representation of NOM in soil and sediment systems. The proposed NOM compartments are: (1) partially degraded plant tissue, (2) biomass from microorganisms, (3) organic coatings on mineral grains, (4) pyrolytic carbon, (5) organic precipitates, and (6) dissolved organic matter (DOM) in interstitial water. Within each of these compartments there are NOM supramolecular aggregates that will be dissolved by the solvent systems that are used by researchers for extraction of NOM from soils and sediments. In natural water systems DOM may be considered as existing in two subcompartments: (1) truly dissolved DOM and (2) colloidal DOM.

Asymmetrical flow field-flow fractionation coupled with multi-angle laser light scattering for stability comparison of virus-like particles in different solution environments.

PubMed

Chen, Yi; Zhang, Yan; Zhou, Yuefang; Luo, Jian; Su, Zhiguo

2016-06-08

The stabilities of two commercially available virus like particles, CHO-HBsAg expressed by Chinese hamster ovary (CHO) cells and Hans-HBsAg expressed by Hansenula polymorpha (Hans), were compared using AF4-MALLS under different treatment processes. The initial molecular weight and hydrodynamic diameter of CHO-HBsAg measured with AF4-MALLS were 4727kDa and 29.4nm, while those of Hans-HBsAg were 3039kDa and 22.8nm respectively. In salt solution of 2M ammonium sulfate, the molecular weight and size of CHO-HBsAg had little change, and its antigenicity remained 95%, while those of Hans-HBsAg changed greatly, resulting in aggregation and 75% antigenicity loss. In freeze-thaw operations, Hans-HBsAg aggregated heavily. Most of the aggregates precipitated and the rest soluble aggregates reached 10(5)-10(6)kDa in molecular weight. The antigenicity of Hans-HBsAg decreased to 26.9% after five freeze-thaw cycles. For CHO-HBsAg, there was no obvious aggregation in freeze-thaw, and the antigenicity retained above 98%. In heating process, Hans-HBsAg gradually aggregated to large particles with temperature and the antigenicity decreased to 10% when the temperature reached 80°C. In contrast, CHO-HBsAg would not aggregate with temperature, remained 92% antigenicity at 80°C. The study demonstrated that CHO-HBsAg appeared to be a superior vaccine antigen in term of particle stability and constant antigenicity, which are important in production, transportation and storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of shear forces on the aggregation and sedimentation behavior of cerium dioxide (CeO2) nanoparticles under different hydrochemical conditions

NASA Astrophysics Data System (ADS)

Lv, Bowen; Wang, Chao; Hou, Jun; Wang, Peifang; Miao, Lingzhan; Li, Yi; Ao, Yanhui; Yang, Yangyang; You, Guoxiang; Xu, Yi

2016-07-01

This study contributed to a better understanding of the behavior of nanoparticles (NPs) in dynamic water. First, the aggregation behavior of CeO2 NPs at different pH values in various salt solutions was examined to determine the appropriate hydrochemical conditions for hydrodynamics study. Second, the aggregation behavior of CeO2 NPs under different shear forces was investigated at pH 4 and ionic strength 0 in various salt solutions to find out whether shear forces could influence the stability of the nanoparticles and if yes, how. Also, five-stage sedimentation tests were conducted to understand the influence of shear stress on the vertical distribution of CeO2 NPs in natural waters. The aggregation test showed that the shear force could increase the collision efficiency between NPs during aggregation and cause a relatively large mass of NPs to remain in suspension. Consequently, the nanoparticles had a greater possibility of continued aggregation. The sedimentation test under static conditions indicated that a large mass of NPs (>1000 nm) sink to the bottom layer, leaving only small aggregates dispersed in the upper or middle layer of the solution. However, later sedimentation studies under stirring conditions demonstrated that shear forces can disrupt this stratification phenomenon. These results suggest that shear forces can influence the spatial distribution of NPs in natural waters, which might lead to different toxicities of CeO2 NPs to aquatic organisms distributed in the different water layers. This study contributes to a better understanding of nanomaterial toxicology and provides a way for further research.

Vocal Fold Mucus Aggregation in Persons with Voice Disorders

ERIC Educational Resources Information Center

Bonilha, Heather Shaw; White, Lisa; Kuckhahn, Kelsey; Gerlach, Terri Treman; Deliyski, Dimitar D.

2012-01-01

Mucus aggregation on the vocal folds is a common finding from laryngeal endoscopy. Patients with voice disorders report the presence of mucus aggregation. Patients also report that mucus aggregation causes them to clear their throat, a behavior believed to be harmful to vocal fold mucosa. Even though clinicians and patients report and discuss…

Insights in understanding aggregate formation and dissociation in cation exchange chromatography for a structurally unstable Fc-fusion protein.

PubMed

Chen, Zhiqiang; Huang, Chao; Chennamsetty, Naresh; Xu, Xuankuo; Li, Zheng Jian

2016-08-19

Cation-exchange chromatography (CEX) of a structurally unstable Fc-fusion protein exhibited multi-peak elution profile upon a salt-step elution due to protein aggregation during intra-column buffer transition where low pH and high salt coexisted. The protein exhibited a single-peak elution behavior during a pH-step elution; nevertheless, the levels of soluble aggregates (i.e. high molecular weight species, HMW) in the CEX eluate were still found up to 12-fold higher than that for the load material. The amount of the aggregates formed upon the pH-step elution was dependent on column loading with maximum HMW achieved at intermediate loading levels, supporting the hypothesis that the aggregation was the result of both the conformational changes of the bound protein and the solution concentration of the aggregation-susceptible proteins during elution. Factors such as high load pH, short protein/resin contact time, hydrophilic resin surface, and weak ionizable ligand were effective, to some extent, to reduce aggregate formation by improving the structural integrity of the bound protein. An orthogonal technique, differential scanning fluorimetry (DSF) using Sypro Orange dye confirmed that the bound protein exposed more hydrophobic area than the native molecule in free solution, especially in the pH 4-5 range. The Sypro Orange dye study of resin surface property also demonstrated that the poly[styrene-divinylbenzene]-based Poros XS with polyhydroxyl surface coating is more hydrophobic compared to the agarose-based CM Sepharose FF and SP Sepharose FF. The hydrophobic property of Poros XS contributed to stronger interactions with the partially unfolded bound protein and consequently to the higher aggregate levels seen in Poros XS eluate. This work also investigates the aggregation reversibility in CEX eluate where up to 66% of the aggregates were observed to dissociate into native monomers over a period of 120h, and links the aggregate stability to such conditions as resin surface properties and charged ligand type. Experimental data was correlated semi-quantitatively with theoretical protein charge and hydrophobicity calculations using homology modeling within the BIOVIA Discovery Studio software. Finally, an arginine-sulphopropyl (Arg-SP) agarose resin immobilized with multi-functional ligands was prepared to verify the proposed hypothesis and to eliminate the aggregate formation. The findings of this work provide general insights in understanding aggregate formation and dissociation for structurally unstable proteins in the CEX step. Copyright © 2016 Elsevier B.V. All rights reserved.

Specific interactions between amyloid-β peptides in an amyloid-β hexamer with three-fold symmetry: Ab initio fragment molecular orbital calculations in water

NASA Astrophysics Data System (ADS)

Ishimura, Hiromi; Tomioka, Shogo; Kadoya, Ryushi; Shimamura, Kanako; Okamoto, Akisumi; Shulga, Sergiy; Kurita, Noriyuki

2017-03-01

The accumulation of amyloid-beta (Aβ) aggregates in brain contributes to the onset of Alzheimer's disease (AD). Recent structural analysis for the tissue obtained from AD patients revealed that Aβ aggregates have a single structure with three-fold symmetry. To explain why this structure possesses significant stability, we here investigated the specific interactions between Aβ peptides in the aggregate, using ab initio fragment molecular orbital calculations. The results indicate that the interactions between the Aβ peptides of the stacked Aβ pair are stronger than those between the Aβ peptides of the trimer with three-fold symmetry and that the charged amino-acids are important.

New Insights from Sum Frequency Generation Vibrational Spectroscopy into the Interactions of Islet Amyloid Polypeptides with Lipid Membranes

PubMed Central

Wang, Zhuguang; Batista, Victor S.; Yan, Elsa C. Y.

2016-01-01

Studies of amyloid polypeptides on membrane surfaces have gained increasing attention in recent years. Several studies have revealed that membranes can catalyze protein aggregation and that the early products of amyloid aggregation can disrupt membrane integrity, increasing water permeability and inducing ion cytotoxicity. Nonetheless, probing aggregation of amyloid proteins on membrane surfaces is challenging. Surface-specific methods are required to discriminate contributions of aggregates at the membrane interface from those in the bulk phase and to characterize protein secondary structures in situ and in real time without the use of perturbing spectroscopic labels. Here, we review the most recent applications of sum frequency generation (SFG) vibrational spectroscopy applied in conjunction with computational modeling techniques, a joint experimental and computational methodology that has provided valuable insights into the aggregation of islet amyloid polypeptide (IAPP) on membrane surfaces. These applications show that SFG can provide detailed information about structures, kinetics, and orientation of IAPP during interfacial aggregation, relevant to the molecular mechanisms of type II diabetes. These recent advances demonstrate the promise of SFG as a new approach for studying amyloid diseases at the molecular level and for the rational drug design targeting early aggregation products on membrane surfaces. PMID:26697504

Preventing α-synuclein aggregation: the role of the small heat-shock molecular chaperone proteins.

PubMed

Cox, Dezerae; Carver, John A; Ecroyd, Heath

2014-09-01

Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. The failure of proteostasis can result in the accumulation of non-native proteins leading to their aggregation and deposition in cells and in tissues. The amyloid fibrillar aggregation of the protein α-synuclein into Lewy bodies and Lewy neuritis is associated with neurodegenerative diseases classified as α-synucleinopathies, which include Parkinson's disease and dementia with Lewy bodies. The small heat-shock proteins (sHsps) are molecular chaperones that are one of the cell's first lines of defence against protein aggregation. They act to stabilise partially folded protein intermediates, in an ATP-independent manner, to maintain cellular proteostasis under stress conditions. Thus, the sHsps appear ideally suited to protect against α-synuclein aggregation, yet these fail to do so in the context of the α-synucleinopathies. This review discusses how sHsps interact with α-synuclein to prevent its aggregation and, in doing so, highlights the multi-faceted nature of the mechanisms used by sHsps to prevent the fibrillar aggregation of proteins. It also examines what factors may contribute to α-synuclein escaping the sHsp chaperones in the context of the α-synucleinopathies. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Assembly of Huntingtin headpiece into α-helical bundles.

PubMed

Ozgur, Beytullah; Sayar, Mehmet

2017-05-24

Protein aggregation is a hallmark of neurodegenerative disorders. In this group of brain-related disorders, a disease-specific "host" protein or fragment misfolds and adopts a metastatic, aggregate-prone conformation. Often, this misfolded conformation is structurally and thermodynamically different from its native state. Intermolecular contacts, which arise in this non-native state, promote aggregation. In this regard, understanding the molecular principles and mechanisms that lead to the formation of such a non-native state and further promote the formation of the critical nucleus for fiber growth is essential. In this study, the authors analyze the aggregation propensity of Huntingtin headpiece (htt NT ), which is known to facilitate the polyQ aggregation, in relation to the helix mediated aggregation mechanism proposed by the Wetzel group. The authors demonstrate that even though htt NT displays a degenerate conformational spectrum on its own, interfaces of macroscopic or molecular origin can promote the α-helix conformation, eliminating all other alternatives in the conformational phase space. Our findings indicate that htt NT molecules do not have a strong orientational preference for parallel or antiparallel orientation of the helices within the aggregate. However, a parallel packed bundle of helices would support the idea of increased polyglutamine concentration, to pave the way for cross-β structures.

Growth of Ni nanoclusters on irradiated graphene: a molecular dynamics study.

PubMed

Valencia, F J; Hernandez-Vazquez, E E; Bringa, E M; Moran-Lopez, J L; Rogan, J; Gonzalez, R I; Munoz, F

2018-04-23

We studied the soft landing of Ni atoms on a previously damaged graphene sheet by means of molecular dynamics simulations. We found a monotonic decrease of the cluster frequency as a function of its size, but few big clusters comprise an appreciable fraction of the total number of Ni atoms. The aggregation of Ni atoms is also modeled by means of a simple phenomenological model. The results are in clear contrast with the case of hard or energetic landing of metal atoms, where there is a tendency to form mono-disperse metal clusters. This behavior is attributed to the high diffusion of unattached Ni atoms, together with vacancies acting as capture centers. The findings of this work show that a simple study of the energetics of the system is not enough in the soft landing regime, where it is unavoidable to also consider the growth process of metal clusters.

A sensing approach for dopamine determination by boronic acid-functionalized molecularly imprinted graphene quantum dots composite

NASA Astrophysics Data System (ADS)

Zhou, Xi; Gao, Xuexia; Song, Fengyan; Wang, Chunpeng; Chu, Fuxiang; Wu, Shishan

2017-11-01

A novel fluorescence sensor was developed for dopamine (DA) determination based on molecularly imprinted graphene quantum dots and poly(indolylboronic acid) composite (MIPs@ PIn-BAc/GQDs). When the DA is added to the system, it leads to an aggregation and fluorescence quenching of the MIPs@ PIn-BAc/GQDs because of the covalent binding between the catechol group of DA and boronic acid. Such fluorescence behaviors are used for well testing DA in a range from 5 × 10-9 to 1.2 × 10-6 M with the detection limit of 2.5 × 10-9 M. Furthermore, the prepared sensors could well against the interferences from various biomolecules and be successfully used for the assay of DA in human biological samples, exhibiting excellent specificity. It is believed that the prepared MIPs@ PIn-BAc/GQDs hold great promise as a practical platform that can monitor DA level change.

New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

PubMed Central

Beugin, S; Edwards, K; Karlsson, G; Ollivon, M; Lesieur, S

1998-01-01

Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks. PMID:9635773

Influence of Inorganic Ions on Aggregation and Adsorption Behaviors of Human Adenovirus

EPA Science Inventory

In this study, we investigated the influence of inorganic ions on the aggregation and deposition (adsorption) behavior of human adenovirus (HAdV). Experiments were conducted to determine the surface charge and size of HAdV and viral adsorption capacity of sand in different salt c...

Influence of Inorganic Ions and Aggregation and Adsorption Behaviors of Human Adenovirus

EPA Science Inventory

In this study, influence of solution chemistries to the transport properties (aggregation and attachment behavior) of human adenovirus (HAdV) was investigated. Results showed isoelectric point (IEP) of HAdV in different salt conditions varied minimally, and it ranged from pH 3.5 ...

High Aggregate Stability Coefficients Can Be Obtained for Unstable Traits.

ERIC Educational Resources Information Center

Day, H. D.; Marshall, Dave

In the light of research by Epstein (1979) (which reported that error of measurement in the analysis of behavior stability may be reduced by examining the behavior of aggregate stability coefficients computed for measurements with known stability characteristics), this study examines stability coefficients for computer-generated data sets…

The influence of ion content on mobility and ion aggregation in PEO-based single-ion conductors

NASA Astrophysics Data System (ADS)

Caldwell, David; Maranas, Janna

2013-03-01

PEO-based ionomers reduce concentration polarization in solid polymer electrolytes by binding the anion to the polymer backbone. Ionomers have significant ion aggregation compared to PEO/salt systems, and the influence of these aggregates is unclear. When ion transport is coupled to the segmental dynamics of the polymer, aggregation will always reduce ion motion and conductivity. However, the conductivity of PEO ionomers is not sensitive to the degree of aggregation. We present results of molecular dynamics simulations where ion content is systematically varied. We consider the influence of ion content on ion aggregation, polymer mobility and cation motion.

A 3D Culture Model to Study How Fluid Pressure and Flow Affect the Behavior of Aggregates of Epithelial Cells.

PubMed

Piotrowski-Daspit, Alexandra S; Simi, Allison K; Pang, Mei-Fong; Tien, Joe; Nelson, Celeste M

2017-01-01

Cells are surrounded by mechanical stimuli in their microenvironment. It is important to determine how cells respond to the mechanical information that surrounds them in order to understand both development and disease progression, as well as to be able to predict cell behavior in response to physical stimuli. Here we describe a protocol to determine the effects of interstitial fluid flow on the migratory behavior of an aggregate of epithelial cells in a three-dimensional (3D) culture model. This protocol includes detailed methods for the fabrication of a 3D cell culture chamber with hydrostatic pressure control, the culture of epithelial cells as an aggregate in a collagen gel, and the analysis of collective cell behavior in response to pressure-driven flow.

Molecular dynamics simulations of aggregation of copper nanoparticles with different heating rates

NASA Astrophysics Data System (ADS)

Li, Qibin; Wang, Meng; Liang, Yunpei; Lin, Liyang; Fu, Tao; Wei, Peitang; Peng, Tiefeng

2017-06-01

Molecular dynamics simulations were employed to investigate the heating rates' effect on aggregation of two copper nanoparticles. The aggregation can be distinguished into three distinct regimes by the contacting and melting of nanoparticles. The nanoparticles contacting at a lower temperature during the sintering with lower heating rate, meanwhile, some temporary stacking fault exists at the contacting neck. The aggregation properties of the system, i.e. neck diameter, shrinkage ratio, potential energy, mean square displacement (MSD) and relative gyration radius, experience drastic changes due to the free surface annihilation. After the nanoparticles coalesced for a stable period, the shrinkage ratio, MSD, relative gyration radius and neck diameter of the system are dramatically changed during the melting process. It is shown that the shrinkage ratio and MSD have relative larger increasing ratio for a lower heating rate. While the evolution of the relative gyration radius and neck diameter is only sensitive to the temperature.

Non-steroidal anti-inflammatory drug naproxen destabilizes Aβ amyloid fibrils: A molecular dynamics investigation

PubMed Central

Takeda, Takako; Kumar, Rashmi; Raman, E. Prabhu; Klimov, Dmitri K.

2010-01-01

Using implicit solvent model and replica exchange molecular dynamics we examine the propensity of non-steroidal anti-inflammatory drug, naproxen, to interfere with Aβ fibril growth. We also compare the anti-aggregation propensity of naproxen with that of ibuprofen. Naproxen anti-aggregation effect is influenced by two factors. Similar to ibuprofen, naproxen destabilizes binding of incoming Aβ peptides to the fibril due to direct competition between the ligands and the peptides for the same binding location on the fibril surface (the edge). However, in contrast to ibuprofen naproxen binding also alters the conformational ensemble of Aβ monomers by promoting β-structure. The second factor weakens naproxen anti-aggregation effect. These findings appear to explain the experimental observations, according to which naproxen binds to Aβ fibril with higher affinity than ibuprofen, yet produces weaker anti-aggregation action. PMID:20979356

Molecular weight dependent structure and charge transport in MAPLE-deposited poly(3-hexylthiophene) thin films

DOE PAGES

Dong, Ban Xuan; Smith, Mitchell; Strzalka, Joseph; ...

2018-02-06

In this work, poly(3-hexylthiophene) (P3HT) films prepared using the matrix-assisted pulsed laser evaporation (MAPLE) technique are shown to possess morphological structures that are dependent on molecular weight (MW). Specifically, the structures of low MW samples of MAPLE-deposited film are composed of crystallites/aggregates embedded within highly disordered environments, whereas those of high MW samples are composed of aggregated domains connected by long polymer chains. Additionally, the crystallite size along the side-chain (100) direction decreases, whereas the conjugation length increases with increasing molecular weight. This is qualitatively similar to the structure of spin-cast films, though the MAPLE-deposited films are more disordered. In-planemore » carrier mobilities in the MAPLE-deposited samples increase with MW, consistent with the notion that longer chains bridge adjacent aggregated domains thereby facilitating more effective charge transport. The carrier mobilities in the MAPLE-deposited simples are consistently lower than those in the solvent-cast samples for all molecular weights, consistent with the shorter conjugation length in samples prepared by this deposition technique.« less

Molecular weight dependent structure and charge transport in MAPLE-deposited poly(3-hexylthiophene) thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Ban Xuan; Smith, Mitchell; Strzalka, Joseph

In this work, poly(3-hexylthiophene) (P3HT) films prepared using the matrix-assisted pulsed laser evaporation (MAPLE) technique are shown to possess morphological structures that are dependent on molecular weight (MW). Specifically, the structures of low MW samples of MAPLE-deposited film are composed of crystallites/aggregates embedded within highly disordered environments, whereas those of high MW samples are composed of aggregated domains connected by long polymer chains. Additionally, the crystallite size along the side-chain (100) direction decreases, whereas the conjugation length increases with increasing molecular weight. This is qualitatively similar to the structure of spin-cast films, though the MAPLE-deposited films are more disordered. In-planemore » carrier mobilities in the MAPLE-deposited samples increase with MW, consistent with the notion that longer chains bridge adjacent aggregated domains thereby facilitating more effective charge transport. The carrier mobilities in the MAPLE-deposited simples are consistently lower than those in the solvent-cast samples for all molecular weights, consistent with the shorter conjugation length in samples prepared by this deposition technique.« less

Molecular dynamics analysis of the aggregation propensity of polyglutamine segments

PubMed Central

Wen, Jingran; Scoles, Daniel R.

2017-01-01

Protein misfolding and aggregation is a pathogenic feature shared among at least ten polyglutamine (polyQ) neurodegenerative diseases. While solvent-solution interaction is a key factor driving protein folding and aggregation, the solvation properties of expanded polyQ tracts are not well understood. By using GPU-enabled all-atom molecular dynamics simulations of polyQ monomers in an explicit solvent environment, this study shows that solvent-polyQ interaction propensity decreases as the lengths of polyQ tract increases. This study finds a predominance in long-distance interactions between residues far apart in polyQ sequences with longer polyQ segments, that leads to significant conformational differences. This study also indicates that large loops, comprised of parallel β-structures, appear in long polyQ tracts and present new aggregation building blocks with aggregation driven by long-distance intra-polyQ interactions. Finally, consistent with previous observations using coarse-grain simulations, this study demonstrates that there is a gain in the aggregation propensity with increased polyQ length, and that this gain is correlated with decreasing ability of solvent-polyQ interaction. These results suggest the modulation of solvent-polyQ interactions as a possible therapeutic strategy for treating polyQ diseases. PMID:28542401

Aggregation Properties and Liquid Crystal Phase of a Dye Based on Naphthalenetetracarboxylic Acid

NASA Astrophysics Data System (ADS)

Tomasik, Michelle; Collings, Peter

2007-03-01

R003 is a dye produced for thin film optical components by Optiva, Inc.^1 made from the sulfonation of the dibenzimidazole derivative of naphthalenetetracarboxylic acid. Its molecular structure is very different from the aggregating food dye previously investigated in our laboratory^2 and R003 forms a liquid crystal phase at significantly lower concentrations. We have performed polarizing microscopy, absorption spectroscopy, and x-ray diffraction experiments in order to determine the phase diagram and aggregate structure. In addition, we have included both translational and orientational entropy in the theoretical analysis of the aggregation process, and have used a more realistic lineshape in analyzing the absorption data. Our results indicate that the ``bond energy'' for molecules in an aggregate is even larger than for the previously studied dye and that the aggregate structure has a cross-sectional area equal to two or three molecular areas rather than one.^1Lazarev, P., N. Ovchinnikova, M. Paukshto, SID Int. Symp. Digest of Tech. Papers, San Jose, California, June XXXII, 571 (2001).^2V. R. Horowitz, L. A. Janowitz, A. L. Modic, P. A. Heiney, and P. J. Collings, Phys. Rev. E 72, 041710 (2005).

Comparative analysis of thermal unfolding simulations of RNA recognition motifs (RRMs) of TAR DNA-binding protein 43 (TDP-43).

PubMed

Prakash, Amresh; Kumar, Vijay; Meena, Naveen Kumar; Hassan, Md Imtaiyaz; Lynn, Andrew M

2018-01-10

TAR DNA-binding protein 43 (TDP-43) inclusions have been found in Amyotrophic lateral sclerosis (ALS) and several other neurodegenerative diseases. Many studies suggest the involvement of RNA recognition motifs (RRMs) in TDP-43 proteinopathy. To elucidate the structural stability and the unfolding dynamics of RRMs, we have carried out atomistic molecular dynamics simulations at two different temperatures (300 and 500 K). The simulations results indicate that there are distinct structural differences in the unfolding pathway between the two domains and RRM1 unfolds faster than RRM2 in accordance with the lower thermal stability found experimentally. The unfolding behaviors of secondary structures showed that the α-helix was more stable than β-sheet and structural rearrangements of β-sheets results in formation of additional α-helices. At higher temperature, RRM1 exhibit increased overall flexibility and unfolding than RRM2. The temperature-dependent free energy landscapes consist of multiple metastable states stabilized by non-native contacts and hydrogen bonds in RRM2, thus rendering the RRM2 more prone to misfolding. The structural rearrangements of RRM2 could lead to aberrant protein-protein interactions that may account for enhanced aggregation and toxicity of TDP-43. Our analysis, thus identify the structural and thermodynamic characteristics of the RRMs of TDP-43, which will serve to uncover molecular mechanisms and driving forces in TDP-43 misfolding and aggregation.

Hydrogen bond dynamics of superheated water and methanol by ultrafast IR-pump and EUV-photoelectron probe spectroscopy.

PubMed

Vöhringer-Martinez, E; Link, O; Lugovoy, E; Siefermann, K R; Wiederschein, F; Grubmüller, H; Abel, B

2014-09-28

Supercritical water and methanol have recently drawn much attention in the field of green chemistry. It is crucial to an understanding of supercritical solvents to know their dynamics and to what extent hydrogen (H) bonds persist in these fluids. Here, we show that with femtosecond infrared (IR) laser pulses water and methanol can be heated to temperatures near and above their critical temperature Tc and their molecular dynamics can be studied via ultrafast photoelectron spectroscopy at liquid jet interfaces with high harmonics radiation. As opposed to previous studies, the main focus here is the comparison between the hydrogen bonded systems of methanol and water and their interpretation by theory. Superheated water initially forms a dense hot phase with spectral features resembling those of monomers in gas phase water. On longer timescales, this phase was found to build hot aggregates, whose size increases as a function of time. In contrast, methanol heated to temperatures near Tc initially forms a broad distribution of aggregate sizes and some gas. These experimental features are also found and analyzed in extended molecular dynamics simulations. Additionally, the simulations enabled us to relate the origin of the different behavior of these two hydrogen-bonded liquids to the nature of the intermolecular potentials. The combined experimental and theoretical approach delivers new insights into both superheated phases and may contribute to understand their different chemical reactivities.

Impact of aggregation on scaling behavior of Internet backbone traffic

NASA Astrophysics Data System (ADS)

Zhang, Zhi-Li; Ribeiro, Vinay J.; Moon, Sue B.; Diot, Christophe

2002-07-01

We study the impact of aggregation on the scaling behavior of Internet backbone tra ffic, based on traces collected from OC3 and OC12 links in a tier-1 ISP. We make two striking observations regarding the sub-second small time scaling behaviors of Internet backbone traffic: 1) for a majority of these traces, the Hurst parameters at small time scales (1ms - 100ms) are fairly close to 0.5. Hence the traffic at these time scales are nearly uncorrelated; 2) the scaling behaviors at small time scales are link-dependent, and stay fairly invariant over changing utilization and time. To understand the scaling behavior of network traffic, we develop analytical models and employ them to demonstrate how traffic composition -- aggregation of traffic with different characteristics -- affects the small-time scalings of network traffic. The degree of aggregation and burst correlation structure are two major factors in traffic composition. Our trace-based data analysis confirms this. Furthermore, we discover that traffic composition on a backbone link stays fairly consistent over time and changing utilization, which we believe is the cause for the invariant small-time scalings we observe in the traces.

Size-dependent interaction of silica nanoparticles with lysozyme and bovine serum albumin proteins

NASA Astrophysics Data System (ADS)

Yadav, Indresh; Aswal, Vinod K.; Kohlbrecher, Joachim

2016-05-01

The interaction of three different sized (diameter 10, 18, and 28 nm) anionic silica nanoparticles with two model proteins—cationic lysozyme [molecular weight (MW) 14.7 kDa)] and anionic bovine serum albumin (BSA) (MW 66.4 kDa) has been studied by UV-vis spectroscopy, dynamic light scattering (DLS), and small-angle neutron scattering (SANS). The adsorption behavior of proteins on the nanoparticles, measured by UV-vis spectroscopy, is found to be very different for lysozyme and BSA. Lysozyme adsorbs strongly on the nanoparticles and shows exponential behavior as a function of lysozyme concentration irrespective of the nanoparticle size. The total amount of adsorbed lysozyme, as governed by the surface-to-volume ratio, increases on lowering the size of the nanoparticles for a fixed volume fraction of the nanoparticles. On the other hand, BSA does not show any adsorption for all the different sizes of the nanoparticles. Despite having different interactions, both proteins induce similar phase behavior where the nanoparticle-protein system transforms from one phase (clear) to two phase (turbid) as a function of protein concentration. The phase behavior is modified towards the lower concentrations for both proteins with increasing the nanoparticle size. DLS suggests that the phase behavior arises as a result of the nanoparticles' aggregation on the addition of proteins. The size-dependent modifications in the interaction potential, responsible for the phase behavior, have been determined by SANS data as modeled using the two-Yukawa potential accounting for the repulsive and attractive interactions in the systems. The protein-induced interaction between the nanoparticles is found to be short-range attraction for lysozyme and long-range attraction for BSA. The magnitude of attractive interaction irrespective of protein type is enhanced with increase in the size of the nanoparticles. The total (attractive+repulsive) potential leading to two-phase formation is found to be more attractive for larger sized nanoparticles. The nanoparticle aggregates are characterized by mass fractal.

Derivatizing weak polyelectrolytes--solution properties, self-aggregation, and association with anionic surfaces of hydrophobically modified poly(ethylene imine).

PubMed

Griffiths, Peter C; Paul, Alison; Fallis, Ian A; Wellappili, Champa; Murphy, Damien M; Jenkins, Robert; Waters, Sarah J; Nilmini, Renuka; Heenan, Richard K; King, Stephen M

2007-10-15

The physical properties of weak polyelectrolytes may be tailored via hydrophobic modification to exhibit useful properties under appropriate pH and ionic strength conditions as a consequence of the often inherently competing effects of electrostatics and hydrophobicity. Pulsed-gradient spin-echo NMR (PGSE-NMR), electron paramagnetic resonance (EPR), small-angle neutron scattering (SANS) surface tension, fluorescence, and pH titration have been used to examine the solution conformation and aggregation behavior of a series of hydrophobically modified hyperbranched poly(ethylene imine) (PEI) polymers in aqueous solution, and their interaction with sodium dodecylsulfate (SDS). PGSE-NMR gave a particularly insightful picture of the apparent molecular weight distribution. The presence of the hydrophobes led to a lower effective charge on the polymer at any given pH, compared to the (parent) nonmodified samples. Analysis of the SANS data showed that the propensity to form highly elliptical or rod-like aggregates at higher pHs, reflecting both the changes in protonation behavior induced by the hydrophobic modification and an hydrophobic interaction, but that these structures were disrupted with decreasing pH (increasing charge). The parent samples were not surface active yet the hydrophobically modified samples show pronounced surface activity and the presence of small hydrophobic domains. The surface activity increased with an increase in the degree of modification. On addition of SDS, the onset of the formation of polymer/surfactant complexes was insensitive to the degree of modification with the resultant PEI/SDS complexes resembling the size and shape of simple SDS micelles. Indeed, the presence of the SDS effectively nullifies the effects of the hydrophobe. Hydrophobic modification is therefore a viable option to tailor pH dependent properties, whose effects may be removed by the presence of surfactant.

Molecular subtypes of Alzheimer's disease.

PubMed

Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Ghidoni, Roberta; Benussi, Luisa; Tonoli, Elisa; Giaccone, Giorgio; Moda, Fabio; Paterlini, Anna; Campagnani, Ilaria; Sorrentino, Stefano; Colombo, Laura; Kubis, Adriana; Bistaffa, Edoardo; Ghetti, Bernardino; Tagliavini, Fabrizio

2018-02-19

Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.

Lens protein composition, glycation and high molecular weight aggregation in aging rats.

PubMed

Swamy, M S; Abraham, E C

1987-10-01

Because of minimal or no turnover, lens proteins are subjected to substantial post-translational modifications which in turn disrupt lens architecture and change the optical properties leading to senile cataract formation. Progressive glycation is believed to have the potential to initiate the changes that are conducive to lens opacification. Fisher 344 rats were systematically followed from juvenile to older and aged phases of their life to study the relationship between lens glycation and high molecular weight (HMW) aggregate formation as well as quantitative and qualitative changes in lens crystallins. Levels of glycated proteins were quantified by affinity chromatography. Changes in lens crystallin composition and HMW aggregate formation were monitored by molecular sieve HPLC, further confirmed by SDS-PAGE and IEF techniques. As the age advances HMW and insoluble proteins increase with a concomitant disappearance of gamma-crystallins from soluble fraction. This disappearance of gamma-crystallins coincided with increased glycation (approximately 2-fold higher in insoluble fraction) and decreased sulfhydryl groups from soluble fraction. It appears that lens protein glycation, disappearance of gamma-crystallins and sulfhydryls from soluble fraction and increase of insoluble fraction and HMW aggregate are interrelated.

Regulating Molecular Aggregations of Polymers via Ternary Copolymerization Strategy for Efficient Solar Cells.

PubMed

Wang, Qian; Wang, Yingying; Zheng, Wei; Shahid, Bilal; Qiu, Meng; Wang, Di; Zhu, Dangqiang; Yang, Renqiang

2017-09-20

For many high-performance photovoltaic materials in polymer solar cells (PSCs), the active layers usually need to be spin-coated at high temperature due to the strong intermolecular aggregation of donor polymers, which is unfavorable in device repeatability and large-scale PSC printing. In this work, we adopted a ternary copolymerization strategy to regulate polymer solubility and molecular aggregation. A series of D-A 1 -D-A 2 random polymers based on different acceptors, strong electron-withdrawing unit ester substituted thieno[3,4-b]thiophene (TT-E), and highly planar dithiazole linked TT-E (DTzTT) were constructed to realize the regulation of molecular aggregation and simplification of device fabrication. The results showed that as the relative proportion of TT-E segment in the backbone increased, the absorption evidently red-shifted with a gradually decreased aggregation in solution, eventually leading to the active layers that can be fabricated at low temperature. Furthermore, due to the excellent phase separation and low recombination, the optimized solar cells based on the terpolymer P1 containing 30% of TT-E segment exhibit high power conversion efficiency (PCE) of 9.09% with a significantly enhanced fill factor up to 72.86%. Encouragingly, the photovoltaic performance is insensitive to the fabrication temperature of the active layer, and it still could maintain high PCE of 8.82%, even at room temperature. This work not only develops the highly efficient photovoltaic materials for low temperature processed PSCs through ternary copolymerization strategy but also preliminarily constructs the relationship between aggregation and photovoltaic performance.

Heat aggregation studies of phycobilisomes, ferritin, insulin, and immunoglobulin by dynamic light scattering.

PubMed

Singh, B P; Bohidar, H B; Chopra, S

1991-10-15

Dynamic laser light scattering studies on the heat aggregation behavior of phycobilisomes (PBS), ferritin, insulin, and immunoglobulin (IgG) in dilute aqueous solutions has been reported. Except for PBS, results are reported for heat aggregation trends in these proteins for three different pH environments (4.0, 7.5, 9.1). For PBS, studies were performed only in the neutral buffer medium (pH 7.5). The experiments were performed in the very dilute concentration regime (between 0.23 and 1.8 gL-1). For all these samples heat aggregation and dissociation trends were found to be linear with temperature. Upon temperature reversal (self-cooling), hysteresis-like behavior observed in insulin was found to be predominantly large at pH 7.5. PBS, ferritin, and IgG showed no such behavior at any of three pH values, and retraced their path of aggregation while dissociating on temperature reversal. Heat aggregation and dissociation processes in ferritin were found to be independent of pH. The IgG samples showed smooth aggregation tendency only up to 35 degrees C in the buffer media pH 4.0 and 9.1, whereas for pH 7.0 the same could be observed until 60 degrees C. Low polydispersity in the correlation spectra was observed in case of all these samples.

Granular activated carbon as nucleating agent for aerobic sludge granulation: Effect of GAC size on velocity field differences (GAC versus flocs) and aggregation behavior.

PubMed

Zhou, Jia-Heng; Zhao, Hang; Hu, Miao; Yu, Hai-Tian; Xu, Xiang-Yang; Vidonish, Julia; Alvarez, Pedro J J; Zhu, Liang

2015-12-01

Initial cell aggregation plays an important role in the formation of aerobic granules. In this study, three parallel aerobic granular sludge reactors treating low-strength wastewater were established using granular activated carbon (GAC) of different sizes as the nucleating agent. A novel visual quantitative evaluation method was used to discern how GAC size affects velocity field differences (GAC versus flocs) and aggregation behavior during sludge granulation. Results showed that sludge granulation was significantly enhanced by addition of 0.2mm GAC. However, there was no obvious improvement in granulation in reactor amended with 0.6mm GAC. Hydraulic analysis revealed that increase of GAC size enhanced the velocity field difference between flocs and GAC, which decreased the lifecycle and fraction of flocs-GAC aggregates. Overall, based on analysis of aggregation behavior, GAC of suitable sizes (0.2mm) can serve as the nucleating agent to accelerate flocs-GAC coaggregation and formation of aerobic granules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Modeling of Lipid Aggregates: Theory and Application

NASA Astrophysics Data System (ADS)

Fenner, Joel Stewart

The ability of cell membranes to perform a wide variety of biological functions stems from the organization and composition of its molecular constituents. There are many engineering applications, such as liposome drug delivery carriers, whose functionality takes advantage of the structure to function relationship of lipid membranes. The fundamental understanding of the relationship between the thermodynamic behavior and structure of lipid membranes and the molecular properties of their lipid constituents is crucial to the successful design of lipid related applications. However, information about how the local microscopic composition of lipid membranes responds to the presence of proteins and nanomaterials is challenging given the intrinsic experimental and theoretical difficulties of studying such small-scale systems. The present work generalizes a self consistent mean field theory for the study of the thermodynamic and structural behavior of lipid bilayers as a function of its molecular composition and physicochemical environments. This novel molecular theory provides with the ability of performing systematic thermodynamic calculations at relatively low computational costs while considering a detailed molecular description of the system under study. The competition of all relevant molecular interactions, such as electrostatics, vdW and chemical equilibria, in the membrane system is described. The developed molecular theory is applied to study how the protonation state of pH-sensitive amphiphiles in a membrane system affects the membrane's morphology. The molecular theory results demonstrate that the protonation state of ionizable groups within amphiphilic membranes shows a highly complex non-monotonic dependence on bulk salt concentration and pH strength. This result suggests that information about the pKa of the molecules is not sufficient to predict the protonation state of the ionizable groups in the membrane system. The molecular theory is also applied to study how the presence of proteins or functionalized nanoparticles near a multicomponent membrane surface leads to changes in its local membrane composition. The results support an electrostatic dependent recruitment mechanism of oncogenic RhoA proteins to the cell membrane. Finally, the molecular theory results describe how nanoparticle functionality and/or membrane molecular composition can be tuned to enhance or suppress nanoparticle adsorption on to phospholipid membranes.

Tuning of peptide assembly through force balance adjustment.

PubMed

Cao, Meiwen; Cao, Changhai; Zhang, Lijuan; Xia, Daohong; Xu, Hai

2013-10-01

Controlled self-assembly of amphiphilic tripeptides into distinct nanostructures is achieved via a controlled design of the molecular architecture. The tripeptide Ac-Phe-Phe-Lys-CONH2 (FFK), hardly soluble in water, forms long amyloid-like tubular structures with the aid of β-sheet hydrogen bonding and aromatic π-π stacking. Substitution of phenylalanine (F) with tyrosine (Y), that is, only a subtle structural variation in adding a hydroxyl group to the phenyl ring, results in great change in molecular self-assembly behavior. When one F is substituted with Y, the resulting molecules of FYK and YFK self-assemble into long thinner fibrils with high propensity for lateral association. When both Fs are substituted with Y, the resulting YYK molecule forms spherical aggregates. Introduction of hydroxyl groups into the molecule modifies aromatic interactions and introduces hydrogen bonding. Moreover, since the driving forces for peptide self-assembly including hydrogen bonding, electrostatic repulsion, and π-π stacking have high interdependence with each other, changes in aromatic interaction induce a Domino effect and cause a shift of force balance to a new state. This leads to significant variations in self-assembly behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

A Modular Library of Small Molecule Signals Regulates Social Behaviors in Caenorhabditis elegans

PubMed Central

Bose, Neelanjan; Zaslaver, Alon; Mahanti, Parag; Ho, Margaret C.; O'Doherty, Oran G.; Edison, Arthur S.; Sternberg, Paul W.; Schroeder, Frank C.

2012-01-01

The nematode C. elegans is an important model for the study of social behaviors. Recent investigations have shown that a family of small molecule signals, the ascarosides, controls population density sensing and mating behavior. However, despite extensive studies of C. elegans aggregation behaviors, no intraspecific signals promoting attraction or aggregation of wild-type hermaphrodites have been identified. Using comparative metabolomics, we show that the known ascarosides are accompanied by a series of derivatives featuring a tryptophan-derived indole moiety. Behavioral assays demonstrate that these indole ascarosides serve as potent intraspecific attraction and aggregation signals for hermaphrodites, in contrast to ascarosides lacking the indole group, which are repulsive. Hermaphrodite attraction to indole ascarosides depends on the ASK amphid sensory neurons. Downstream of the ASK sensory neuron, the interneuron AIA is required for mediating attraction to indole ascarosides instead of the RMG interneurons, which previous studies have shown to integrate attraction and aggregation signals from ASK and other sensory neurons. The role of the RMG interneuron in mediating aggregation and attraction is thought to depend on the neuropeptide Y-like receptor NPR-1, because solitary and social C. elegans strains are distinguished by different npr-1 variants. We show that indole ascarosides promote attraction and aggregation in both solitary and social C. elegans strains. The identification of indole ascarosides as aggregation signals reveals unexpected complexity of social signaling in C. elegans, which appears to be based on a modular library of ascarosides integrating building blocks derived from lipid β-oxidation and amino-acid metabolism. Variation of modules results in strongly altered signaling content, as addition of a tryptophan-derived indole unit to repellent ascarosides produces strongly attractive indole ascarosides. Our findings show that the library of ascarosides represents a highly developed chemical language integrating different neurophysiological pathways to mediate social communication in C. elegans. PMID:22253572

The aggregational status of cholera enterotoxin fragment A following biochemical fractionation.

PubMed

Knoop, F C

1978-01-01

Aggregates of frabment A of Vibrio cholerae enterotoxin were revealed following isoelectric focusing in 8 M urea of molecular sieve chromatography in 4% (v/v) formic acid. These aggregates consisted of dimers which required the presence of 10 M urea, 1% sodium dodecyl sulfate (SDS), 2 mM ethylenediaminetetracetic acid (EDTA) and heat (60 degrees C for 1 h) for complete dissociation. All aggregates were homogeneous when tested by standard analytical and SDS polyacrylamide gel electrophoresis or immunodiffusion analysis. Aggregates of fragment A were biologically active in the mouse Y1 adrenal cell assay.

Effect of polyacrylamide on soil physical and hydraulic properties

NASA Astrophysics Data System (ADS)

Albalasmeh, Ammar; Gharaibeh, Mamoun; Hamdan, Enas

2017-04-01

The effect of polyacrylamide (PAM), as a soil conditioner, on selected soil physical and hydraulic properties (infiltration rate (f(t)), hydraulic conductivity (HC), soil moisture content, aggregate stability (AS), and soil aggregation) was studied. Two types of anionic PAM were used: Low molecular weight (LPAM) (1×105 g/mol) with medium charge density (33-43) and high molecular weight (HPAM) (1-6×106 g/mol) with medium charge density (33-43). Sandy loam soil was packed into plastic columns; PAM solutions at different concentrations (100, 250, 500, and 1000 mg L-1) were used every two weeks in four wetting and drying cycles. The highest infiltration rate value was 0.16 mm s-1 at 1000 mg/L low molecular weight PAM while the highest value of infiltration rate in high PAM molecular weight was 0.11 mm s-1 compared to the control (0.01 mm s-1). Soil HC was about 3.00 cm h-1 for LPAM at 1000 mg L-1 PAM, while the highest value for HPAM was about 2 cm h-1 for the same concentration, compared to the control. The amount of water that can be held by soil increased with the addition of PAM compared to the control. Differences in water content were more pronounced in LPAM compared to HPAM. The addition of LPAM increased aggregate stability proportional to PAM concentration. Moreover, 1000 mg L-1 produced the highest aggregate stability (19{%}) compared to HPAM and control (7{%} and 5{%}), respectively. As PAM concentration increased, the geometric mean diameter (GMD) increased for both PAM molecular weights compared to control (0.4 mm). At 1000 mg L-1 the GMD values were 0.88 mm and 0.79 mm for LPAM and HPAM, respectively. The addition of PAM improved soil physical and hydraulic properties, with an advantage to LPAM owing that to its ability to penetrate soil aggregates and therefore stabilizing them.

Effect of degassing on the aggregation of carbon nanotubes dispersed in water

NASA Astrophysics Data System (ADS)

Chen, C.-J.; Huang, J.-R.; Hwang, I.-S.; Choi, H. J.; Lai, P.-Y.; Chan, C. K.

2017-10-01

Dynamic light scattering (DLS) along with centrifugation and shaking tests reveal that dissolved gases can significantly affect the aggregation behavior of carbon nanotubes (CNTs) dispersed in water. The CNTs in non-degassed samples form loose, stable networks having the DLS result reminiscent of semidilute polymer solutions, whereas the CNTs in degassed samples aggregate to form Brownian colloids that sediment quickly. Interestingly, the CNTs dispersed in acetone, with or without degassing, also behave like semidilute polymers in DLS experiments. We propose a surface nanobubble-assisted mechanism to explain the observed aggregation behaviors. Our work signifies that dissolved gases may play an important role in determining hydrophobicity and biomolecular functions in aqueous environments.

Size of spawning population, residence time, and territory shifts of individuals in the spawning aggregation of a riverine catostomid

USGS Publications Warehouse

Grabowski, T.B.; Isely, J.J.

2008-01-01

Little is known about the behavior of individual fish in a spawning aggregation, specifically how long an individual remains in an aggregation. We monitored Moxostoma robustum (Cope) (Robust Redhorse) in a Savannah River spawning aggregation during spring 2004 and 2005 to provide an estimate of the total number of adults and the number of males comprising the aggregation and to determine male residence time and movements within a spawning aggregation. Robust Redhorse were captured using prepostioned grid electrofishers, identified to sex, weighed, measured, and implanted with a passive integrated transponder. Spawning aggregation size was estimated using a multiple census mark-and-recapture procedure. The spawning aggregation seemed to consist of approximately the same number of individuals (82-85) and males (50-56) during both years of this study. Individual males were present for a mean of 3.6 ?? 0.24 days (?? SE) during the 12-day spawning period. The mean distance between successive recaptures of individual males was 15.9 ?? 1.29 m (?? SE). We conclude that males establish spawning territories on a daily basis and are present within the spawning aggregation for at least 3-4 days. The relatively short duration of the aggregation may be the result of an extremely small population of adults. However, the behavior of individuals has the potential to influence population estimates made while fish are aggregated for spawning.

Aggregate Timber Supply: From the Forest to the Market

Treesearch

David N. Wear; Subhrendu K. Pattanayak

2003-01-01

Timber supply modeling is a means of formalizing the production behavior of heterogeneous landowners managing a wide variety of forest types and vintages within a region. The critical challenge of timber supply modeling is constructing theoretically valid and empirically practical aggregate descriptions of harvest behavior. Understanding timber supply is essential for...

Parasitoid aggregation and the stabilization of a salt marsh host-parasitoid system

Treesearch

John D. Reeve; James T. Cronin; Donald R. Strong

1994-01-01

We examine a salt marsh host-parasitoid system, consisting of the planthopper Prokelisia marginata and its egg parasitoid Anagrus delicatus, for evidence of stabilizing parasitoid behavior. We first determine if there is sufficient parasitoid aggregation to potentially stabilize the Prokelisia-Anagrus interactions, using methods that infer parasitoid behavior from the...

Aggregation and feeding behavior of the formosan subterranean termite (Isoptera: Rhinotermitidae) on wood decayed by three species of wood rot fungi

USDA-ARS?s Scientific Manuscript database

Aggregation and feeding behavior of the Formosan subterranean termite, Coptotermes formosanus Shiraki, was evaluated on wood decayed by three species of fungus that use different enzymatic pathways to degrade lignocellulose, the brown rot fungus, Gloeophyllum trabeum and two white rot fungi, Phanero...

Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus.

PubMed

Rezaei-Ghaleh, Nasrollah; Kumar, Sathish; Walter, Jochen; Zweckstetter, Markus

2016-07-29

Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-β (Aβ) peptide and investigate how phosphorylation at serine 8 affects the structure of Aβ aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric Aβ, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that Aβ phosphorylation at serine 8 causes structural changes in the N-terminal region of Aβ aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of Aβ aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Factors that drive peptide assembly and fibril formation: experimental and theoretical analysis of Sup35 NNQQNY mutants.

PubMed

Do, Thanh D; Economou, Nicholas J; LaPointe, Nichole E; Kincannon, William M; Bleiholder, Christian; Feinstein, Stuart C; Teplow, David B; Buratto, Steven K; Bowers, Michael T

2013-07-18

Residue mutations have substantial effects on aggregation kinetics and propensities of amyloid peptides and their aggregate morphologies. Such effects are attributed to conformational transitions accessed by various types of oligomers such as steric zipper or single β-sheet. We have studied the aggregation propensities of six NNQQNY mutants: NVVVVY, NNVVNV, NNVVNY, VIQVVY, NVVQIY, and NVQVVY in water using a combination of ion-mobility mass spectrometry, transmission electron microscopy, atomic force microscopy, and all-atom molecular dynamics simulations. Our data show a strong correlation between the tendency to form early β-sheet oligomers and the subsequent aggregation propensity. Our molecular dynamics simulations indicate that the stability of a steric zipper structure can enhance the propensity for fibril formation. Such stability can be attained by either hydrophobic interactions in the mutant peptide or polar side-chain interdigitations in the wild-type peptide. The overall results display only modest agreement with the aggregation propensity prediction methods such as PASTA, Zyggregator, and RosettaProfile, suggesting the need for better parametrization and model peptides for these algorithms.

A Putative Biochemical Engram of Long-Term Memory.

PubMed

Li, Liying; Sanchez, Consuelo Perez; Slaughter, Brian D; Zhao, Yubai; Khan, Mohammed Repon; Unruh, Jay R; Rubinstein, Boris; Si, Kausik

2016-12-05

How a transient experience creates an enduring yet dynamic memory remains an unresolved issue in studies of memory. Experience-dependent aggregation of the RNA-binding protein CPEB/Orb2 is one of the candidate mechanisms of memory maintenance. Here, using tools that allow rapid and reversible inactivation of Orb2 protein in neurons, we find that Orb2 activity is required for encoding and recall of memory. From a screen, we have identified a DNA-J family chaperone, JJJ2, which facilitates Orb2 aggregation, and ectopic expression of JJJ2 enhances the animal's capacity to form long-term memory. Finally, we have developed tools to visualize training-dependent aggregation of Orb2. We find that aggregated Orb2 in a subset of mushroom body neurons can serve as a "molecular signature" of memory and predict memory strength. Our data indicate that self-sustaining aggregates of Orb2 may serve as a physical substrate of memory and provide a molecular basis for the perduring yet malleable nature of memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Spatial distribution pattern of Pontania dolichura larvae and sampling technique].

PubMed

Zhang, Feng; Chen, Zhijie; Zhang, Shulian; Zhao, Huiyan

2006-03-01

In this paper, the spatial distribution pattern of Pontania dolichura larvae was analyzed with Taylor's power law, Iwao's distribution function, and six aggregation indexes. The results showed that the spatial distribution pattern of P. dolichura larvae was of aggregated, and the basic component of the distribution was individual colony, with the aggregation intensity increased with density. On branches, the aggregation was caused by the adult behavior of laying eggs and the spatial position of leaves, while on leaves, the aggregation was caused by the spatial position of news leaves in spring when m < 2.37, and by the spatial position of news leaves in spring and the behavior of eclosion and laying eggs when m > 2.37. By using the parameters alpha and beta in Iwao's m * -m regression equation, the optimal and sequential sampling numbers were determined.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, Johannes; German Center for Neurodegenerative Diseases – DZNE, Site Munich, Feodor-Lynen-Str. 17, 81377 Munich; Hillmer, Andreas S.

Synucleinopathies such as dementia with Lewy bodies or Parkinson’s disease are characterized by intracellular deposition of pathologically aggregated α-synuclein. The details of the molecular pathogenesis of PD and especially the conditions that lead to intracellular aggregation of α-synuclein and the role of these aggregates in cell death remain unknown. In cell free in vitro systems considerable knowledge about the aggregation processes has been gathered. In comparison, the knowledge about these aggregation processes in cells is far behind. In cells α-synuclein aggregates can be toxic. However, the crucial particle species responsible for decisive steps in pathogenesis such as seeding a continuing aggregationmore » process and triggering cell death remain to be identified. In order to understand the complex nature of intracellular α-synuclein aggregate formation, we analyzed fluorescent particles formed by venus and α-synuclein-venus fusion proteins and α-synuclein-hemi-venus fusion proteins derived from gently lyzed cells. With these techniques we were able to identify and characterize α-synuclein oligomers formed in cells. Especially the use of α-synuclein-hemi-venus fusion proteins enabled us to identify very small α-synuclein oligomers with high sensitivity. Furthermore, we were able to study the molecular effect of heat shock protein 70, which is known to inhibit α-synuclein aggregation in cells. Heat shock protein 70 does not only influence the size of α-synuclein oligomers, but also their quantity. In summary, this approach based on fluorescence single particle spectroscopy, that is suited for high throughput measurements, can be used to detect and characterize intracellularly formed α-synuclein aggregates and characterize the effect of molecules that interfere with α-synuclein aggregate formation. - Highlights: • Single particle spectroscopy detects intracellular formed α-synuclein aggregates. • Fusion proteins allow detection of protein aggregates at the oligomer level. • The technique detects molecules inhibiting α-synuclein aggregate formation. • Single particle spectroscopy is suited for high throughput measurements.« less

Porosity and permeability studies of Virginia aggregates : final report.

DOT National Transportation Integrated Search

1972-01-01

It is generally recognized that the volume and geometry of included pores within a mineral aggregate have a significant effect on the physical and chemical behavior of the aggregate when used as a structural material. However due to the technical dif...

High-molecular weight Aβ oligomers and protofibrils are the predominant Aβ species in the native soluble protein fraction of the AD brain.

PubMed

Upadhaya, Ajeet Rijal; Lungrin, Irina; Yamaguchi, Haruyasu; Fändrich, Marcus; Thal, Dietmar Rudolf

2012-02-01

Alzheimer's disease (AD) is characterized by the aggregation and deposition of amyloid β protein (Aβ) in the brain. Soluble Aβ oligomers are thought to be toxic. To investigate the predominant species of Aβ protein that may play a role in AD pathogenesis, we performed biochemical analysis of AD and control brains. Sucrose buffer-soluble brain lysates were characterized in native form using blue native (BN)-PAGE and also in denatured form using SDS-PAGE followed by Western blot analysis. BN-PAGE analysis revealed a high-molecular weight smear (>1000 kD) of Aβ(42) -positive material in the AD brain, whereas low-molecular weight and monomeric Aβ species were not detected. SDS-PAGE analysis, on the other hand, allowed the detection of prominent Aβ monomer and dimer bands in AD cases but not in controls. Immunoelectron microscopy of immunoprecipitated oligomers and protofibrils/fibrils showed spherical and protofibrillar Aβ-positive material, thereby confirming the presence of high-molecular weight Aβ (hiMWAβ) aggregates in the AD brain. In vitro analysis of synthetic Aβ(40) - and Aβ(42) preparations revealed Aβ fibrils, protofibrils, and hiMWAβ oligomers that were detectable at the electron microscopic level and after BN-PAGE. Further, BN-PAGE analysis exhibited a monomer band and less prominent low-molecular weight Aβ (loMWAβ) oligomers. In contrast, SDS-PAGE showed large amounts of loMWAβ but no hiMWAβ(40) and strikingly reduced levels of hiMWAβ(42) . These results indicate that hiMWAβ aggregates, particularly Aβ(42) species, are most prevalent in the soluble fraction of the AD brain. Thus, soluble hiMWAβ aggregates may play an important role in the pathogenesis of AD either independently or as a reservoir for release of loMWAβ oligomers. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Pragmatic precision oncology: the secondary uses of clinical tumor molecular profiling

PubMed Central

Thota, Ramya; Staggs, David B; Johnson, Douglas B; Warner, Jeremy L

2016-01-01

Background Precision oncology increasingly utilizes molecular profiling of tumors to determine treatment decisions with targeted therapeutics. The molecular profiling data is valuable in the treatment of individual patients as well as for multiple secondary uses. Objective To automatically parse, categorize, and aggregate clinical molecular profile data generated during cancer care as well as use this data to address multiple secondary use cases. Methods A system to parse, categorize and aggregate molecular profile data was created. A naÿve Bayesian classifier categorized results according to clinical groups. The accuracy of these systems were validated against a published expertly-curated subset of molecular profiling data. Results Following one year of operation, 819 samples have been accurately parsed and categorized to generate a data repository of 10,620 genetic variants. The database has been used for operational, clinical trial, and discovery science research. Conclusions A real-time database of molecular profiling data is a pragmatic solution to several knowledge management problems in the practice and science of precision oncology. PMID:27026612

Self-organization in suspensions of end-functionalized semiflexible polymers under shear flow

NASA Astrophysics Data System (ADS)

Myung, Jin Suk; Winkler, Roland G.; Gompper, Gerhard

2015-12-01

The nonequilibrium dynamical behavior and structure formation of end-functionalized semiflexible polymer suspensions under flow are investigated by mesoscale hydrodynamic simulations. The hybrid simulation approach combines the multiparticle collision dynamics method for the fluid, which accounts for hydrodynamic interactions, with molecular dynamics simulations for the semiflexible polymers. In equilibrium, various kinds of scaffold-like network structures are observed, depending on polymer flexibility and end-attraction strength. We investigate the flow behavior of the polymer networks under shear and analyze their nonequilibrium structural and rheological properties. The scaffold structure breaks up and densified aggregates are formed at low shear rates, while the structural integrity is completely lost at high shear rates. We provide a detailed analysis of the shear- rate-dependent flow-induced structures. The studies provide a deeper understanding of the formation and deformation of network structures in complex materials.

Characterization of Aggregation Propensity of a Human Fc-Fusion Protein Therapeutic by Hydrogen/Deuterium Exchange Mass Spectrometry

NASA Astrophysics Data System (ADS)

Huang, Richard Y.-C.; Iacob, Roxana E.; Krystek, Stanley R.; Jin, Mi; Wei, Hui; Tao, Li; Das, Tapan K.; Tymiak, Adrienne A.; Engen, John R.; Chen, Guodong

2017-05-01

Aggregation of protein therapeutics has long been a concern across different stages of manufacturing processes in the biopharmaceutical industry. It is often indicative of aberrant protein therapeutic higher-order structure. In this study, the aggregation propensity of a human Fc-fusion protein therapeutic was characterized. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was applied to examine the conformational dynamics of dimers collected from a bioreactor. HDX-MS data combined with spatial aggregation propensity calculations revealed a potential aggregation interface in the Fc domain. This study provides a general strategy for the characterization of the aggregation propensity of Fc-fusion proteins at the molecular level.

Photophysical and morphological implications of single-strand conjugated polymer folding in solution

DOE PAGES

Fauvell, Thomas J.; Zheng, Tianyue; Jackson, Nicholas E.; ...

2016-04-08

Organic semiconductors have garnered substantial interest in optoelectronics, but their device performances exhibit strong dependencies on material crystallinity and packing. In an effort to understand the interactions dictating the morphological and photophysical properties of a high-performing photovoltaic polymer, PTB7, a series of short oligomers and low molecular weight polymers of PTB7 were synthesized. Chain-length dependent optical studies of these oligomers demonstrate that PTB7’s low-energy visible absorption is largely due to self-aggregation-induced ordering, rather than in-chain charge transfer, as previously thought. By examining molecular weight and concentration dependent optical properties, supplemented by molecular dynamics simulations, we attribute polymeric PTB7’s unique midgapmore » fluorescence and concentration independent absorption spectrum to an interplay between low molecular weight unaggregated strands and high-molecular weight self-aggregated (folded) strands. Specifically, we propose that the onset of PTB7 self-folding occurs between 7 and 13 repeat units, but the aggregates characteristic of polymeric PTB7 only develop at lengths of ~30 repeat units. Atomistic molecular dynamics simulations of PTB7 corroborate these conclusions, and a simple relation is proposed which quantifies the free-energy of conjugated polymer folding. Lastly, this study provides detailed guidance in the design of intra- and interchain contributions to the photophysical and morphological properties of polymeric semiconductors.« less

Formation of Ordered Arrays of Proteins on Surfaces

NASA Technical Reports Server (NTRS)

Lenhoff, A. M.

1996-01-01

Van der Waals (dispersion) forces contribute to interactions of proteins with other molecules or with surfaces, but because of the structural complexity of protein molecules, the magnitude of these effects is usually estimated based on idealized models of the molecular geometry, e.g., spheres or spheroids. The calculations reported here seek to account for both the geometric irregularity of protein molecules and the material properties of the interacting media. While the latter are found to fall in the generally accepted range, the molecular shape is shown to cause the magnitudes of the interactions to differ significantly from those calculated using idealized models, with important consequences. First, the roughness of the molecular surface leads to much lower average interaction energies for both protein-protein and protein-surface cases relative to calculations in which the protein molecule is approximated as a sphere. These results indicate that a form of steric stabilization may be an important effect in protein solutions. Underlying this behavior is appreciable orientational dependence, one reflection of which is that molecules of complementary shape are found to exhibit very strong attractive dispersion interactions. Although this has been widely discussed previously in the context of molecular recognition processes, the broader implications of these phenomena may also be important at larger molecular separations, e.g., in the dynamics of aggregation, precipitation and crystal growth.

Van der Waals Interactions Involving Proteins

NASA Technical Reports Server (NTRS)

Roth, Charles M.; Neal, Brian L.; Lenhoff, Abraham M.

1996-01-01

Van der Waals (dispersion) forces contribute to interactions of proteins with other molecules or with surfaces, but because of the structural complexity of protein molecules, the magnitude of these effects is usually estimated based on idealized models of the molecular geometry, e.g., spheres or spheroids. The calculations reported here seek to account for both the geometric irregularity of protein molecules and the material properties of the interacting media. Whereas the latter are found to fall in the generally accepted range, the molecular shape is shown to cause the magnitudes of the interactions to differ significantly from those calculated using idealized models. with important consequences. First, the roughness of the molecular surface leads to much lower average interaction energies for both protein-protein and protein-surface cases relative to calculations in which the protein molecule is approximated as a sphere. These results indicate that a form of steric stabilization may be an important effect in protein solutions. Underlying this behavior is appreciable orientational dependence, one reflection of which is that molecules of complementary shape are found to exhibit very strong attractive dispersion interactions. Although this has been widely discussed previously in the context of molecular recognition processes, the broader implications of these phenomena may also be important at larger molecular separations, e.g., in the dynamics of aggregation, precipitation, and crystal growth.

Comparison and Analysis of 3,4 dihydrocylmandelic acid (DHMA) and noremetanephrine (NMN) on Amyloid-Beta 40 Monomer for treatment of Alzheimer's Disease using Molecular Dynamics Simulation

NASA Astrophysics Data System (ADS)

Choi, Woosung; Jee, Sang Eun; Jang, Seung Soon

Alzheimer's disease (AD) is type of degenerative dementia caused memory loss and behavior problem. Main reason of AD is Amyloid-Beta 40(A β) mostly composed of α -helix form misfolds to insoluble fibrils and soluble oilgomer. This insoluble fibrils aggregate with beta sheet structure and form the plaque which is caused nurotoxicity in brain. Both 3,4 dihydrocylmandelic acid (DHMA) and noremetanephrine (NMN) are the metabolite of norepinephrine in brain . Also these are inhibit the changing formation of fibrils and maintain the α -helix structure. In this computational modeling study, both NMN and DHMA molecules were modified and analyzed for specific effect on the A β-monomer using molecular dynamics simulation. Using molecular dynamic simulation, NMN and DHMA act as modulator on three A β-monomer batches and could observe the conformational changing of these A β-monomer under the physiologocal condition. This computational experiment is designed to compare and analyze both of chemicals for determining which chamecal would be more effective on the conformation of A β 40 monomer.

Variation is function: Are single cell differences functionally important?: Testing the hypothesis that single cell variation is required for aggregate function.

PubMed

Dueck, Hannah; Eberwine, James; Kim, Junhyong

2016-02-01

There is a growing appreciation of the extent of transcriptome variation across individual cells of the same cell type. While expression variation may be a byproduct of, for example, dynamic or homeostatic processes, here we consider whether single-cell molecular variation per se might be crucial for population-level function. Under this hypothesis, molecular variation indicates a diversity of hidden functional capacities within an ensemble of identical cells, and this functional diversity facilitates collective behavior that would be inaccessible to a homogenous population. In reviewing this topic, we explore possible functions that might be carried by a heterogeneous ensemble of cells; however, this question has proven difficult to test, both because methods to manipulate molecular variation are limited and because it is complicated to define, and measure, population-level function. We consider several possible methods to further pursue the hypothesis that variation is function through the use of comparative analysis and novel experimental techniques. © 2015 The Authors. BioEssays published by WILEY Periodicals, Inc.

Molecular organization of various collagen fragments as revealed by atomic force microscopy and diffusion-ordered NMR spectroscopy.

PubMed

Stötzel, Sabine; Schurink, Marloes; Wienk, Hans; Siebler, Uschi; Burg-Roderfeld, Monika; Eckert, Thomas; Kulik, Bianca; Wechselberger, Rainer; Sewing, Judith; Steinmeyer, Jürgen; Oesser, Steffen; Boelens, Rolf; Siebert, Hans-Christian

2012-09-17

Heterogeneous mixtures of collagen fragments can be used as nutrition supplement or as key ingredients for ointments with therapeutic relevance in wound healing. Some mixtures of collagen fragments are referred to as collagen hydrolysates owing to the production process with hydrolytic enzymes. Since the precise composition of collagen hydrolysates is generally unknown, it is of interest to analyze samples containing various collagen fragments with appropriate biophysical methods. Any product optimization without a profound knowledge concerning the size and the molecular weight distribution of its components is nearly impossible. It turned out that a combination of AFM methods with NMR techniques is exceptionally suited to examine the size range and the aggregation behavior of the collagen fragments in the hydrolysates of fish, jellyfish, chicken, porcine and bovine collagen. Supported by molecular modeling calculations, the AFM and NMR experiments provide a detailed knowledge about the composition of collagen hydrolysates and collagen ointments. Furthermore, the data allow a correlation between the size of the fragments and their potential bioactivity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kinetics of a Migration-Driven Aggregation-Fragmentation Process

NASA Astrophysics Data System (ADS)

Zhuang, You-Yi; Lin, Zhen-Quan; Ke, Jian-Hong

2003-08-01

We propose a reversible model of the migration-driven aggregation-fragmentation process with the symmetric migration rate kernels K(k;j)=K^'(k;j)=λ kj^v and the constant aggregation rates I1, I2 and fragmentation rates J1, J2. Based on the mean-field theory, we investigate the evolution behavior of the aggregate size distributions in several cases with different values of index υ. We find that the fragmentation reaction plays a more important role in the kinetic behaviors of the system than the aggregation and migration. When J1=0 and J2 =0, the aggregate size distributions ak(t) and bk(t) obey the conventional scaling law, while when J1>0 and J2>0, they obey the modified scaling law with an exponential scaling function. The total mass of either species remains conserved. The project supported by National Natural Science Foundation of China under Grant Nos. 10275048 and 10175008, and Natural Science Foundation of Zhejiang Province of China under Grant No. 102067

Thermodynamics of Protein Aggregation

NASA Astrophysics Data System (ADS)

Osborne, Kenneth L.; Barz, Bogdan; Bachmann, Michael; Strodel, Birgit

Amyloid protein aggregation characterizes many neurodegenerative disorders, including Alzheimer's, Parkinson's, and Creutz- feldt-Jakob disease. Evidence suggests that amyloid aggregates may share similar aggregation pathways, implying simulation of full-length amyloid proteins is not necessary for understanding amyloid formation. In this study we simulate GNNQQNY, the N-terminal prion-determining domain of the yeast protein Sup35 to investigate the thermodynamics of structural transitions during aggregation. We use a coarse-grained model with replica-exchange molecular dynamics to investigate the association of 3-, 6-, and 12-chain GNNQQNY systems and we determine the aggregation pathway by studying aggregation states of GN- NQQNY. We find that the aggregation of the hydrophilic GNNQQNY sequence is mainly driven by H-bond formation, leading to the formation of /3-sheets from the very beginning of the assembly process. Condensation (aggregation) and ordering take place simultaneously, which is underpinned by the occurrence of a single heat capacity peak only.

Peptide aggregation and solvent electrostriction in a simple zwitterionic dipeptide via molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Tulip, P. R.; Bates, S. P.

2009-07-01

We investigate the structure of the glycyl-l-alanine dipeptide in aqueous solution at a 1:20 peptide:water concentration via classical, atomistic molecular dynamics simulations using the CHARMM22 force field, and compare to recent neutron diffraction data [S. E. McLain, A. K. Soper, and A. Watts, Eur. Biophys. J. 37, 647 (2008); S. E. McLain, A. K. Soper, I. Diadone, J. C. Smith, and A. Watts, Angew. Chem. Int. Ed. 47, 9059 (2008)]. Comparison between simulations and experiments is made using the static structure factor S (Q ) . The effect of water model (TIP3P, TIP4P, and SPC/E) upon the solution structure is investigated. Agreement between experiment and simulation is generally good across the entire Q range, although some model-dependent variation is observed, particularly in the predicted intensities of features in S (Q ) . Peptide aggregation is found to be driven by "hydrophilic" (often bifurcated) hydrogen bonds formed between carboxy and amine functional groups, although simulations suggest that the degree of aggregation is less than that observed experimentally. It is found that hydrophobic association is not significant, with hydrophobic hydration being preferred to association. Detailed examination of the solute structural motifs reveals the existence of bifurcated motifs that are suggested to be an artifact of the CHARMM force field, and may imply that classical force fields provide a flawed structural and dynamical description of such molecular fluids. Investigation of the water structure reveals the presence of an electrostrictive effect which manifests itself as an increase in the number of interstitial molecules in the water second coordination shell, in contradiction to suggestions that this phenomenon arises owing to hydrogen bond bending. Detailed analysis based upon two-dimensional distribution functions suggests an intimate link between the phenomenon of electrostriction and the behavior of water under high-pressure compression. We find the magnitude of the electrostrictive effect inferred from the neutron diffraction data to be greater than that found in the simulations. Investigation of the solvation structure suggests that the CHARMM force field overhydrates the terminal carboxy group, and that this overhydration is accompanied by the presence of bifurcated hydrogen bonds.

Aggregate development in C 60/N-methyl-2-pyrrolidone solution and its mixture with water as revealed by extraction and mass spectroscopy

NASA Astrophysics Data System (ADS)

Kyzyma, O. A.; Korobov, M. V.; Avdeev, M. V.; Garamus, V. M.; Snegir, S. V.; Petrenko, V. I.; Aksenov, V. L.; Bulavin, L. A.

2010-06-01

The aggregate development in C 60/N-methyl-2-pyrrolidone (C 60/NMP) solution with time is studied by the extraction (hexane) and mass spectroscopy. It is shown that only molecular C 60 in NMP is extracted in hexane, which makes it possible to follow a change in the concentration of non-aggregated fullerene in C 60/NMP during the aggregate growth. It is concluded that almost all fullerene dissolved in NMP is in the aggregates after one month. The reorganization of the aggregates is detected when water is added to the aggregated solution C 60/NMP. Both methods prove that in this case individual fullerene molecules are detached from the aggregates, which contradicts somewhat to complete insolubility of C 60 in water.

Sensitive and molecular size-selective detection of proteins using a chip-based and heteroliganded gold nanoisland by localized surface plasmon resonance spectroscopy

NASA Astrophysics Data System (ADS)

Hong, Surin; Lee, Suseung; Yi, Jongheop

2011-04-01

A highly sensitive and molecular size-selective method for the detection of proteins using heteroliganded gold nanoislands and localized surface plasmon resonance (LSPR) is described. Two different heteroligands with different chain lengths (3-mercaptopionicacid and decanethiol) were used in fabricating nanoholes for the size-dependent separation of a protein in comparison with its aggregate. Their ratios on gold nanoisland were optimized for the sensitive detection of superoxide dismutase (SOD1). This protein has been implicated in the pathology of amyotrophic lateral sclerosis (ALS). Upon exposure of the optimized gold nanoisland to a solution of SOD1 and aggregates thereof, changes in the LSPR spectra were observed which are attributed to the size-selective and covalent chemical binding of SOD1 to the nanoholes. With a lower detection limit of 1.0 ng/ml, the method can be used to selectively detect SOD1 in the presence of aggregates at the molecular level.

Monitoring aggregate disintegration with laser diffraction: A tool for studying soils as sediments

NASA Astrophysics Data System (ADS)

Mason, Joseph; Kasmerchak, Chase; Liang, Mengyu

2016-04-01

One of the more important characteristics of soil that becomes hillslope, fluvial, or aeolian sediment is the presences of aggregates, which disintegrate at varying rates and to varying degrees during transport. Laser diffraction particle size analyzers allow monitoring of aggregate disintegration as a sample of soil or sediment suspended in water is circulated continuously through the measurement cell (Bieganowski et al., 2010, Clay Minerals 45-23-34; Mason et al., Catena 87:107-118). Mason et al. (2011) applied this approach to aeolian sedimentary aggregates (e.g. clay pellets eroded from dry lakebeds), immersing dry samples in DI water and circulating them through a Malvern Mastersizer 2000 particle size analyzer for three hours while repeated size distribution (SD) measurements were made. A final measurement was made after sonication and treatment with Na-metaphosphate. In that study, most samples approached a steady SD within three hours, which included both primary mineral grains and persistent aggregates. The disintegration process could be modeled with a first-order rate law representing the disintegration of a single population of aggregates. A wide range of model parameters were observed among the samples studied, and it was suggested that they could be useful in predicting the behavior of these aggregates, under rainfall impact and during slopewash or fluvial transport. Addition of Ca++ to the suspension altered aggregate behavior in some but not all cases. We applied the same method to dry, unground material from upper horizons of soils sampled along a bioclimatic gradient in northern Minnesota, USA, all formed in lithologically similar glacigenic sediment. These ranged from Alfisols (Luvisols) formed under forest since the last deglaciation, to Alfisols under forest that more recently replaced grassland, and Mollisols (Chernozems) that formed entirely under grassland vegetation. Few of these soil samples approached a steady SD within three hours, and modeling aggregate disintegration required the assumption of at least two aggregate populations. Upper horizons of soils formed under grassland displayed relatively slow disintegration throughout the procedure, with a large proportion of aggregates remaining after three hours. E horizons from forest soils, with low organic matter (OM) and clay content, displayed rapid early distintegration of a large portion of the aggregates, followed by much slower breakdown of the remainder (i.e. the two populations modeled had very different rate constants). OM content is clearly the overriding control on aggregate behavior, but we are also exploring effects of clay content and mineralogy, cation chemistry, and other factors. The differences in aggregate behavior are likely to be relevant to transport and deposition of sediment eroded from these soils, and possibly to the transport of OM or nutrients with eroded soil. We hope to incorporate this method into ongoing field studies of soil erosion with colleagues at UW-Madison.

Stability of Child Behavioral Style in the First 30 Months of Life: Single Timepoint and Aggregated Measures

ERIC Educational Resources Information Center

Parade, Stephanie H.; Dickstein, Susan; Schiller, Masha; Hayden, Lisa; Seifer, Ronald

2015-01-01

The current study examined the stability of temperament over time. Observers and mothers rated child behavior at eight timepoints across three assessment waves (8, 15, and 30 months of age). Internal consistency reliability of aggregates of the eight observer reports and eight mother reports were high. When considering single timepoint…

[Study on the aggregation behavior of cationic porphyrins and their interaction with ctDNA].

PubMed

Ma, Hong-Min; Chen, Xin; Sun, Shu-Ting; Zhang, Li-Na; Wu, Dan; Zhu, Pei-Hua; Li, Yan; Du, Bin; Wei, Qin

2009-02-01

Interest in the interaction between cationic porphyrins, particularly derivatives of meso-tetra(N-methylpyridinium-4-yl) porphyrin(TMPyP), and DNA abounds because they are versatile DNA-binding agents that could find application in photodynamic therapy, cancer detection, artificial nucleases, virus inhibition and so on. The interaction of two water-soluble cationic porphyrins, meso-tetrakis(4-N, N, N-trimethylanilinium) porphyrin (TMAP) and 5-phenyl-10,15,20-tris[4-(N-methyl) pyridinium]porphyrin (TriMPyP), with calf thymus DNA (ctDNA) was studied by UV-Vis absorption spectroscopy, fluorescence spectroscopy and resonance light scattering technique. TriMPyP forms aggregate in water due to the molecular asymmetry while TMAP exists as monomers. At lower concentrations of ctDNA (R > 1, R = c(TMAP)/c(DNA) base pair), the interaction of TMAP with DNA leads to significant hypochromicity and bathochromic shift of absorption spectra. And the fluorescence of TMAP was quenched while it showed enhanced resonance light scattering signals. But the extent of enhancement of resonance light scattering signals is very small, so the aggregate of TMAP is not very high. These observations indicate the self-stacking of TMAP along the DNA surface. At higher concentrations of ctDNA (R < 1), TMAP association with DNA is via outside binding which is accompanied with hyperchromic effect and fluorescence enhancement while the resonance light scattering signals is reduced. DNA addition decreases the fluorescence intensity of TriMPyP and it shifts the peak to the higher wavelengths (red shift). The interaction with DNA promotes the aggregation of TriMPyP and no simple outside binding is observed even at higher concentrations of ctDNA. The steric effect of molecular distortion constrains the intercalation or further binding to DNA. The effect of ionic strength on the interaction was investigated at two DNA concentrations, 1.2 and 24.0 micromol x L(-1), for TMAP. The Interactions of both porphyrins with DNA show high sensitivity to ionic strength. By addition of NaCl, electrostatic attraction is decreased, resulting in the change of binding mode.

Molecular dynamics simulations on networks of heparin and collagen.

PubMed

Kulke, Martin; Geist, Norman; Friedrichs, Wenke; Langel, Walter

2017-06-01

Synthetic scaffolds containing collagen (Type I) are of increasing interest for bone tissue engineering, especially for highly porous biomaterials in combination with glycosaminoglycans. In experiments the integration of heparin during the fibrillogenesis resulted in different types of collagen fibrils, but models for this aggregation on a molecular scale were only tentative. We conducted molecular dynamic simulations investigating the binding of heparin to collagen and the influence of the telopeptides during collagen aggregation. This aims at explaining experimental findings on a molecular level. Novel structures for N- and C-telopeptides were developed with the TIGER2 replica exchange algorithm and dihedral principle component analysis. We present an extended statistical analysis of the mainly electrostatic interaction between heparin and collagen and identify several binding sites. Finally, we propose a molecular mechanism for the influence of glycosaminoglycans on the morphology of collagen fibrils. Proteins 2017; 85:1119-1130. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Thermoregulation and aggregation in neonatal bearded dragons (Pogona vitticeps).

PubMed

Khan, Jameel J; Richardson, Jean M L; Tattersall, Glenn J

2010-05-11

Ectothermic vertebrates, such as reptiles, thermoregulate behaviorally by choosing from available temperatures in their environment. As neonates, bearded dragons (Pogona vitticeps) are often observed to aggregate in vertical strata. A proximate mechanism for this behavior is the thermal advantage of heat storage (i.e., grouped lizards benefit through a decreased surface area to volume ratio), although competition for limited thermal resources, or aggregation for social reasons are alternative explanations. This study was designed to gain an understanding of how aggregation and thermoregulation interact. We observed that both isolated and grouped individuals achieved a similar level of thermoregulation (mean T(b) over trial) within a thermal gradient, but that individuals within a group had lower thermoregulatory precision. An experimental design in which light and ambient temperature (T(a)) (20 versus 30 degrees C) were altered established that a light bulb (source of heat) was a limited and valuable resource to both isolated and grouped neonatal lizards. Lizards aggregated more when the light was on at both temperatures, suggesting that individuals were equally attracted to or repelled from the heat source, depending on the ambient temperature. These data suggest aggregation occurs in neonatal bearded dragons through mutual attraction to a common resource. Further, increased variability in thermal preference occurs in groups, demonstrating the potential for agonistic behaviors to compromise optimal thermoregulation in competitive situations, potentially leading to segregation, rather than aggregation. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.

Molecular dynamics simulations of Aβ fibril interactions with β-sheet breaker peptides.

PubMed

Bruce, Neil J; Chen, Deliang; Dastidar, Shubhra G; Marks, Gabriel E; Schein, Catherine H; Bryce, Richard A

2010-11-01

Accumulation and aggregation of the 42-residue amyloid-β (Aβ) protein fragment, which originates from the cleavage of amyloid precursor protein by β and γ secretase, correlates with the pathology of Alzheimer's disease (AD). Possible therapies for AD include peptides based on the Aβ sequence, and recently identified small molecular weight compounds designed to mimic these, that interfere with the aggregation of Aβ and prevent its toxic effects on neuronal cells in culture. Here, we use molecular dynamics simulations to compare the mode of interaction of an active (LPFFD) and inactive (LHFFD) β-sheet breaker peptide with an Aβ fibril structure from solid-state NMR studies. We found that LHFFD had a weaker interaction with the fibril than the active peptide, LPFFD, from geometric and energetic considerations, as estimated by the MM/PBSA approach. Cluster analysis and computational alanine scanning identified important ligand-fibril contacts, including a possible difference in the effect of histidine on ligand-fibril π-stacking interactions, and the role of the proline residue in establishing contacts that compete with those essential for maintenance of the inter-monomer β-sheet structure of the fibril. Our results show that molecular dynamics simulations can be a useful way to classify the stability of docking sites. These mechanistic insights into the ability of LPFFD to reverse aggregation of toxic Aβ will guide the redesign of lead compounds, and aid in developing realistic therapies for AD and other diseases of protein aggregation. Copyright © 2010 Elsevier Inc. All rights reserved.

Nanoimaging to Prevent and Treat Alzheimer’s and Parkinson’s Diseases. Scientific/Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuri L. Lyubchenko, PhD, DSc

2012-12-20

This project will develop innovative approaches to characterization of the very early stages of protein aggregation that eventually can be translated to the development of early diagnostic tools and efficient treatments for Alzheimer’s, Parkinson’s and Huntington’s diseases. Funding will be used to acquire nanoimaging technology for nanoscale imaging, manipulation and analysis of biomedical materials to develop treatments that will repair disabled proteins and cure diseases that result from protein malfunction, specifically Alzheimer’s and Parkinson’s diseases. Expected outcomes include tests for early diagnosis and therapeutic treatments for these devastating neurological diseases. To elucidate the mechanisms of protein misfolding, we will establishmore » an extensive program of experimental studies using a broad arsenal of advanced nanoscale and traditional techniques that will be integrated with molecular-scale modeling of protein misfolding and the nucleation of aggregate structures. To identify intracellular machinery or/and multicomponent complexes critically involved in protein misfolding, we will characterize interactions between targeted proteins and specific intracellular components or metabolites that impact on protein conformational pathways leading to protein misfolding accompanied by formation of toxic aggregated morphologies. To design innovative nanotechnology tools for the control of intracellular protein misfolding and aggregation processes, we will develop a predictive molecular scale model for intracellular protein misfolding and the formation of toxic aggregates. Verified through experimental studies, the objective is to establish an enabling foundation for the engineering of novel molecular diagnostics and therapeutics for various cellular pathologies.« less

Mechanisms of protein stabilization and prevention of protein aggregation by glycerol.

PubMed

Vagenende, Vincent; Yap, Miranda G S; Trout, Bernhardt L

2009-11-24

The stability of proteins in aqueous solution is routinely enhanced by cosolvents such as glycerol. Glycerol is known to shift the native protein ensemble to more compact states. Glycerol also inhibits protein aggregation during the refolding of many proteins. However, mechanistic insight into protein stabilization and prevention of protein aggregation by glycerol is still lacking. In this study, we derive mechanisms of glycerol-induced protein stabilization by combining the thermodynamic framework of preferential interactions with molecular-level insight into solvent-protein interactions gained from molecular simulations. Contrary to the common conception that preferential hydration of proteins in polyol/water mixtures is determined by the molecular size of the polyol and the surface area of the protein, we present evidence that preferential hydration of proteins in glycerol/water mixtures mainly originates from electrostatic interactions that induce orientations of glycerol molecules at the protein surface such that glycerol is further excluded. These interactions shift the native protein toward more compact conformations. Moreover, glycerol preferentially interacts with large patches of contiguous hydrophobicity where glycerol acts as an amphiphilic interface between the hydrophobic surface and the polar solvent. Accordingly, we propose that glycerol prevents protein aggregation by inhibiting protein unfolding and by stabilizing aggregation-prone intermediates through preferential interactions with hydrophobic surface regions that favor amphiphilic interface orientations of glycerol. These mechanisms agree well with experimental data available in the literature, and we discuss the extent to which these mechanisms apply to other cosolvents, including polyols, arginine, and urea.

An exploration of the relationship between youth assets and engagement in risky sexual behaviors.

PubMed

Evans, Alexandra E; Sanderson, Maureen; Griffin, Sarah F; Reininger, Belinda; Vincent, Murray L; Parra-Medina, Debra; Valois, Robert F; Taylor, Doug

2004-11-01

To examine the relationship between specific youth assets and adolescents' engagement in risky sexual behaviors, as measured by an Aggregate Sexual Risk score, and to specifically explore which youth assets and demographic variables were predictive of youth engagement in risky sexual intercourse. A total of 2108 sexually active high school students attending public high schools in a southern state completed a self-report questionnaire that measured youth assets. Based upon responses to items measuring risk behaviors, an Aggregate Sexual Risk score was calculated for each student. Unconditional logistic regression and multivariate logistic regression analyses were conducted to examine the relationships between the assets and the Aggregate Risk Score. Four separate analyses (white females, white males, black females, and black males) were conducted. In general, the patterns in all four groups indicated that students who had an Aggregate Risk Score of > or = 3 (high risk) possessed less of the measured youth assets. The assets that were most significantly associated with engagement in risky sexual behaviors included self peer values regarding risky behaviors, quantity of other adult support, and youths' empathetic relationships. Thus, students who reported not having these assets were significantly more likely to engage in the risky sexual behaviors. Results underscore the relationship of specific youth assets to sexual risk behaviors. Health researcher and practitioners who work to prevent teen pregnancy and sexually transmitted infections among teenagers need to understand and acknowledge these factors within this population so that the assets can be built or strengthened.

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

DOE PAGES

None, None

2016-03-22

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Molecular chaperone mediated late-stage neuroprotection in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

PubMed

Novoselov, Sergey S; Mustill, Wendy J; Gray, Anna L; Dick, James R; Kanuga, Naheed; Kalmar, Bernadett; Greensmith, Linda; Cheetham, Michael E

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in superoxide dismutase (SOD1) are associated with familial ALS and lead to SOD1 protein misfolding and aggregation. Here we show that the molecular chaperone, HSJ1 (DNAJB2), mutations in which cause distal hereditary motor neuropathy, can reduce mutant SOD1 aggregation and improve motor neuron survival in mutant SOD1 models of ALS. Overexpression of human HSJ1a (hHSJ1a) in vivo in motor neurons of SOD1(G93A) transgenic mice ameliorated disease. In particular, there was a significant improvement in muscle force, increased motor unit number and enhanced motor neuron survival. hHSJ1a was present in a complex with SOD1(G93A) and led to reduced SOD1 aggregation at late stages of disease progression. We also observed altered ubiquitin immunoreactivity in the double transgenic animals, suggesting that ubiquitin modification might be important for the observed improvements. In a cell model of SOD1(G93A) aggregation, HSJ1a preferentially bound to mutant SOD1, enhanced SOD1 ubiquitylation and reduced SOD1 aggregation in a J-domain and ubiquitin interaction motif (UIM) dependent manner. Collectively, the data suggest that HSJ1a acts on mutant SOD1 through a combination of chaperone, co-chaperone and pro-ubiquitylation activity. These results show that targeting SOD1 protein misfolding and aggregation in vivo can be neuroprotective and suggest that manipulation of DnaJ molecular chaperones might be useful in the treatment of ALS.

Insulin aggregation tracked by its intrinsic TRES

NASA Astrophysics Data System (ADS)

Chung, Li Hung C.; Birch, David J. S.; Vyshemirsky, Vladislav; Ryadnov, Maxim G.; Rolinski, Olaf J.

2017-12-01

Time-resolved emission spectra (TRES) have been used to detect conformational changes of intrinsic tyrosines within bovine insulin at a physiological pH. The approach offers the ability to detect the initial stages of insulin aggregation at the molecular level. The data analysis has revealed the existence of at least three fluorescent species undergoing dielectric relaxation and significant spectral changes due to insulin aggregation. The results indicate the suitability of the intrinsic TRES approach for insulin studies and for monitoring its stability during storage and aggregation in insulin delivery devices.

Formation and Growth of Stacking Fault Tetrahedra in Ni via Vacancy Aggregation Mechanism

DOE PAGES

Aidhy, Dilpuneet S.; Lu, Chenyang; Jin, Ke; ...

2015-12-29

Using molecular dynamics simulations, the formation and growth of stacking fault tetrahedra (SFT) are captured by vacancy cluster diffusion and aggregation mechanisms in Ni. The vacancytetrahedron acts as a nucleation point for SFT formation. Simulations show that perfect SFT can grow to the next size perfect SFT via a vacancy aggregation mechanism. The stopping and range of ions in matter (SRIM) calculations and transmission electron microscopy (TEM) observations reveal that SFT can form farther away from the initial cascade-event locations, indicating the operation of diffusion-based vacancy-aggregation mechanism.

Formation and Growth of Stacking Fault Tetrahedra in Ni via Vacancy Aggregation Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aidhy, Dilpuneet S.; Lu, Chenyang; Jin, Ke

Using molecular dynamics simulations, the formation and growth of stacking fault tetrahedra (SFT) are captured by vacancy cluster diffusion and aggregation mechanisms in Ni. The vacancytetrahedron acts as a nucleation point for SFT formation. Simulations show that perfect SFT can grow to the next size perfect SFT via a vacancy aggregation mechanism. The stopping and range of ions in matter (SRIM) calculations and transmission electron microscopy (TEM) observations reveal that SFT can form farther away from the initial cascade-event locations, indicating the operation of diffusion-based vacancy-aggregation mechanism.

Kinetic Behavior of Exchange-Driven Growth with Catalyzed-Birth Processes

NASA Astrophysics Data System (ADS)

Wang, Hai-Feng; Lin, Zhen-Quan; Kong, Xiang-Mu

2006-12-01

Two catalyzed-birth models of n-species (n>=2) aggregates with exchange-driven growth processes are proposed and compared. In the first one, the exchange reaction occurs between any two aggregates Amk and Amj of the same species with the rate kernels Km(k,j) = Kmkj (m = 1,2,...,n, n>=2), and aggregates of An species catalyze a monomer-birth of Al species (l = 1,2,...,n-1) with the catalysis rate kernel Jl(k,j) = Jlkjυ. The kinetic behaviors are investigated by means of the mean-field theory. We find that the evolution behavior of aggregate-size distribution alk(t) of Al species depends crucially on the value of the catalysis rate parameter υ: (i) alk(t) obeys the conventional scaling law in the case of υ<=0, (ii) alk(t) satisfies a modified scaling form in the case of υ>0. In the second model, the mechanism of monomer-birth of An-species catalyzed by Al species is added on the basis of the first model, that is, the aggregates of Al and An species catalyze each other to cause monomer-birth. The kinetic behaviors of Al and An species are found to fall into two categories for the different υ: (i) growth obeying conventional scaling form with υ<=0, (ii) gelling at finite time with υ>0.

Aggregation Pheromone System: A Real-parameter Optimization Algorithm using Aggregation Pheromones as the Base Metaphor

NASA Astrophysics Data System (ADS)

Tsutsui, Shigeyosi

This paper proposes an aggregation pheromone system (APS) for solving real-parameter optimization problems using the collective behavior of individuals which communicate using aggregation pheromones. APS was tested on several test functions used in evolutionary computation. The results showed APS could solve real-parameter optimization problems fairly well. The sensitivity analysis of control parameters of APS is also studied.

Vibronic singlet and triplet steady-state interplay emissions in phenazine-based 1,2,3-triazole films

NASA Astrophysics Data System (ADS)

Costa, Bárbara B. A.; Souza, Paula D. C.; Gontijo, Rafael N.; Jardim, Guilherme A. M.; Moreira, Roberto L.; da Silva, Eufrânio N.; Cury, Luiz A.

2018-03-01

Photoluminescence and phosphorescence emissions of solid-state phenazine films were investigated in steady-state experimental conditions. Important discrepancies were observed for blended films where a host optically inert matrix was introduced to disperse the probe molecules. A vibronic spin-orbit phosphorescent emission clearly appeared, while for the films solely composed by the probe molecules, the phosphorescence broadened and presented a structureless shape, shifted to longer wavelengths. Further Arrhenius behavior analysis on the photoluminescent and phosphorescent emissions on temperature, corroborated the direct and reverse intersystem crossing interplay between singlet and triplet states. Molecular aggregation is responsible for the deterioration of non-blended triazole films phosphorescence.

Polyelectrolyte bundles

NASA Astrophysics Data System (ADS)

Limbach, H. J.; Sayar, M.; Holm, C.

2004-06-01

Using extensive Molecular Dynamics simulations we study the behavior of polyelectrolytes with hydrophobic side chains, which are known to form cylindrical micelles in aqueous solution. We investigate the stability of such bundles with respect to hydrophobicity, the strength of the electrostatic interaction, and the bundle size. We show that for the parameter range relevant for sulfonated poly-para-phenylenes (PPP) one finds a stable finite bundle size. In a more generic model we also show the influence of the length of the precursor oligomer on the stability of the bundles. We also point out that our model has close similarities to DNA solutions with added condensing agents, hinting to the possibility that the size of DNA aggregates is under certain circumstances thermodynamically limited.

Phase Acrobatics: The Influence of Excitonic Resonance and Gold Nonresonant Background on Heterodyne-Detected Vibrational Sum Frequency Generation Emission.

PubMed

Rich, Christopher C; Lindberg, Kathryn A; Krummel, Amber T

2017-04-06

We show how heterodyne-detected vibrational sum frequency generation (HD-VSFG) spectroscopy can discriminate between the excitonic and monomeric properties of a helical, nanotube molecular aggregate by monitoring the phase of the VSFG emission associated with different polarization configurations. By keeping track of the "phase acrobatics" associated with the added phase of the nonresonant SFG emission of gold as well as that of the double-resonance conditions achieved when the SF frequency is resonant with an electronic exciton transition, we discover that for aggregates of tetra(sulfonatophenyl)porphyrin (TSPP) the PPP-polarized spectra exhibit double-resonance conditions while SSP-polarized spectra exhibit resonance only with the ground-state vibration. Along with observed shifts in the vibrational frequency, intensity differences, and sign flips in the imaginary second-order susceptibility, χ s,Im (2) , we conclude that PPP-polarized HD-VSFG spectra reflect the delocalized, excitonic nature of the molecular aggregate, while the SSP-polarized HD-VSFG spectra measure the localized, monomeric nature of the molecular subunits. It is implied from this study that HD-VSFG spectroscopy can be uniquely utilized to measure the excitonic and monomeric properties associated with molecular assemblies for a single sample.

Effects of lightweight fly ash aggregate properties on the behavior of lightweight concretes.

PubMed

Kockal, Niyazi Ugur; Ozturan, Turan

2010-07-15

Influence of different lightweight fly ash aggregates on the behavior of concrete mixtures was discussed. The performance characteristics of lightweight concretes (LWCs) and normalweight concrete (NWC) were investigated through compressive strength, modulus of elasticity and splitting tensile strength representing the mechanical behavior; through rapid chloride permeability representing the transport properties and through rapid freezing and thawing cycling representing the durability of concrete. In order to investigate the aggregate-cement paste interfacial transition zone (ITZ), SEM observations were performed. Regression and graphical analysis of the experimental data obtained were also performed. An increase in compressive strength was observed with the increase in oven-dry density. The ratios of splitting tensile strength to compressive strength of lightweight aggregate concretes were found to be similar to that of normalweight concrete. All the 28- and 56-day concrete specimens had a durability factor greater than 85 and 90, respectively, which met the requirement for freezing and thawing durability. 2010 Elsevier B.V. All rights reserved.

Sodium effect on self-organization of amphiphilic carboxylates: formation of structured micelles and superlattices.

PubMed

Rosenlehner, Karin; Schade, Boris; Böttcher, Christoph; Jäger, Christof M; Clark, Timothy; Heinemann, Frank W; Hirsch, Andreas

2010-08-16

Not only the self-aggregation of dendritic polycarboxylates into structurally persistent micelles, but also that of the micelles themselves into superlattices is controlled by alkali-metal counterions and shows a pronounced sodium effect. Our combined experimental and computational work has revealed the formation of superlattices for the first time. The behavior of a variety of amphiphilic carboxylates and the different effects of the alkali cations Li(+), Na(+), and K(+) have been investigated by conductivity measurements, cryogenic transmission electron microscopy (cryo-TEM), and molecular-dynamics (MD) simulations. Together, these show that sodium salts of the amphiphiles give the most stable micelles, followed by lithium and potassium. Our results suggest that ion multiplets in bridging positions, rather than contact ion pairs, are responsible for the enhanced stability and the formation of hexagonally ordered superlattices with sodium counterions. Potassium ions do not form such ion multiplets and cannot therefore induce aggregation of the micelles. This sodium effect has far-reaching consequences for a large number of biological and technical systems and sheds new light on the origin of specific-ion effects.

Improved Accuracy of Low Affinity Protein-Ligand Equilibrium Dissociation Constants Directly Determined by Electrospray Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Jaquillard, Lucie; Saab, Fabienne; Schoentgen, Françoise; Cadene, Martine

2012-05-01

There is continued interest in the determination by ESI-MS of equilibrium dissociation constants (KD) that accurately reflect the affinity of a protein-ligand complex in solution. Issues in the measurement of KD are compounded in the case of low affinity complexes. Here we present a KD measurement method and corresponding mathematical model dealing with both gas-phase dissociation (GPD) and aggregation. To this end, a rational mathematical correction of GPD (fsat) is combined with the development of an experimental protocol to deal with gas-phase aggregation. A guide to apply the method to noncovalent protein-ligand systems according to their kinetic behavior is provided. The approach is validated by comparing the KD values determined by this method with in-solution KD literature values. The influence of the type of molecular interactions and instrumental setup on fsat is examined as a first step towards a fine dissection of factors affecting GPD. The method can be reliably applied to a wide array of low affinity systems without the need for a reference ligand or protein.

Alzheimer’s disease: biological aspects, therapeutic perspectives and diagnostic tools

NASA Astrophysics Data System (ADS)

Di Carlo, M.; Giacomazza, D.; San Biagio, P. L.

2012-06-01

Alzheimer’s disease (AD) is the most common form of dementia among older people. Dementia is an irreversible brain disorder that seriously affects a person’s ability to carry out daily activities. It is characterized by loss of cognitive functioning and behavioral abilities, to such an extent that it interferes with the daily life and activities of the affected patients. Although it is still unknown how the disease process begins, it seems that brain damage starts a decade or more before problems become evident. Scientific data seem to indicate that changes in the generation or the degradation of the amyloid-b peptide (Aβ) lead to the formation of aggregated structures that are the triggering molecular events in the pathogenic cascade of AD. This review summarizes some characteristic features of Aβ misfolding and aggregation and how cell damage and death mechanisms are induced by these supramolecular and toxic structures. Further, some interventions for the early diagnosis of AD are described and in the last part the potential therapeutic strategies adoptable to slow down, or better block, the progression of the pathology are reported.

Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase

PubMed Central

Babaoglu, Kerim; Simeonov, Anton; Irwin, John J.; Nelson, Michael E.; Feng, Brian; Thomas, Craig J.; Cancian, Laura; Costi, M. Paola; Maltby, David A.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.; Shoichet, Brian K.

2009-01-01

High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate “hit lists”; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against β-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting β-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 µM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. PMID:18333608

Molecular assembly and magnetic dynamics of two novel Dy6 and Dy8 aggregates.

PubMed

Guo, Yun-Nan; Chen, Xiao-Hua; Xue, Shufang; Tang, Jinkui

2012-04-02

Complexation of dysprosium(III) with the heterodonor chelating ligand o-vanillin picolinoylhydrazone (H(2)ovph) in the presence of a carbonato ligand affords two novel Dy(6) and Dy(8) clusters, namely, [Dy(6)(ovph)(4)(Hpvph)(2)Cl(4)(H(2)O)(2)(CO(3))(2)]·CH(3)OH·H(2)O·CH(3)CN (2) and [Dy(8)(ovph)(8)(CO(3))(4)(H(2)O)(8)]·12CH(3)CN·6H(2)O (3). Compound 2 is composed of three petals of the Dy(2) units linked by two carbonato ligands, forming a triangular prism arrangement, while compound 3 possesses an octanuclear core with an unprecedented tub conformation, in which Dy(ovph) fragments are attached to the sides of the carbonato core. The static and dynamic magnetic properties are reported and discussed. In the Dy(6) aggregate, three Dy(2) "skeletons", having been well preserved (see the scheme), contribute to the single-molecule-magnet behavior with a relatively slow tunneling rate, while the Dy(8) cluster only exhibits a rather small relaxation barrier.

A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

PubMed

Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

2016-03-14

The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

The saliva proteome of the blood-feeding insect Triatoma infestans is rich in platelet-aggregation inhibitors

NASA Astrophysics Data System (ADS)

Charneau, Sébastien; Junqueira, Magno; Costa, Camila M.; Pires, Daniele L.; Fernandes, Ellen S.; Bussacos, Ana C.; Sousa, Marcelo V.; Ricart, Carlos André O.; Shevchenko, Andrej; Teixeira, Antonio R. L.

2007-12-01

The saliva of the bloodsucking bug Triatoma infestans vector of Chagas disease contains an anti-hemostatic molecular cocktail that prevents coagulation, vasoconstriction and platelet aggregation in a vertebrate prey. In order to characterize T. infestans saliva proteome, we separated the secreted saliva by two-dimensional gel electrophoresis (2-DE). More than 200 salivary proteins were detected on the 2-DE map, mainly in the alkaline region. By nanoLC-MS/MS analysis using a LTQ-Orbitrap equipment followed by a combination of conventional and sequence-similarity searches, we identified 58 main protein spots. Most of such proteins possess potential blood-feeding associated functions, particularly anti-platelet aggregation proteins belonging to lipocalin and apyrase families. The saliva protein composition indicates a highly specific molecular mechanism of early response to platelet aggregation. This first proteome analysis of the T. infestans secreted saliva provides a basis for a better understanding of this fluid protein composition highly directed to counterpart hemostasis of the prey, thus promoting the bug's blood-feeding.

Cellulose Aggregation under Hydrothermal Pretreatment Conditions.

PubMed

Silveira, Rodrigo L; Stoyanov, Stanislav R; Kovalenko, Andriy; Skaf, Munir S

2016-08-08

Cellulose, the most abundant biopolymer on Earth, represents a resource for sustainable production of biofuels. Thermochemical treatments make lignocellulosic biomaterials more amenable to depolymerization by exposing cellulose microfibrils to enzymatic or chemical attacks. In such treatments, the solvent plays fundamental roles in biomass modification, but the molecular events underlying these changes are still poorly understood. Here, the 3D-RISM-KH molecular theory of solvation has been employed to analyze the role of water in cellulose aggregation under different thermodynamic conditions. The results show that, under ambient conditions, highly structured hydration shells around cellulose create repulsive forces that protect cellulose microfibrils from aggregating. Under hydrothermal pretreatment conditions, however, the hydration shells lose structure, and cellulose aggregation is favored. These effects are largely due to a decrease in cellulose-water interactions relative to those at ambient conditions, so that cellulose-cellulose attractive interactions become prevalent. Our results provide an explanation to the observed increase in the lateral size of cellulose crystallites when biomass is subject to pretreatments and deepen the current understanding of the mechanisms of biomass modification.

Iodine bonding stabilizes iodomethane in MIDAS pesticide. Theoretical study of intermolecular interactions between iodomethane and chloropicrin.

PubMed

Glaser, Rainer; Prugger, Kaitlan

2012-02-22

The results are reported of a theoretical study of iodomethane (H(3)C-I, 1) and chloropicrin (Cl(3)C-NO(2), 2), of the heterodimers 3-6 formed by aggregation of 1 and 2, and of their addition products 7 and 8 and their possible fragmentation reactions to 9-18. Mixtures of iodomethane and chloropicrin are not expected to show chemistry resulting from their reactions with each other. The structures and stabilities are discussed of the iodine-bonded molecular aggregates (IBMA) 3 and 4 and of the hydrogen- and iodine-bonded molecular aggregates (IHBMA) 5 and 6. The mixed aggregates 3-5 are bound on the free enthalpy surface relative to the homodimers of 1 and 2, and the IBMA structures 3 and 4 are most stable. This result suggests that the mixture of chloropicrin and iodomethane in the pesticide Midas is a good choice to reduce the volatility of iodomethane because of thermodynamically stabilizing iodine bonding.

Solubilization of poorly soluble photosensitizer hypericin by polymeric micelles and polyethylene glycol.

PubMed

Búzová, Diana; Kasák, Peter; Miškovský, Pavol; Jancura, Daniel

2013-06-01

Hypericin (Hyp) is a promising photosensitizer for photodiagnostic and photodynamic therapy of cancer. However, Hyp has a large conjugated system and in aqueous solutions forms insoluble aggregates which do not possess biological activity. This makes intravenous injection of Hyp problematic and restricts its medical applications. To overcome this problem, Hyp is incorporated into drug delivery systems which can increase its solubility and bioavailability. One of the possibilities is utilization of polymeric micelles. The most used hydrophilic block for preparation of polymeric micelles is polyethylen glycol (PEG). PEG is a polymer which for its lack of immunogenicity, antigenicity and toxicity obtained approval for use in human medicine. In this work we have studied the solubilization of Hyp aggregates in the presence of PEG-PE and PEG-cholesterol micelles. The concentration of polymeric micelles which allows total monomerization of Hyp corresponds to the critical micellar concentration of these micelles (~10(-6) M). We have also investigated the effect of the molecular weight and concentration of PEG on the transition of aggregated Hyp to its monomeric form. PEGs with low molecular weight (< 1000 g/mol) do not significantly contribute to the solubilization of Hyp. However, PEGs with molecular weight > 2000 g/mol efficiently transform Hyp aggregates to the monomeric state of this photosensitizer.

Distribution of Sulfate-Reducing and Methanogenic Bacteria in Anaerobic Aggregates Determined by Microsensor and Molecular Analyses

PubMed Central

Santegoeds, Cecilia M.; Damgaard, Lars Riis; Hesselink, Gijs; Zopfi, Jakob; Lens, Piet; Muyzer, Gerard; de Beer, Dirk

1999-01-01

Using molecular techniques and microsensors for H2S and CH4, we studied the population structure of and the activity distribution in anaerobic aggregates. The aggregates originated from three different types of reactors: a methanogenic reactor, a methanogenic-sulfidogenic reactor, and a sulfidogenic reactor. Microsensor measurements in methanogenic-sulfidogenic aggregates revealed that the activity of sulfate-reducing bacteria (2 to 3 mmol of S2− m−3 s−1 or 2 × 10−9 mmol s−1 per aggregate) was located in a surface layer of 50 to 100 μm thick. The sulfidogenic aggregates contained a wider sulfate-reducing zone (the first 200 to 300 μm from the aggregate surface) with a higher activity (1 to 6 mmol of S2− m−3 s−1 or 7 × 10−9 mol s−1 per aggregate). The methanogenic aggregates did not show significant sulfate-reducing activity. Methanogenic activity in the methanogenic-sulfidogenic aggregates (1 to 2 mmol of CH4 m−3 s−1 or 10−9 mmol s−1 per aggregate) and the methanogenic aggregates (2 to 4 mmol of CH4 m−3 s−1 or 5 × 10−9 mmol s−1 per aggregate) was located more inward, starting at ca. 100 μm from the aggregate surface. The methanogenic activity was not affected by 10 mM sulfate during a 1-day incubation. The sulfidogenic and methanogenic activities were independent of the type of electron donor (acetate, propionate, ethanol, or H2), but the substrates were metabolized in different zones. The localization of the populations corresponded to the microsensor data. A distinct layered structure was found in the methanogenic-sulfidogenic aggregates, with sulfate-reducing bacteria in the outer 50 to 100 μm, methanogens in the inner part, and Eubacteria spp. (partly syntrophic bacteria) filling the gap between sulfate-reducing and methanogenic bacteria. In methanogenic aggregates, few sulfate-reducing bacteria were detected, while methanogens were found in the core. In the sulfidogenic aggregates, sulfate-reducing bacteria were present in the outer 300 μm, and methanogens were distributed over the inner part in clusters with syntrophic bacteria. PMID:10508098

Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability

NASA Astrophysics Data System (ADS)

Camilloni, Carlo; Sala, Benedetta Maria; Sormanni, Pietro; Porcari, Riccardo; Corazza, Alessandra; De Rosa, Matteo; Zanini, Stefano; Barbiroli, Alberto; Esposito, Gennaro; Bolognesi, Martino; Bellotti, Vittorio; Vendruscolo, Michele; Ricagno, Stefano

2016-05-01

A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (β2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G. Our results indicate that W60G low aggregation propensity can be explained, beyond its higher stability, by an increased average protection of the aggregation-prone residues at its surface. To validate these findings, we designed β2m variants that alter the aggregation-prone exposed surface of wild-type and W60G β2m modifying their aggregation propensity. These results allowed us to pinpoint the role of dynamics in β2m aggregation and to provide a new strategy to tune protein aggregation by modulating the exposure of aggregation-prone residues.

Dynamics of proteins aggregation. II. Dynamic scaling in confined media

NASA Astrophysics Data System (ADS)

Zheng, Size; Shing, Katherine S.; Sahimi, Muhammad

2018-03-01

In this paper, the second in a series devoted to molecular modeling of protein aggregation, a mesoscale model of proteins together with extensive discontinuous molecular dynamics simulation is used to study the phenomenon in a confined medium. The medium, as a model of a crowded cellular environment, is represented by a spherical cavity, as well as cylindrical tubes with two aspect ratios. The aggregation process leads to the formation of β sheets and eventually fibrils, whose deposition on biological tissues is believed to be a major factor contributing to many neuro-degenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis diseases. Several important properties of the aggregation process, including dynamic evolution of the total number of the aggregates, the mean aggregate size, and the number of peptides that contribute to the formation of the β sheets, have been computed. We show, similar to the unconfined media studied in Paper I [S. Zheng et al., J. Chem. Phys. 145, 134306 (2016)], that the computed properties follow dynamic scaling, characterized by power laws. The existence of such dynamic scaling in unconfined media was recently confirmed by experiments. The exponents that characterize the power-law dependence on time of the properties of the aggregation process in spherical cavities are shown to agree with those in unbounded fluids at the same protein density, while the exponents for aggregation in the cylindrical tubes exhibit sensitivity to the geometry of the system. The effects of the number of amino acids in the protein, as well as the size of the confined media, have also been studied. Similarities and differences between aggregation in confined and unconfined media are described, including the possibility of no fibril formation, if confinement is severe.

m-Diethynylbenzene macrocycles: syntheses and self-association behavior in solution.

PubMed

Tobe, Yoshito; Utsumi, Naoto; Kawabata, Kazuya; Nagano, Atsushi; Adachi, Kiyomi; Araki, Shunji; Sonoda, Motohiro; Hirose, Keiji; Naemura, Koichiro

2002-05-15

m-Diethynylbenzene macrocycles (DBMs), buta-1,3-diyne-bridged [4(n)]metacyclophanes, have been synthesized and their self-association behaviors in solution were investigated. Cyclic tetramers, hexamers, and octamers of DBMs having exo-annular octyl, hexadecyl, and 3,6,9-trioxadecyl ester groups were prepared by intermolecular oxidative coupling of dimer units or intramolecular cyclization of the corresponding open-chain oligomers. The aggregation properties were investigated by two methods, the (1)H NMR spectra and the vapor pressure osmometry (VPO). Although some discrepancies were observed between the association constants obtained from the two methods, the qualitative view was consistent with each other. The analysis of self-aggregation by VPO revealed unique aggregation behavior of DBMs in acetone and toluene, which was not elucidated by the NMR method. Namely, the association constants for infinite association are several times larger than the dimerization constant, suggesting that the aggregation is enhanced by the formation of dimers (a nucleation mechanism). In polar solvents, DBMs aggregate more strongly than in chloroform due to the solvophobic interactions between the macrocyclic framework and the solvents. Moreover, DBMs self-associate in aromatic solvents such as toluene and o-xylene more readily than in chloroform. In particular, the hexameric DBM having a large macrocyclic cavity exhibits extremely large association constants in aromatic solvents. By comparing the aggregation properties of DBMs with the corresponding acyclic oligomers, the effect of the macrocyclic structure on the aggregation propensity was clarified. Finally, it turned out that DBMs tend to aggregate more readily than the corresponding phenylacetylene macrocycles, acetylene-bridged [2(n)]metacyclophanes, owing to the withdrawal of the electron density from the aromatic rings by the butadiyne linkages which facilitates pi-pi stacking interactions.

Changes in blood aggregation with differences in molecular weight and degree of deacetylation of chitosan.

PubMed

Hattori, Hidemi; Ishihara, Masayuki

2015-01-22

Because the molecular weight (Mw) and degree of deacetylation (DDA) of chitosan can vary depending on the purification method, the identification of appropriate chitosan structures is important for developing more effective hemostatic agents. In this study, the influence of varying Mw and DDA of chitosan on blood aggregation was characterized by 10 types of chitosan with different Mw and DDA, including oligomers. The highest aggregation of whole blood, washed erythrocytes and platelets in platelet-rich plasma (PRP) were observed in chitosan with Mw of 8.6 kDa or more and with DDA of 75 to 88%. However, chitosan with too high Mw (247 kDa) inhibited the aggregation of whole blood, washed erythrocytes and PRP at high chitosan concentration. At certain concentrations, chitosan with 75-85% DDA and 50-190 kDa and chitosan with 87.6% DDA and 247 kDa both aggregated proteins in PRP. Chitosan oligomer did not affect blood aggregation. The results suggested that the aggregation by chitosan depended on the interaction of positively charged chitosan with negatively charged erythrocytes, platelets and plasma protein. It seemed that a suitable balance of positive charge in chitosan and negative charge in hemocytes and some kinds of proteins was important. To develop a hemostatic with effective blood aggregation, the chitosan should not be limited to a single Mw and a single DDA but may be a mixed chitosan with wide range of Mw (8.6-247 kDa) and DDA of 75 to 88%.

Ecological and morphological profile of floating spherical Cladophora socialis aggregations in central Thailand.

PubMed

Tsutsui, Isao; Miyoshi, Tatsuo; Sukchai, Halethichanok; Pinphoo, Piyarat; Aue-Umneoy, Dusit; Meeanan, Chonlada; Songphatkaew, Jaruwan; Klomkling, Sirimas; Yamaguchi, Iori; Ganmanee, Monthon; Sudo, Hiroyuki; Hamano, Kaoru

2015-01-01

The unique beauty of spherical aggregation forming algae has attracted much attention from both the scientific and lay communities. Several aegagropilous seaweeds have been identified to date, including the plants of genus Cladophora and Chaetomorpha. However, this phenomenon remains poorly understood. In July 2013, a mass occurrence of spherical Cladophora aggregations was observed in a salt field reservoir in Central Thailand. The aims of the present study were to describe the habitat of the spherical aggregations and confirm the species. We performed a field survey, internal and external morphological observations, pyrenoid ultrastructure observations, and molecular sequence analysis. Floating spherical Cladophora aggregations (1-8 cm in diameter) were observed in an area ~560 m2, on the downwind side of the reservoir where there was water movement. Individual filaments in the aggregations were entangled in each other; consequently, branches growing in different directions were observed within a clump. We suggest that water movement and morphological characteristics promote the formation of spherical aggregations in this species. The molecular sequencing results revealed that the study species was highly homologous to both C. socialis and C. coelothrix. However, the diameter of the apical cells in the study species was less than that of C. coelothrix. The pyrenoid ultrastructure was more consistent with that of C. socialis. We conclude that the study species is C. socialis. This first record of spherical aggregations in this species advances our understanding of these formations. However, further detailed physical measurements are required to fully elucidate the mechanism behind these spherical formations.

Ecological and Morphological Profile of Floating Spherical Cladophora socialis Aggregations in Central Thailand

PubMed Central

Tsutsui, Isao; Miyoshi, Tatsuo; Sukchai, Halethichanok; Pinphoo, Piyarat; Aue-umneoy, Dusit; Meeanan, Chonlada; Songphatkaew, Jaruwan; Klomkling, Sirimas; Yamaguchi, Iori; Ganmanee, Monthon; Sudo, Hiroyuki; Hamano, Kaoru

2015-01-01

The unique beauty of spherical aggregation forming algae has attracted much attention from both the scientific and lay communities. Several aegagropilous seaweeds have been identified to date, including the plants of genus Cladophora and Chaetomorpha. However, this phenomenon remains poorly understood. In July 2013, a mass occurrence of spherical Cladophora aggregations was observed in a salt field reservoir in Central Thailand. The aims of the present study were to describe the habitat of the spherical aggregations and confirm the species. We performed a field survey, internal and external morphological observations, pyrenoid ultrastructure observations, and molecular sequence analysis. Floating spherical Cladophora aggregations (1–8 cm in diameter) were observed in an area ~560 m2, on the downwind side of the reservoir where there was water movement. Individual filaments in the aggregations were entangled in each other; consequently, branches growing in different directions were observed within a clump. We suggest that water movement and morphological characteristics promote the formation of spherical aggregations in this species. The molecular sequencing results revealed that the study species was highly homologous to both C. socialis and C. coelothrix. However, the diameter of the apical cells in the study species was less than that of C. coelothrix. The pyrenoid ultrastructure was more consistent with that of C. socialis. We conclude that the study species is C. socialis. This first record of spherical aggregations in this species advances our understanding of these formations. However, further detailed physical measurements are required to fully elucidate the mechanism behind these spherical formations. PMID:25898393

Nature of the optical band shapes in polymethine dyes and H-aggregates: dozy chaos and excitons. Comparison with dimers, H*- and J-aggregates.

PubMed

Egorov, Vladimir V

2017-05-01

Results on the theoretical explanation of the shape of optical bands in polymethine dyes, their dimers and aggregates are summarized. The theoretical dependence of the shape of optical bands for the dye monomers in the vinylogous series in line with a change in the solvent polarity is considered. A simple physical (analytical) model of the shape of optical absorption bands in H-aggregates of polymethine dyes is developed based on taking the dozy-chaos dynamics of the transient state and the Frenkel exciton effect in the theory of molecular quantum transitions into account. As an example, the details of the experimental shape of one of the known H-bands are well reproduced by this analytical model under the assumption that the main optical chromophore of H-aggregates is a tetramer resulting from the two most probable processes of inelastic binary collisions in sequence: first, monomers between themselves, and then, between the resulting dimers. The obtained results indicate that in contrast with the compact structure of J-aggregates (brickwork structure), the structure of H-aggregates is not the compact pack-of-cards structure, as stated in the literature, but a loose alternate structure. Based on this theoretical model, a simple general (analytical) method for treating the more complex shapes of optical bands in polymethine dyes in comparison with the H-band under consideration is proposed. This method mirrors the physical process of molecular aggregates forming in liquid solutions: aggregates are generated in the most probable processes of inelastic multiple binary collisions between polymethine species generally differing in complexity. The results obtained are given against a background of the theoretical results on the shape of optical bands in polymethine dyes and their aggregates (dimers, H*- and J-aggregates) previously obtained by V.V.E.

Nature of the optical band shapes in polymethine dyes and H-aggregates: dozy chaos and excitons. Comparison with dimers, H*- and J-aggregates

PubMed Central

2017-01-01

Results on the theoretical explanation of the shape of optical bands in polymethine dyes, their dimers and aggregates are summarized. The theoretical dependence of the shape of optical bands for the dye monomers in the vinylogous series in line with a change in the solvent polarity is considered. A simple physical (analytical) model of the shape of optical absorption bands in H-aggregates of polymethine dyes is developed based on taking the dozy-chaos dynamics of the transient state and the Frenkel exciton effect in the theory of molecular quantum transitions into account. As an example, the details of the experimental shape of one of the known H-bands are well reproduced by this analytical model under the assumption that the main optical chromophore of H-aggregates is a tetramer resulting from the two most probable processes of inelastic binary collisions in sequence: first, monomers between themselves, and then, between the resulting dimers. The obtained results indicate that in contrast with the compact structure of J-aggregates (brickwork structure), the structure of H-aggregates is not the compact pack-of-cards structure, as stated in the literature, but a loose alternate structure. Based on this theoretical model, a simple general (analytical) method for treating the more complex shapes of optical bands in polymethine dyes in comparison with the H-band under consideration is proposed. This method mirrors the physical process of molecular aggregates forming in liquid solutions: aggregates are generated in the most probable processes of inelastic multiple binary collisions between polymethine species generally differing in complexity. The results obtained are given against a background of the theoretical results on the shape of optical bands in polymethine dyes and their aggregates (dimers, H*- and J-aggregates) previously obtained by V.V.E. PMID:28572984

Nature of the optical band shapes in polymethine dyes and H-aggregates: dozy chaos and excitons. Comparison with dimers, H*- and J-aggregates

NASA Astrophysics Data System (ADS)

Egorov, Vladimir V.

2017-05-01

Results on the theoretical explanation of the shape of optical bands in polymethine dyes, their dimers and aggregates are summarized. The theoretical dependence of the shape of optical bands for the dye monomers in the vinylogous series in line with a change in the solvent polarity is considered. A simple physical (analytical) model of the shape of optical absorption bands in H-aggregates of polymethine dyes is developed based on taking the dozy-chaos dynamics of the transient state and the Frenkel exciton effect in the theory of molecular quantum transitions into account. As an example, the details of the experimental shape of one of the known H-bands are well reproduced by this analytical model under the assumption that the main optical chromophore of H-aggregates is a tetramer resulting from the two most probable processes of inelastic binary collisions in sequence: first, monomers between themselves, and then, between the resulting dimers. The obtained results indicate that in contrast with the compact structure of J-aggregates (brickwork structure), the structure of H-aggregates is not the compact pack-of-cards structure, as stated in the literature, but a loose alternate structure. Based on this theoretical model, a simple general (analytical) method for treating the more complex shapes of optical bands in polymethine dyes in comparison with the H-band under consideration is proposed. This method mirrors the physical process of molecular aggregates forming in liquid solutions: aggregates are generated in the most probable processes of inelastic multiple binary collisions between polymethine species generally differing in complexity. The results obtained are given against a background of the theoretical results on the shape of optical bands in polymethine dyes and their aggregates (dimers, H*- and J-aggregates) previously obtained by V.V.E.

Carbon nanotube-templated assembly of regioregular poly(3-alkylthiophene) in solution

NASA Astrophysics Data System (ADS)

Zhu, Jiahua; Stevens, Eric; He, Youjun; Hong, Kunlun; Ivanov, Ilia

2016-09-01

Control of structural heterogeneity by rationally encoding of the molecular assemblies is a key enabling design of hierarchical, multifunctional materials of the future. Here we report the strategies to gain such control using solution- based assembly to construct a hybrid nano-assembly and a network hybrid structure of regioregular poly(3- alkylthiophene) - carbon nanotube (P3AT-CNT). The opto-electronic performance of conjugated polymer (P3AT) is defined by the structure of the aggregate in solution and in the solid film. Control of P3AT aggregation would allow formation of broad range of morphologies with very distinct electro-optical. We utilize interactive templating to confine the assembly behavior of conjugated polymers, replacing poorly controlled solution processing approach. Perfect crystalline surface of the single-walled and multi-walled carbon nanotube (SWCNT/MWCNT) acts as a template, seeding P3AT aggregation of the surface of the nanotube. The seed continues directional growth through pi-pi stacking leading to the formation of to well-defined P3AT-CNT morphologies, including comb-like nano-assemblies, super- structures and gel networks. Interconnected, highly-branched network structure of P3AT-CNT hybrids is of particular interest to enable efficient, long-range, balanced charge carrier transport. The structure and opto-electionic function of the intermediate assemblies and networks of P3AT/CNT hybrids are characterized by transmission election microscopy and UV-vis absorption.

Simulation Studies of LCST-like Phase Transitions in Elastin-like Polypeptides (ELPs) and Conjugates of ELP with Rigid Macromolecules

NASA Astrophysics Data System (ADS)

Condon, Joshua; Martin, Tyler; Jayaraman, Arthi

We use atomistic (AA) and coarse-grained (CG) molecular dynamics simulations to elucidate the thermodynamic driving forces governing lower critical solution temperature (LCST)-like phase transition exhibited by elastin-like peptides (ELPs) and conjugates of ELP with other macromolecules. In the AA simulations, we study ELP oligomers in explicit water, and mark the transition as the temperature at which they undergo a change in ``hydration'' state. While AA simulations are restricted to small systems of short ELPs and do not capture the chain aggregation observed in experiments of ELPs, they guide the phenomenological CG model development by highlighting the solvent induced polymer-polymer effective interactions with changing temperature. In the CG simulations, we capture the LCST polymer aggregation by increasing polymer-polymer effective attractive interactions in an implicit solvent. We examine the impact of conjugating a block of LCST polymer to another rigid unresponsive macromolecular block on the LCST-like transition. We find that when multiple LCST polymers are conjugated to a rigid polymer block, increased crowding of the LCST polymers shifts the onset of chain aggregation to smaller effective polymer-polymer attraction compared to the free LCST polymers. These simulation results provide guidance on the design of conjugated bio-mimetic thermoresponsive materials, and shape the fundamental understanding of the impact of polymer crowding on phase behavior in thermoresponsive LCST polymer systems.

Barnacle cement: a polymerization model based on evolutionary concepts

PubMed Central

Dickinson, Gary H.; Vega, Irving E.; Wahl, Kathryn J.; Orihuela, Beatriz; Beyley, Veronica; Rodriguez, Eva N.; Everett, Richard K.; Bonaventura, Joseph; Rittschof, Daniel

2009-01-01

Summary Enzymes and biochemical mechanisms essential to survival are under extreme selective pressure and are highly conserved through evolutionary time. We applied this evolutionary concept to barnacle cement polymerization, a process critical to barnacle fitness that involves aggregation and cross-linking of proteins. The biochemical mechanisms of cement polymerization remain largely unknown. We hypothesized that this process is biochemically similar to blood clotting, a critical physiological response that is also based on aggregation and cross-linking of proteins. Like key elements of vertebrate and invertebrate blood clotting, barnacle cement polymerization was shown to involve proteolytic activation of enzymes and structural precursors, transglutaminase cross-linking and assembly of fibrous proteins. Proteolytic activation of structural proteins maximizes the potential for bonding interactions with other proteins and with the surface. Transglutaminase cross-linking reinforces cement integrity. Remarkably, epitopes and sequences homologous to bovine trypsin and human transglutaminase were identified in barnacle cement with tandem mass spectrometry and/or western blotting. Akin to blood clotting, the peptides generated during proteolytic activation functioned as signal molecules, linking a molecular level event (protein aggregation) to a behavioral response (barnacle larval settlement). Our results draw attention to a highly conserved protein polymerization mechanism and shed light on a long-standing biochemical puzzle. We suggest that barnacle cement polymerization is a specialized form of wound healing. The polymerization mechanism common between barnacle cement and blood may be a theme for many marine animal glues. PMID:19837892

Aggregation of Aß(25-35) on DOPC and DOPC/DHA bilayers: an atomic force microscopy study.

PubMed

Sublimi Saponetti, Matilde; Grimaldi, Manuela; Scrima, Mario; Albonetti, Cristiano; Nori, Stefania Lucia; Cucolo, Annamaria; Bobba, Fabrizio; D'Ursi, Anna Maria

2014-01-01

β amyloid peptide plays an important role in both the manifestation and progression of Alzheimer disease. It has a tendency to aggregate, forming low-molecular weight soluble oligomers, higher-molecular weight protofibrillar oligomers and insoluble fibrils. The relative importance of these single oligomeric-polymeric species, in relation to the morbidity of the disease, is currently being debated. Here we present an Atomic Force Microscopy (AFM) study of Aβ(25-35) aggregation on hydrophobic dioleoylphosphatidylcholine (DOPC) and DOPC/docosahexaenoic 22∶6 acid (DHA) lipid bilayers. Aβ(25-35) is the smallest fragment retaining the biological activity of the full-length peptide, whereas DOPC and DOPC/DHA lipid bilayers were selected as models of cell-membrane environments characterized by different fluidity. Our results provide evidence that in hydrophobic DOPC and DOPC/DHA lipid bilayers, Aβ(25-35) forms layered aggregates composed of mainly annular structures. The mutual interaction between annular structures and lipid surfaces end-results into a membrane solubilization. The presence of DHA as a membrane-fluidizing agent is essential to protect the membrane from damage caused by interactions with peptide aggregates; to reduces the bilayer defects where the delipidation process starts.

Study of aggregative behavior of Rhinophrynus dorsalis tadpoles: design and analysis

USGS Publications Warehouse

Foster, M.S.; McDiarmid, R.W.

1982-01-01

We conducted experiments using the apparatus and design followed by Wassersug and Hessler (1971) and Wassersug (1973) to test the aggregative behavior of tadpoles of Rhinophrynus dorsalis in response to visual and olfactory stimuli. Results neither supported nor refuted the hypothesis that either stimulus is used as a mechanism for school formation. The exercise did lead to doubts about the experimental design. Some ambiguity resulted from the fact that the significance of the results depended upon the way in which the data were analyzed. Several alternative methods were considered. We also observed tadpoles reared in isolation to determine the effect of prior social conditioning on aggregative behavior. Isolates grew less than group-reared animals, were less active, and exhibited a strong avoidance reaction when subsequently exposed to conspecifics.

A critical-like collective state leads to long-range cell communication in Dictyostelium discoideum aggregation

PubMed Central

De Palo, Giovanna; Yi, Darvin; Endres, Robert G.

2017-01-01

The transition from single-cell to multicellular behavior is important in early development but rarely studied. The starvation-induced aggregation of the social amoeba Dictyostelium discoideum into a multicellular slug is known to result from single-cell chemotaxis towards emitted pulses of cyclic adenosine monophosphate (cAMP). However, how exactly do transient, short-range chemical gradients lead to coherent collective movement at a macroscopic scale? Here, we developed a multiscale model verified by quantitative microscopy to describe behaviors ranging widely from chemotaxis and excitability of individual cells to aggregation of thousands of cells. To better understand the mechanism of long-range cell—cell communication and hence aggregation, we analyzed cell—cell correlations, showing evidence of self-organization at the onset of aggregation (as opposed to following a leader cell). Surprisingly, cell collectives, despite their finite size, show features of criticality known from phase transitions in physical systems. By comparing wild-type and mutant cells with impaired aggregation, we found the longest cell—cell communication distance in wild-type cells, suggesting that criticality provides an adaptive advantage and optimally sized aggregates for the dispersal of spores. PMID:28422986

Molecular description of the LCST behavior of an elastin-like polypeptide.

PubMed

Li, Nan K; García Quiroz, Felipe; Hall, Carol K; Chilkoti, Ashutosh; Yingling, Yaroslava G

2014-10-13

Elastin-like polypeptides (ELPs) with the repeat sequence of VPGVG are widely used as a model system for investigation of lower critical solution temperature (LCST) transition behavior. In this paper, the effect of temperature on the structure, dynamics and association of (VPGVG)18 in aqueous solution is investigated using atomistic molecular dynamics simulations. Our simulations show that as the temperature increases the ELP backbones undergo gradual conformational changes, which are attributed to the formation of more ordered secondary structures such as β-strands. In addition, increasing temperature changes the hydrophobicity of the ELP by exposure of hydrophobic valine-side chains to the solvent and hiding of proline residues. Based on our simulations, we conclude that the transition behavior of (VPGVG)18 can be attributed to a combination of thermal disruption of the water network that surrounds the polypeptide, reduction of solvent accessible surface area of the polypeptide, and increase in its hydrophobicity. Simulations of the association of two (VPGVG)18 molecules demonstrated that the observed gradual changes in the structural properties of the single polypeptide chain are enough to cause the aggregation of polypeptides above the LCST. These results lead us to propose that the LCST phase behavior of poly(VPGVG) is a collective phenomenon that originates from the correlated gradual changes in single polypeptide structure and the abrupt change in properties of hydration water around the peptide and is a result of a competition between peptide-peptide and peptide-water interactions. This is a computational study of an important intrinsically disordered peptide system that provides an atomic-level description of structural features and interactions that are relevant in the LCST phase behavior.

Study of the structural role of gallium and aluminum in 45S5 bioactive glasses by molecular dynamics simulations.

PubMed

Malavasi, Gianluca; Pedone, Alfonso; Menziani, Maria Cristina

2013-04-18

The structural properties of phosphosilicate glasses based on the 45S5 Bioglass doped with gallium and aluminum (46.2 SiO2·24.3Na2O·26.9CaO·2.6P2O5·1.0X2O3, X = Ga or Al) are investigated by means of classical molecular dynamics simulations. Structural features of the two compositions are compared with those of the original 45S5 Bioglass in order to relate them to the different known bioactivities of these materials. Differences in the coordination environments of Ga and Al, network connectivity, and ion aggregation reveal a microscopic model of these glasses which supports the interpretation of the experimental data and provides new insight into the different biological behaviors of Ga- and Al-containing phosphosilicate glasses. Although Ga is found predominantly in a 4-fold coordination environment, small amounts of 5- and 6-fold coordinated atoms have been detected depending on the interatomic potential model employed. This suggests its possible intermediate role in phosphosilicate glasses. On the contrary, Al plays a network former role and leads to glasses with a more polymerized structure. Interestingly, the results show an increased propensity for aggregation of the Ca(2+) and PO4(3-) ions in the Al-containing phosphosilicate glasses with respect to the Ga-containing ones. This leads to insoluble calcium-phosphate-rich regions not detected in the bioactive glasses.

Bistable aggregate of all-trans-astaxanthin in an aqueous solution

NASA Astrophysics Data System (ADS)

Mori, Yuso; Yamano, Kuniko; Hashimoto, Hideki

1996-05-01

The temperature dependence of the optical absorption spectra for astaxanthin aggregate has been studied between 2 and 32°C. Red-shifted absorption bands as compared to the monomer absorption band are found above 21°C in addition to the blue-shifted band of the aggregate. The spectra suggest that the molecular arrangement in the aggregate is a bistable one consisting of head-to-tail and card-packed arrangements. A diagram describing the bistability together with the monomer state is proposed in the space defined by the free energy and the quantity of Σi = 1 N< θ12 + < σθ12 for the ith molecule in the N-molecule aggregate.

Molecular modeling the microstructure and phase behavior of bulk and inhomogeneous complex fluids

NASA Astrophysics Data System (ADS)

Bymaster, Adam

Accurate prediction of the thermodynamics and microstructure of complex fluids is contingent upon a model's ability to capture the molecular architecture and the specific intermolecular and intramolecular interactions that govern fluid behavior. This dissertation makes key contributions to improving the understanding and molecular modeling of complex bulk and inhomogeneous fluids, with an emphasis on associating and macromolecular molecules (water, hydrocarbons, polymers, surfactants, and colloids). Such developments apply broadly to fields ranging from biology and medicine, to high performance soft materials and energy. In the bulk, the perturbed-chain statistical associating fluid theory (PC-SAFT), an equation of state based on Wertheim's thermodynamic perturbation theory (TPT1), is extended to include a crossover correction that significantly improves the predicted phase behavior in the critical region. In addition, PC-SAFT is used to investigate the vapor-liquid equilibrium of sour gas mixtures, to improve the understanding of mercaptan/sulfide removal via gas treating. For inhomogeneous fluids, a density functional theory (DFT) based on TPT1 is extended to problems that exhibit radially symmetric inhomogeneities. First, the influence of model solutes on the structure and interfacial properties of water are investigated. The DFT successfully describes the hydrophobic phenomena on microscopic and macroscopic length scales, capturing structural changes as a function of solute size and temperature. The DFT is used to investigate the structure and effective forces in nonadsorbing polymer-colloid mixtures. A comprehensive study is conducted characterizing the role of polymer concentration and particle/polymer size ratio on the structure, polymer induced depletion forces, and tendency towards colloidal aggregation. The inhomogeneous form of the association functional is used, for the first time, to extend the DFT to associating polymer systems, applicable to any association scheme. Theoretical results elucidate how reversible bonding governs the structure of a fluid near a surface and in confined environments, the molecular connectivity (formation of supramolecules, star polymers, etc.) and the phase behavior of the system. Finally, the DFT is extended to predict the inter- and intramolecular correlation functions of polymeric fluids. A theory capable of providing such local structure is important to understanding how local chemistry, branching, and bond flexibility affect the thermodynamic properties of polymers.

Synthesis, Photophysical Characterization, and Gelation Studies of a Stilbene-Cholesterol Derivative

ERIC Educational Resources Information Center

Geiger, H. Christina; Geiger, David K.; Baldwin, Christine

2006-01-01

Organogels are low molar mass organic compounds with the ability to immobilize an incredible quantity of solvent and fibrous aggregation of these compounds formed by noncovalent interaction usually involves hydrogen bonding. For stilbene-cholesterol based gelators, the driving force for molecular aggregation are weak van der Waal interactions…

Bovine insulin-phosphatidylcholine mixed Langmuir monolayers: behavior at the air-water interface.

PubMed

Pérez-López, S; Blanco-Vila, N M; Vila-Romeu, N

2011-08-04

The behavior of the binary mixed Langmuir monolayers of bovine insulin (INS) and phosphatidylcholine (PC) spread at the air-water interface was investigated under various subphase conditions. Pure and mixed monolayers were spread on water, on NaOH and phosphate-buffered solutions of pH 7.4, and on Zn(2+)-containing solutions. Miscibility and interactions between the components were studied on the basis of the analysis of the surface pressure (π)-mean molecular area (A) isotherms, surface compression modulus (C(s)(-1))-π curves, and plots of A versus mole fraction of INS (X(INS)). Our results indicate that intermolecular interactions between INS and PC depend on both the monolayer state and the structural characteristics of INS at the interface, which are strongly influenced by the subphase pH and salt content. Brewster angle microscopy (BAM) was applied to investigate the peptide aggregation pattern at the air-water interface in the presence of the studied lipid under any experimental condition investigated. The influence of the lipid on the INS behavior at the interface strongly depends on the subphase conditions.

Individual laboratory-measured discount rates predict field behavior

PubMed Central

Chabris, Christopher F.; Laibson, David; Morris, Carrie L.; Schuldt, Jonathon P.; Taubinsky, Dmitry

2009-01-01

We estimate discount rates of 555 subjects using a laboratory task and find that these individual discount rates predict inter-individual variation in field behaviors (e.g., exercise, BMI, smoking). The correlation between the discount rate and each field behavior is small: none exceeds 0.28 and many are near 0. However, the discount rate has at least as much predictive power as any variable in our dataset (e.g., sex, age, education). The correlation between the discount rate and field behavior rises when field behaviors are aggregated: these correlations range from 0.09-0.38. We present a model that explains why specific intertemporal choice behaviors are only weakly correlated with discount rates, even though discount rates robustly predict aggregates of intertemporal decisions. PMID:19412359

Individual laboratory-measured discount rates predict field behavior.

PubMed

Chabris, Christopher F; Laibson, David; Morris, Carrie L; Schuldt, Jonathon P; Taubinsky, Dmitry

2008-12-01

We estimate discount rates of 555 subjects using a laboratory task and find that these individual discount rates predict inter-individual variation in field behaviors (e.g., exercise, BMI, smoking). The correlation between the discount rate and each field behavior is small: none exceeds 0.28 and many are near 0. However, the discount rate has at least as much predictive power as any variable in our dataset (e.g., sex, age, education). The correlation between the discount rate and field behavior rises when field behaviors are aggregated: these correlations range from 0.09-0.38. We present a model that explains why specific intertemporal choice behaviors are only weakly correlated with discount rates, even though discount rates robustly predict aggregates of intertemporal decisions.

On the molecular basis of the receptor mosaic hypothesis of the engram.

PubMed

Agnati, Luigi F; Ferré, Sergi; Leo, Giuseppina; Lluis, Carme; Canela, Enric I; Franco, Rafael; Fuxe, Kjell

2004-08-01

1. This paper revisits the so-called "receptor mosaic hypothesis" for memory trace formation in the light of recent findings in "functional (or interaction) proteomics." The receptor mosaic hypothesis maintains that receptors may form molecular aggregates at the plasma membrane level representing part of the computational molecular networks. 2. Specific interactions between receptors occur as a consequence of the pattern of transmitter release from the source neurons, which release the chemical code impinging on the receptor mosaics of the target neuron. Thus, the decoding of the chemical message depends on the receptors forming the receptor mosaics and on the type of interactions among receptors and other proteins in the molecular network with novel long-term mosaics formed by their stabilization via adapter proteins formed in target neurons through the incoming neurotransmitter code. The internalized receptor heteromeric complexes or parts of them may act as transcription factors for the formation of such adapter proteins. 3. Receptor mosaics are formed both at the pre- and postsynaptic level of the plasma membranes and this phenomenon can play a role in the Hebbian behavior of some synaptic contacts. The appropriate "matching" of the pre- with the postsynaptic receptor mosaic can be thought of as the "clamping of the synapse to the external teaching signal." According to our hypothesis the behavior of the molecular networks at plasma membrane level to which the receptor mosaics belong can be set in a "frozen" conformation (i.e. in a frozen functional state) and this may represent a mechanism to maintain constant the input to a neuron. 4. Thus, we are suggesting that molecular networks at plasma membrane level may display multiple "attractors" each of which stores the memory of a specific neurotransmitter code due to a unique firing pattern. Hence, this mechanism may play a role in learning processes where the input to a neuron is likely to remain constant for a while.

Cluster growth mechanisms in Lennard-Jones fluids: A comparison between molecular dynamics and Brownian dynamics simulations

NASA Astrophysics Data System (ADS)

Jung, Jiyun; Lee, Jumin; Kim, Jun Soo

2015-03-01

We present a simulation study on the mechanisms of a phase separation in dilute fluids of Lennard-Jones (LJ) particles as a model of self-interacting molecules. Molecular dynamics (MD) and Brownian dynamics (BD) simulations of the LJ fluids are employed to model the condensation of a liquid droplet in the vapor phase and the mesoscopic aggregation in the solution phase, respectively. With emphasis on the cluster growth at late times well beyond the nucleation stage, we find that the growth mechanisms can be qualitatively different: cluster diffusion and coalescence in the MD simulations and Ostwald ripening in the BD simulations. We also show that the rates of the cluster growth have distinct scaling behaviors during cluster growth. This work suggests that in the solution phase the random Brownian nature of the solute dynamics may lead to the Ostwald ripening that is qualitatively different from the cluster coalescence in the vapor phase.

The Importance of End Groups for Solution-Processed Small-Molecule Bulk-Heterojunction Photovoltaic Cells.

PubMed

Duan, Ruomeng; Cui, Yong; Zhao, Yanfei; Li, Chen; Chen, Long; Hou, Jianhui; Wagner, Manfred; Baumgarten, Martin; He, Chang; Müllen, Klaus

2016-05-10

End groups in small-molecule photovoltaic materials are important owing to their strong influence on molecular stability, solubility, energy levels, and aggregation behaviors. In this work, a series of donor-acceptor pentads (D2 -A-D1 -A-D2 ) were designed and synthesized, aiming to investigate the effect of the end groups on the materials properties and photovoltaic device performance. These molecules share identical central A-D1 -A triads (with benzodithiophene as D1 and 6-carbonyl-thieno[3,4-b]thiophene as A), but with various D2 end groups composed of alkyl-substituted thiophene (T), thieno[3,2-b]thiophene (TT), and 2,2'-bithiophene (BT). The results indicate a relationship between conjugated segment/alkyl chain length of the end groups and the photovoltaic performance, which contributes to the evolving molecular design principles for high efficiency organic solar cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visualization of polymer relaxation in viscoelastic turbulent micro-channel flow.

PubMed

Tai, Jiayan; Lim, Chun Ping; Lam, Yee Cheong

2015-11-13

In micro-channels, the flow of viscous liquids e.g. water, is laminar due to the low Reynolds number in miniaturized dimensions. An aqueous solution becomes viscoelastic with a minute amount of polymer additives; its flow behavior can become drastically different and turbulent. However, the molecules are typically invisible. Here we have developed a novel visualization technique to examine the extension and relaxation of polymer molecules at high flow velocities in a viscoelastic turbulent flow. Using high speed videography to observe the fluorescein labeled molecules, we show that viscoelastic turbulence is caused by the sporadic, non-uniform release of energy by the polymer molecules. This developed technique allows the examination of a viscoelastic liquid at the molecular level, and demonstrates the inhomogeneity of viscoelastic liquids as a result of molecular aggregation. It paves the way for a deeper understanding of viscoelastic turbulence, and could provide some insights on the high Weissenberg number problem. In addition, the technique may serve as a useful tool for the investigations of polymer drag reduction.

Visualization of polymer relaxation in viscoelastic turbulent micro-channel flow

NASA Astrophysics Data System (ADS)

Tai, Jiayan; Lim, Chun Ping; Lam, Yee Cheong

2015-11-01

In micro-channels, the flow of viscous liquids e.g. water, is laminar due to the low Reynolds number in miniaturized dimensions. An aqueous solution becomes viscoelastic with a minute amount of polymer additives; its flow behavior can become drastically different and turbulent. However, the molecules are typically invisible. Here we have developed a novel visualization technique to examine the extension and relaxation of polymer molecules at high flow velocities in a viscoelastic turbulent flow. Using high speed videography to observe the fluorescein labeled molecules, we show that viscoelastic turbulence is caused by the sporadic, non-uniform release of energy by the polymer molecules. This developed technique allows the examination of a viscoelastic liquid at the molecular level, and demonstrates the inhomogeneity of viscoelastic liquids as a result of molecular aggregation. It paves the way for a deeper understanding of viscoelastic turbulence, and could provide some insights on the high Weissenberg number problem. In addition, the technique may serve as a useful tool for the investigations of polymer drag reduction.

The diffusion and conduction of lithium in poly(ethylene oxide)-based sulfonate ionomers

NASA Astrophysics Data System (ADS)

LaFemina, Nikki H.; Chen, Quan; Colby, Ralph H.; Mueller, Karl T.

2016-09-01

Pulsed field gradient nuclear magnetic resonance spectroscopy and dielectric relaxation spectroscopy have been utilized to investigate lithium dynamics within poly(ethylene oxide) (PEO)-based lithium sulfonate ionomers of varying ion content. The ion content is set by the fraction of sulfonated phthalates and the molecular weight of the PEO spacer, both of which can be varied independently. The molecular level dynamics of the ionomers are dominated by either Vogel-Fulcher-Tammann or Arrhenius behavior depending on ion content, spacer length, temperature, and degree of ionic aggregation. In these ionomers the main determinants of the self-diffusion of lithium and the observed conductivities are the ion content and ionic states of the lithium ion, which are profoundly affected by the interactions of the lithium ions with the ether oxygens of the polymer. Since many lithium ions move by segmental polymer motion in the ion pair state, their diffusion is significantly larger than that estimated from conductivity using the Nernst-Einstein equation.

Visualization of polymer relaxation in viscoelastic turbulent micro-channel flow

PubMed Central

Tai, Jiayan; Lim, Chun Ping; Lam, Yee Cheong

2015-01-01

In micro-channels, the flow of viscous liquids e.g. water, is laminar due to the low Reynolds number in miniaturized dimensions. An aqueous solution becomes viscoelastic with a minute amount of polymer additives; its flow behavior can become drastically different and turbulent. However, the molecules are typically invisible. Here we have developed a novel visualization technique to examine the extension and relaxation of polymer molecules at high flow velocities in a viscoelastic turbulent flow. Using high speed videography to observe the fluorescein labeled molecules, we show that viscoelastic turbulence is caused by the sporadic, non-uniform release of energy by the polymer molecules. This developed technique allows the examination of a viscoelastic liquid at the molecular level, and demonstrates the inhomogeneity of viscoelastic liquids as a result of molecular aggregation. It paves the way for a deeper understanding of viscoelastic turbulence, and could provide some insights on the high Weissenberg number problem. In addition, the technique may serve as a useful tool for the investigations of polymer drag reduction. PMID:26563615

Heritability and molecular-genetic basis of the P3 event-related brain potential: A genome-wide association study

PubMed Central

MALONE, STEPHEN M.; VAIDYANATHAN, UMA; BASU, SAONLI; MILLER, MICHAEL B.; MCGUE, MATT; IACONO, WILLIAM G.

2014-01-01

P3 amplitude is a candidate endophenotype for disinhibitory psychopathology, psychosis, and other disorders. The present study is a comprehensive analysis of the behavioral- and molecular-genetic basis of P3 amplitude and a P3 genetic factor score in a large community sample (N = 4,211) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric models indicated that as much as 65% of the variance in each measure was due to additive genes. All SNPs in aggregate accounted for approximately 40% to 50% of the heritable variance. However, analyses of individual SNPs did not yield any significant associations. Analyses of individual genes did not confirm previous associations between P3 amplitude and candidate genes but did yield a novel association with myelin expression factor 2 (MYEF2). Main effects of individual variants may be too small to be detected by GWAS without larger samples. PMID:25387705

Effect of pH on the adsorption of dodecylamine on montmorillonite: Insights from experiments and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Peng, Chenliang; Min, Fanfei; Liu, Lingyun

2017-12-01

The hydrophobic aggregation in cationic surfactant suspension is an effective method to enhance the dewatering of clay-rich tailing. The solution pH can affect the adsorption behavior of cationic surfactant on clay mineral. The effect of pH on the adsorption of dodecylamine (DDA) on montmorillonite was investigated by the sedimentation test and the characterization of flocs images, contact angle, adsorption quantity, and fourier transform infrared (FTIR) spectroscopy, as well as molecular dynamics (MD) simulation. It was found that DDA ions were adsorbed on montmorillonite basal surfaces mainly by physical adsorption, including the electrostatic attraction and hydrogen bonding. A certain number of neutral DDA molecules can favor the adsorption of DDA. At pH around 8, the effect of hydrophobic modification was the best because DDA molecules and ions form compact and well-organized monolayer. The MD simulation results were in good agreement with that of contact angle, adsorption quantity and FTIR.

The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

NASA Astrophysics Data System (ADS)

Siposova, Katarina; Pospiskova, Kristyna; Bednarikova, Zuzana; Safarik, Ivo; Safarikova, Mirka; Kubovcikova, Martina; Kopcansky, Peter; Gazova, Zuzana

2017-04-01

Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe3O4-based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15-20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15-20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran).

Biomarkers for ragwort poisoning in horses: identification of protein targets

PubMed Central

Moore, Rowan E; Knottenbelt, Derek; Matthews, Jacqueline B; Beynon, Robert J; Whitfield, Phillip D

2008-01-01

Background Ingestion of the poisonous weed ragwort (Senecio jacobea) by horses leads to irreversible liver damage. The principal toxins of ragwort are the pyrrolizidine alkaloids that are rapidly metabolised to highly reactive and cytotoxic pyrroles, which can escape into the circulation and bind to proteins. In this study a non-invasive in vitro model system has been developed to investigate whether pyrrole toxins induce specific modifications of equine blood proteins that are detectable by proteomic methods. Results One dimensional gel electrophoresis revealed a significant alteration in the equine plasma protein profile following pyrrole exposure and the formation of a high molecular weight protein aggregate. Using mass spectrometry and confirmation by western blotting the major components of this aggregate were identified as fibrinogen, serum albumin and transferrin. Conclusion These findings demonstrate that pyrrolic metabolites can modify equine plasma proteins. The high molecular weight aggregate may result from extensive inter- and intra-molecular cross-linking of fibrinogen with the pyrrole. This model has the potential to form the basis of a novel proteomic strategy aimed at identifying surrogate protein biomarkers of ragwort exposure in horses and other livestock. PMID:18691403

Non-linear optical response by functionalized gold nanospheres: identifying design principles to maximize the molecular photo-release.

PubMed

Bergamini, Luca; Voliani, Valerio; Cappello, Valentina; Nifosì, Riccardo; Corni, Stefano

2015-08-28

In a recent study by Voliani et al. [Small, 2011, 7, 3271], the electromagnetic field enhancement in the vicinity of the gold nanoparticle surface has been exploited to achieve photocontrolled release of a molecular cargo conjugated to the nanoparticles via 1,2,3-triazole, a photocleavable moiety. The aim of the present study is to investigate the mechanism of the photorelease by characterizing the nanoparticle aggregation status within the cells and simulating the electric field enhancement in a range of experimentally realistic geometries, such as single Au nanoparticles, dimers, trimers and random aggregates. Two plasmon-enhanced processes are examined for triazole photocleavage, i.e. three-photon excitation and third-harmonic-generation (one-photon) excitation. Taking into account the absorption cross sections of the triazole, we conclude that the latter mechanism is more efficient, and provides a photocleavage rate that explains the experimental findings. Moreover, we determine which aggregate geometries are required to maximize the field enhancement, and the dependence of such enhancement on the excitation wavelength. Our results provide design principles for maximizing the multiphoton molecular photorelease by such functionalized gold nanoparticles.

A comparison of biophysical characterization techniques in predicting monoclonal antibody stability.

PubMed

Thiagarajan, Geetha; Semple, Andrew; James, Jose K; Cheung, Jason K; Shameem, Mohammed

2016-01-01

With the rapid growth of biopharmaceutical product development, knowledge of therapeutic protein stability has become increasingly important. We evaluated assays that measure solution-mediated interactions and key molecular characteristics of 9 formulated monoclonal antibody (mAb) therapeutics, to predict their stability behavior. Colloidal interactions, self-association propensity and conformational stability were measured using effective surface charge via zeta potential, diffusion interaction parameter (kD) and differential scanning calorimetry (DSC), respectively. The molecular features of all 9 mAbs were compared to their stability at accelerated (25°C and 40°C) and long-term storage conditions (2-8°C) as measured by size exclusion chromatography. At accelerated storage conditions, the majority of the mAbs in this study degraded via fragmentation rather than aggregation. Our results show that colloidal stability, self-association propensity and conformational characteristics (exposed tryptophan) provide reasonable prediction of accelerated stability, with limited predictive value at 2-8°C stability. While no correlations to stability behavior were observed with onset-of-melting temperatures or domain unfolding temperatures, by DSC, melting of the Fab domain with the CH2 domain suggests lower stability at stressed conditions. The relevance of identifying appropriate biophysical assays based on the primary degradation pathways is discussed.

Emergence of Life-Like Properties from Dissipative Self-Assembly of Nanoparticles

NASA Astrophysics Data System (ADS)

Ilday, Serim; Makey, Ghaith; Akguc, Gursoy B.; Yavuz, Ozgun; Tokel, Onur; Pavlov, Ihor; Gulseren, Oguz; Ilday, F. Omer

A profoundly fundamental question at the interface between physics and biology remains open: What are the minimum requirements for emergence of life-like properties from non-living systems? Here, we address this question and report emergent complex behavior of tens to thousands of colloidal nanoparticles in a system designed to be as plain as possible: The system is driven far from equilibrium by ultrafast laser pulses, which create spatiotemporal temperature gradients, inducing Marangoni-type flow that drags the particles towards aggregation; strong Brownian motion, used as source of fluctuations, opposes aggregation. Nonlinear feedback mechanisms naturally arise between the flow, the aggregate, and Brownian motion, allowing fast external control with minimal intervention. Consequently, complex behavior, analogous to those commonly seen in living organisms, emerges, whereby the aggregates can self-sustain, self-regulate, self-replicate, self-heal and can be transferred from one location to another, all within seconds. Aggregates can comprise of only one pattern or bifurcated patterns can co-exist, compete, survive or die.

Structure and aggregation in model tetramethylurea solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Rini; Patey, G. N., E-mail: patey@chem.ubc.ca

The structure of model aqueous tetramethylurea (TMU) solutions is investigated employing large-scale (32 000, 64 000 particles) molecular dynamics simulations. Results are reported for TMU mole fractions, X{sub t}, ranging from infinite dilution up to 0.07, and for two temperatures, 300 and 330 K. Two existing force fields for TMU-water solutions are considered. These are the GROMOS 53A6 united-atom TMU model combined with SPC/E water [TMU(GROMOS-UA)/W(SPC/E)], and the more frequently employed AMBER03 all-atom force field for TMU combined with the TIP3P water model [TMU(AMBER-AA)/W(TIP3P)]. It is shown that TMU has a tendency towards aggregation for both models considered, but the tendency ismore » significantly stronger for the [TMU(AMBER-AA)/W(TIP3P)] force field. For this model signs of aggregation are detected at X{sub t} = 0.005, aggregation is a well established feature of the solution at X{sub t} = 0.02, and the aggregates increase further in size with increasing concentration. This is in agreement with at least some experimental studies, which report signals of aggregation in the low concentration regime. The TMU aggregates exhibit little structure and are simply loosely ordered, TMU-rich regions of solution. The [TMU(GROMOS-UA)/W(SPC/E)] model shows strong signs of aggregation only at higher concentrations (X{sub t} ≳ 0.04), and the aggregates appear more loosely ordered, and less well-defined than those occurring in the [TMU(AMBER-AA)/W(TIP3P)] system. For both models, TMU aggregation increases when the temperature is increased from 300 to 330 K, consistent with an underlying entropy driven, hydrophobic interaction mechanism. At X{sub t} = 0.07, the extra-molecular correlation length expected for microheterogeneous solutions has become comparable with the size of the simulation cell for both models considered, indicating that even the systems simulated here are sufficiently large only at low concentrations.« less

Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells.

PubMed

Zarà, Marta; Canobbio, Ilaria; Visconte, Caterina; Canino, Jessica; Torti, Mauro; Guidetti, Gianni Francesco

2018-08-01

Tumor cell-induced platelet aggregation represents a critical process both for successful metastatic spread of the tumor and for the development of thrombotic complications in cancer patients. To get further insights into this process, we investigated and compared the molecular mechanisms of platelet aggregation induced by two different breast cancer cell lines (MDA-MB-231 and MCF7) and a colorectal cancer cell line (Caco-2). All the three types of cancer cells were able to induce comparable platelet aggregation, which, however, was observed exclusively in the presence of CaCl 2 and autologous plasma. Aggregation was supported both by fibrinogen binding to integrin αIIbβ3 as well as by fibrin formation, and was completely prevented by the serine protease inhibitor PPACK. Platelet aggregation was preceded by generation of low amounts of thrombin, possibly through tumor cells-expressed tissue factor, and was supported by platelet activation, as revealed by stimulation of phospholipase C, intracellular Ca 2+ increase and activation of Rap1b GTPase. Pharmacological inhibition of phospholipase C, but not of phosphatidylinositol 3-kinase or Src family kinases prevented tumor cell-induced platelet aggregation. Tumor cells also induced dense granule secretion, and the stimulation of the P2Y12 receptor by released ADP was found to be necessary for complete platelet aggregation. By contrast, prevention of thromboxane A 2 synthesis by aspirin did not alter the ability of all the cancer cell lines analyzed to induce platelet aggregation. These results indicate that tumor cell-induced platelet aggregation is not related to the type of the cancer cells or to their metastatic potential, and is triggered by platelet activation and secretion driven by the generation of small amount of thrombin from plasma and supported by the positive feedback signaling through secreted ADP. Copyright © 2018 Elsevier Inc. All rights reserved.

Asp-Gly based peptides confined at the surface of cationic gemini surfactant aggregates.

PubMed

Brizard, Aurélie; Dolain, Christel; Huc, Ivan; Oda, Reiko

2006-04-11

Cationic gemini surfactants complexed with anionic oligoglycine-aspartate (called gemini peptides hereafter) were synthesized, and their aggregation behaviors were studied. The effects of the hydrophobic chain length (C10-C22) and the length of the oligoglycine (0-4) were investigated, and it was clearly shown by critical micellar concentration, Krafft temperature, and isothermal surface pressure measurements that the hydrophobic effect and interpeptidic interaction influence the aggregation behavior in a cooperative manner. Below their Krafft temperatures, some of them formed both hydro- and organogels with three-dimensional networks and the Fourier transform infrared measurements show the presence of interpeptidic hydrogen bonds.

J-aggregation of a water-soluble tetracationic porphyrin in mixed LB films with a calix[8]arene carboxylic acid derivative.

PubMed

Miguel, Gustavo de; Pérez-Morales, Marta; Martín-Romero, María T; Muñoz, Eulogia; Richardson, Tim H; Camacho, Luis

2007-03-27

The molecular organization of a mixed film, containing a water-soluble tetracationic porphyrin (TMPyP) and a p-tert-butyl calix[8]arene octacarboxylic acid derivative (C8A), at the air-water interface and on a solid support (LB film), has been investigated. Although the TMPyP aggregation was not detected at the air-water interface, TMPyP J-aggregates have been found in the LB films (Y-type). Unlike tetraanionic porphyrins, for example TSPP, the TMPyP J-aggregates are not induced by a zwitterion formation. The TMPyP J-aggregation is a result of a "double comb" configuration, where porphyrins from opposite layers are interwoven in a linear infinite J-aggregate. Our results confirm that TMPyP molecules tend to self-aggregate strongly, provided the electrostatic repulsions of their peripheral groups are cancelled by the anionic groups of the C8A matrix.

The cell aggregating propensity of probiotic actinobacterial isolates: isolation and characterization of the aggregation inducing peptide pheromone.

PubMed

Muthu Selvam, Ramu; Vinothini, Gopal; Palliyarai Thaiyammal, Sethuramalingam; Latha, Selvanathan; Chinnathambi, Arunachalam; Dhanasekaran, Dharumadurai; Padmanabhan, Parasuraman; Ali Alharbi, Sulaiman; Archunan, Govindaraju

2016-01-01

The auto-aggregating ability of a probiotic is a prerequisite for colonization and protection of the gastrointestinal tract, whereas co-aggregation provides a close interaction with pathogenic bacteria. Peptide pheromone mediated signaling has been studied in several systems. However, it has not yet been explored in prokaryotes, especially actinobacteria. Hence, in the present study, the diffusible aggregation promoting factor was purified from the culture supernatant of a potent actinobacterial probiont and characterized using 20 different actinobacterial cultures isolated from the gut region of chicken and goat. The results showed that the pheromone-like compound induces the aggregation propensity of treated isolates. The factor was found to be a heat stable, acidic pH resistant, low molecular weight peptide which enhances the biofilm forming ability of other actinobacterial isolates. The aggregation promoting factor represents a bacterial sex factor (pheromone) and its characterization confirms its usage in the probiotic formulation.

Multiscale simulation of red blood cell aggregation

NASA Astrophysics Data System (ADS)

Bagchi, P.; Popel, A. S.

2004-11-01

In humans and other mammals, aggregation of red blood cells (RBC) is a major determinant to blood viscosity in microcirculation under physiological and pathological conditions. Elevated levels of aggregation are often related to cardiovascular diseases, bacterial infection, diabetes, and obesity. Aggregation is a multiscale phenomenon that is governed by the molecular bond formation between adjacent cells, morphological and rheological properties of the cells, and the motion of the extra-cellular fluid in which the cells circulate. We have developed a simulation technique using front tracking methods for multiple fluids that includes the multiscale characteristics of aggregation. We will report the first-ever direct computer simulation of aggregation of deformable cells in shear flows. We will present results on the effect of shear rate, strength of the cross-bridging bonds, and the cell rheological properties on the rolling motion, deformation and subsequent breakage of an aggregate.

Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

PubMed Central

Tanase, Maya; Urbanska, Aleksandra M.; Zolla, Valerio; Clement, Cristina C.; Huang, Liling; Morozova, Kateryna; Follo, Carlo; Goldberg, Michael; Roda, Barbara; Reschiglian, Pierluigi; Santambrogio, Laura

2016-01-01

Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis. PMID:26776680

Molecular dynamics simulations of structural transformation of perfluorooctane sulfonate (PFOS) at water/rutile interfaces.

PubMed

He, Guangzhi; Zhang, Meiyi; Zhou, Qin; Pan, Gang

2015-09-01

Concentration and salinity conditions are the dominant environmental factors affecting the behavior of perfluorinated compounds (PFCs) on the surfaces of a variety of solid matrices (suspended particles, sediments, and natural minerals). However, the mechanism has not yet been examined at molecular scales. Here, the structural transformation of perfluorooctane sulfonate (PFOS) at water/rutile interfaces induced by changes of the concentration level of PFOS and salt condition was investigated using molecular dynamics (MD) simulations. At low and intermediate concentrations all PFOS molecules directly interacted with the rutile (110) surface mainly by the sulfonate headgroups through electrostatic attraction, yielding a typical monolayer structure. As the concentration of PFOS increased, the molecules aggregated in a complex multi-layered structure, where an irregular assembling configuration was adsorbed on the monolayer structure by the van der Waals interactions between the perfluoroalkyl chains. When adding CaCl2 to the system, the multi-layered structure changed to a monolayer again, indicating that the addition of CaCl2 enhanced the critical concentration value to yield PFOS multilayer assemblies. The divalent Ca(2+) substituted for monovalent K(+) as the bridging counterion in PFOS adsorption. MD simulation may trigger wide applications in study of perfluorinated compounds (PFCs) from atomic/molecular scale. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contrasting self-aggregation over land and ocean surfaces

NASA Astrophysics Data System (ADS)

Inda Diaz, H. A.; O'Brien, T. A.

2017-12-01

The spontaneous organization of convection into clusters, or self-aggregation, demonstrably changes the nature and statistics of precipitation. While there has been much recent progress in this area, the processes that control self-aggregation are still poorly understood. Most of the work to date has focused on self-aggregation over ocean-like surfaces, but it is particularly pressing to understand what controls convective aggregation over land, since the associated change in precipitation statistics—between non-aggregated and aggregated convection—could have huge impacts on society and infrastructure. Radiative-convective equilibrium (RCE), has been extensively used as an idealized framework to study the tropical atmosphere. Self-aggregation manifests in numerous numerical models of RCE, nevertheless, there is still a lack of understanding in how it relates to convective organization in the observed world. Numerous studies have examined self-aggregation using idealized Cloud Resolving Models (CRMs) and General Circulation Models over the ocean, however very little work has been done on RCE and self-aggregation over land. Idealized models of RCE over ocean have shown that aggregation is sensitive to sea surface temperature (SST), more intense precipitation occurs in aggregated systems, and a variety of feedbacks—such as surface flux, cloud radiative, and upgradient moisture transport— contribute to the maintenance of aggregation, however it is not clear if these results apply over land. Progress in this area could help relate understanding of self-aggregation in idealized simulations to observations. In order to explore the behavior of self-aggregation over land, we use a CRM to simulate idealized RCE over land. In particular, we examine the aggregation of convection and how it compares with aggregation over ocean. Based on previous studies, where a variety of different CRMs exhibit a SST threshold below which self-aggregation does not occur, we hypothesize that idealized land simulations will exhibit similar threshold behavior when there is an adequate surface moisture supply. We systematically explore this by varying parameters that exert strong control on the surface enthalpy and moisture budget, such as type of land, surface albedo, and greenhouse gas concentration.

Molecular self-assembly in substituted alanine derivatives: XRD, Hirshfeld surfaces and DFT studies

NASA Astrophysics Data System (ADS)

Rajalakshmi, Periasamy; Srinivasan, Navaneethakrishnan; Sivaraman, Gandhi; Razak, Ibrahim Abdul; Rosli, Mohd Mustaqim; Krishnakumar, Rajaputi Venkatraman

2014-06-01

The molecular assemblage in the crystal structures of three modified chiral amino acids, two of which are isomeric D- and L-pairs boc-L-benzothienylalanine (BLA), boc-D-benzothienylalanine (BDA) and the other boc-D-naphthylalanine (NDA) differing from this pair very slightly in the chemical modification introduced, is accurately described. The aggregation of amino acid molecules is similar in all the crystals and may be described as a twisted double helical ladder in which two complementary long helical chains formed through O-H⋯O hydrogen bonds are interconnected through the characteristic head-to-tail N-H⋯O hydrogen bonds. Thus the molecular aggregation enabled through classical hydrogen bonds may be regarded as a mimic of the characteristic double helical structure of DNA. Also, precise structural information involving these amino acid molecules with lower symmetry exhibiting higher trigonal symmetry in their self-assembly is expected to throw light on the nature and strength of intermolecular interactions and their role in self-assembly of molecular aggregates, which are crucial in developing new or at least supplement existing crystal engineering strategies. Single crystal X-ray analysis and their electronic structures were calculated at the DFT level with a detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions in building different supramolecular architectures.

Understanding curcumin-induced modulation of protein aggregation.

PubMed

Ahmad, Basir; Borana, Mohanish S; Chaudhary, Ankur P

2017-07-01

Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils. Copyright © 2016 Elsevier B.V. All rights reserved.

Soil Organic Matter (SOM): Molecular Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, Amity

Molecular simulation is a powerful tool used to gain an atomistic, molecular, and nanoscale level understanding of the structure, dynamics, and interactions from adsorption on minerals and assembly in aggregates of soil organic matter (SOM). Given the importance of SOM fate and persistence in soils and the current knowledge gaps, applications of atomistic scale simulations to study the complex compounds in SOM and their interactions in self-assembled aggregates composed of different organic matter compounds and with mineral surfaces of different types common in soils are few and far between. Here, we describe various molecular simulation methods that are currently inmore » use in various areas and applicable to SOM research, followed by a brief survey of specific applications to SOM research and an illustration with our own recent efforts in this area. We conclude with an outlook and the challenges for future research in this area.« less

Factors that affect molecular weight distribution of Suwannee river fulvic acid as determined by electrospray ionization/mass spectrometry

USGS Publications Warehouse

Rostad, Colleen E.; Leenheer, Jerry A.

2004-01-01

Effects of methylation, molar response, multiple charging, solvents, and positive and negative ionization on molecular weight distributions of aquatic fulvic acid were investigated by electrospray ionization/mass spectrometry. After preliminary analysis by positive and negative modes, samples and mixtures of standards were derivatized by methylation to minimize ionization sites and reanalyzed.Positive ionization was less effective and produced more complex spectra than negative ionization. Ionization in methanol/water produced greater response than in acetonitrile/water. Molar response varied widely for the selected free acid standards when analyzed individually and in a mixture, but after methylation this range decreased. After methylation, the number average molecular weight of the Suwannee River fulvic acid remained the same while the weight average molecular weight decreased. These differences are probably indicative of disaggregation of large aggregated ions during methylation. Since the weight average molecular weight decreased, it is likely that aggregate formation in the fulvic acid was present prior to derivatization, rather than multiple charging in the mass spectra.

Non-aggregated axially disubstituted silicon phthalocyanines bearing electropolymerizable ligands and their aggregation, electropolymerizaton and thermal properties.

PubMed

Biyiklioglu, Zekeriya; Bas, Huseyin; Alp, Hakan

2015-08-21

A novel series of axially disubstituted silicon(iv) phthalocyanines bearing electropolymerizable ligands were designed and synthesized for the first time. The silicon(iv) phthalocyanines were characterized by various spectroscopic techniques as well as elemental analysis. The aggregation behavior of the SiPcs were examined in different solvents and at different concentrations in chloroform. In all the studied solvents and concentrations, the SiPcs were non-aggregated. The thermal behavior of the silicon(iv) phthalocyanines was also studied. The electropolymerization properties of the silicon(iv) phthalocyanines were investigated by cyclic and square wave voltammetry. This study is the first example of the electropolymerization of axially disubstituted silicon phthalocyanines. The type of axial ligand on the phthalocyanine ring did not show any effect on the absorption and thermal properties but influenced the electropolymerization of the phthalocyanines.

Aggregation behavior of fullerenes in aqueous solutions: a capillary electrophoresis and asymmetric flow field-flow fractionation study.

PubMed

Astefanei, Alina; Núñez, Oscar; Galceran, Maria Teresa; Kok, Wim Th; Schoenmakers, Peter J

2015-10-01

In this work, the electrophoretic behavior of hydrophobic fullerenes [buckminsterfullerene (C60), C70, and N-methyl-fulleropyrrolidine (C60-pyrr)] and water-soluble fullerenes [fullerol (C60(OH)24); polyhydroxy small gap fullerene, hydrated (C120(OH)30); C60 pyrrolidine tris acid (C60-pyrr tris acid); and (1,2-methanofullerene C60)-61-carboxylic acid (C60CHCOOH)] in micellar electrokinetic capillary chromatography (MECC) was evaluated. The aggregation behavior of the water-soluble compounds in MECC at different buffer and sodium dodecyl sulfate (SDS) concentrations and pH values of the background electrolyte (BGE) was studied by monitoring the changes observed in the electrophoretic pattern of the peaks. Broad and distorted peaks that can be attributed to fullerene aggregation were obtained in MECC which became narrower and more symmetric by working at low buffer and SDS concentrations (below the critical micelle concentration, capillary zone electrophoresis (CZE) conditions). For the characterization of the suspected aggregates formed (size and shape), asymmetrical flow field-flow fractionation (AF4) and transmission electron microscopy (TEM) were used. The results showed that the increase in the buffer concentration promoted the aggregation of the particles, while the presence of SDS micelles revealed multiple peaks corresponding to particles of different aggregation degrees. Furthermore, MECC has been applied for the first time for the analysis of C60 in two different cosmetic products (i.e., anti-aging serum and facial mask).

Glyoxal administration induces formation of high molecular weight aggregates of hemoglobin exhibiting amyloidal nature in experimental rats: An in vivo study.

PubMed

Banerjee, Sauradipta; Chakraborti, Abhay Sankar

2016-12-01

Glyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs). In the present study, we have investigated the effect of glyoxal on experimental rat hemoglobin in vivo after external administration of the α-dicarbonyl compound in animals. Gel electrophoretic profile of hemolysate collected from glyoxal-treated rats (32mg/kg body wt. dose) after one week exhibited the presence of some high molecular weight protein bands that were found to be absent for control, untreated rats. Mass spectrometric and absorption studies indicated that the bands represented hemoglobin. Further studies revealed that the fraction exhibited the presence of intermolecular cross β-sheet structure. Thus glyoxal administration induces formation of high molecular weight aggregates of hemoglobin with amyloid characteristics in rats. Aggregated hemoglobin fraction was found to exhibit higher stability compared to glyoxal-untreated hemoglobin. As evident from mass spectrometric studies, glyoxal was found to modify Arg-30β and Arg-31α of rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to induce amyloid-like aggregation of hemoglobin in rats. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, the above findings may be physiologically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydrodynamic effects on β-amyloid (16-22) peptide aggregation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiricotto, Mara; Sterpone, Fabio, E-mail: fabio.sterpone@ibpc.fr; Melchionna, Simone

Computer simulations based on simplified representations are routinely used to explore the early steps of amyloid aggregation. However, when protein models with implicit solvent are employed, these simulations miss the effect of solvent induced correlations on the aggregation kinetics and lifetimes of metastable states. In this work, we apply the multi-scale Lattice Boltzmann Molecular Dynamics technique (LBMD) to investigate the initial aggregation phases of the amyloid Aβ{sub 16−22} peptide. LBMD includes naturally hydrodynamic interactions (HIs) via a kinetic on-lattice representation of the fluid kinetics. The peptides are represented by the flexible OPEP coarse-grained force field. First, we have tuned themore » essential parameters that control the coupling between the molecular and fluid evolutions in order to reproduce the experimental diffusivity of elementary species. The method is then deployed to investigate the effect of HIs on the aggregation of 100 and 1000 Aβ{sub 16−22} peptides. We show that HIs clearly impact the aggregation process and the fluctuations of the oligomer sizes by favouring the fusion and exchange dynamics of oligomers between aggregates. HIs also guide the growth of the leading largest cluster. For the 100 Aβ{sub 16−22} peptide system, the simulation of ∼300 ns allowed us to observe the transition from ellipsoidal assemblies to an elongated and slightly twisted aggregate involving almost the totality of the peptides. For the 1000 Aβ{sub 16−22} peptides, a system of unprecedented size at quasi-atomistic resolution, we were able to explore a branched disordered fibril-like structure that has never been described by other computer simulations, but has been observed experimentally.« less

Growth-incompetent monomers of human calcitonin lead to a noncanonical direct relationship between peptide concentration and aggregation lag time.

PubMed

Kamgar-Parsi, Kian; Hong, Liu; Naito, Akira; Brooks, Charles L; Ramamoorthy, Ayyalusamy

2017-09-08

The role of the peptide hormone calcitonin in skeletal protection has led to its use as a therapeutic for osteoporosis. However, calcitonin aggregation into amyloid fibrils limits its therapeutic efficacy, necessitating a modification of calcitonin's aggregation kinetics. Here, we report a direct relationship between human calcitonin (hCT) concentration and aggregation lag time. This kinetic trend was contrary to the conventional understanding of amyloid aggregation and persisted over a range of aggregation conditions, as confirmed by thioflavin-T kinetics assays, CD spectroscopy, and transmission EM. Dynamic light scattering, 1 H NMR experiments, and seeded thioflavin-T assay results indicated that differences in initial peptide species contribute to this trend more than variations in the primary nucleus formation rate. On the basis of kinetics modeling results, we propose a mechanism whereby a structural conversion of hCT monomers is needed before incorporation into the fibril. Our kinetic mechanism recapitulates the experimentally observed relationship between peptide concentration and lag time and represents a novel mechanism in amyloid aggregation. Interestingly, hCT at low pH and salmon calcitonin (sCT) exhibited the canonical inverse relationship between concentration and lag time. Comparative studies of hCT and sCT with molecular dynamics simulations and CD indicated an increased α-helical structure in sCT and low-pH hCT monomers compared with neutral-pH hCT, suggesting that α-helical monomers represent a growth-competent species, whereas unstructured random coil monomers represent a growth-incompetent species. Our finding that initial monomer concentration is positively correlated with lag time in hCT aggregation could help inform future efforts for improving therapeutic applications of CT. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Collective Behavior of Amoebae in Thin Films

NASA Astrophysics Data System (ADS)

Bae, Albert

2005-03-01

We have discovered new aspects of social behavior in Dictyostelium discoideum by culturing high density colonies in liquid media depleted of nutrients in confined geometries by using three different preparations: I. thin (15-40um thick) and II. ultrathin (<3um) films of liquid media with a mineral oil overlayer, and III. microfluidic chambers fabricated in PDMS (˜7um tall). We find greatly reduced, if not eliminated, cell on cell layering in the microfluidic system when compared to the wetting layer preparations. The ultrathin films reveal robust behavior of cells despite flattening that increased their areas by over an order of magnitude. We also observed that the earliest synchronized response of cells following the onset of starvation, a precursor to aggregation, was hastened by reducing the thickness of the aqueous culture layer. We were surprised to find that the threshold concentration for aggregation was raised by thin film confinement when compared to bulk behavior. Finally, both the ultra thin and microfluidic preparations reveal, with new clarity, vortex states of aggregation.

Deformation Behavior of Recycled Concrete Aggregate during Cyclic and Dynamic Loading Laboratory Tests

PubMed Central

Sas, Wojciech; Głuchowski, Andrzej; Gabryś, Katarzyna; Soból, Emil; Szymański, Alojzy

2016-01-01

Recycled concrete aggregate (RCA) is a relatively new construction material, whose applications can replace natural aggregates. To do so, extensive studies on its mechanical behavior and deformation characteristics are still necessary. RCA is currently used as a subbase material in the construction of roads, which are subject to high settlements due to traffic loading. The deformation characteristics of RCA must, therefore, be established to find the possible fatigue and damage behavior for this new material. In this article, a series of triaxial cyclic loading and resonant column tests is used to characterize fatigue in RCA as a function of applied deviator stress after long-term cyclic loading. A description of the shakedown phenomenon occurring in the RCA and calculations of its resilient modulus (Mr) as a function of fatigue are also presented. Test result analysis with the stress-life method on the Wohler S-N diagram shows the RCA behavior in accordance with the Basquin law. PMID:28773905

"Mixed-charge self-assembled monolayers" as a facile method to design pH-induced aggregation of large gold nanoparticles for near-infrared photothermal cancer therapy.

PubMed

Li, Huan; Liu, Xiangsheng; Huang, Nan; Ren, Kefeng; Jin, Qiao; Ji, Jian

2014-01-01

The acidic microenvironment of tumor tissues has proven to be one of the major differences from other normal tissues. The near-infrared (NIR) light irradiation of aggregated gold nanoparticles in a tumor acidic pH-induced manner could then provide an effect approach to treat solid tumors with the advantage of minimizing the undesired damage to normal tissues. Although it is well-known the aggregation of larger nanoparticles will result in a better NIR photothermal effect, the preparation of pH-sensitive gold nanoparticles in large sizes remains a big challenge because of their worse dispersive stability. In this paper, we introduce a facile way to endow large gold nanoparticles with tunable pH-aggregation behaviors by modifying the nanoparticle surface with mixed-charge self-assembly monolayers compromising positively and negatively charged thiol ligands. Four different size nanoparticles were used to study the general principle of tailoring the pH-induced aggregation behaviors of mixed-charge gold nanoparticles (MC-GNPs) by adjusting the surface ligand composition. With proper surface ligand composition, the MC-GNPs in four different sizes that all exhibited aggregation at tumor acidic pH were obtained. The biggest MC-GNPs showed the most encouraging aggregation-enhanced photothermal efficacy in vitro when they formed aggregates. The mixed-charge self-assembled monolayers were then proved as a facile method to design pH-induced aggregation of large gold nanoparticles for better NIR photothermal cancer therapy.

Two compounds in bed bug feces are sufficient to elicit off-host aggregation by bed bugs, Cimex lectularius.

PubMed

Olson, Joelle F; Vers, Leonard M Ver; Moon, Roger D; Kells, Stephen A

2017-01-01

After feeding, bed bugs aggregate in cracks and crevices near a host. Aggregation and arrestment are mediated by tactile and chemical stimuli associated with the bugs' feces and exuviae. Volatiles derived from fecally stained filter papers were analyzed by solid-phase microextraction (SPME) and evaluated using a multichoice behavioral assay to determine their impact on bed bug aggregation. In addition, crude fecal extracts were collected in methanol, analyzed by gas chromatography coupled with electroantennogram detection (GC-EAD) and mass spectrometry (GC-MS) and evaluated in open-air multichoice behavioral assays. The SPME method was used to detect (E)-2-hexenal and (E)-2-octenal in heated bed bug feces. The presence of these two volatile components did not affect aggregation. Analysis of the crude fecal extracts revealed several semi-volatile nitrogenous compounds, a carboxylic acid and a sulfur-based compound. Adult antennae responded to compounds eluted from three regions of the crude extract using GC-EAD. A combination of two compounds, dimethyl trisulfide and methyldiethanolamine, resulted in aggregation responses equivalent to the original crude extract. Bed bug aggregation is mediated by semi-volatile compounds derived from fecal extracts, and two compounds are sufficient to elicit aggregation. The two compounds identified here could be used to enhance the effectiveness of insecticidal applications or improve monitoring techniques. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Targeting the Blind Spot of Polycationic Nanocarrier-Based siRNA Delivery

PubMed Central

Zheng, Mengyao; Pavan, Giovanni M.; Neeb, Manuel; Schaper, Andreas K.; Danani, Andrea; Klebe, Gerhard; Merkel, Olivia M.; Kissel, Thomas

2013-01-01

Polycationic nanocarriers attract increasing attention to the field of siRNA delivery. We investigated the self-assembly of siRNA vs pDNA with polycations, which are broadly used for nonviral gene and siRNA delivery. Although polyethyleneimine (PEI) was routinely adopted as siRNA carrier based on its efficacy in delivering pDNA, it has not been investigated yet why PEI efficiently delivers pDNA to cells but is controversially discussed in terms of efficacy for siRNA delivery. We are the first to investigate the self-assembly of PEI/siRNA vs PEI/pDNA and the steps of complexation and aggregation through different levels of hierarchy on the atomic and molecular scale with the novel synergistic use of molecular modeling, molecular dynamics simulation, isothermal titration calorimetry, and other characterization techniques. We are also the fist to elucidate atomic interactions, size, shape, stoichiometry, and association dynamics for polyplexes containing siRNA vs pDNA. Our investigation highlights differences in the hierarchical mechanism of formation of related polycation–siRNA and polycation–pDNA complexes. The results of fluorescence quenching assays indicated a biphasic behavior of siRNA binding with polycations where molecular reorganization of the siRNA within the polycations occurred at lower N/P ratios (nitrogen/phosphorus). Our results, for the first time, emphasize a biphasic behavior in siRNA complexation and the importance of low N/P ratios, which allow for excellent siRNA delivery efficiency. Our investigation highlights the formulation of siRNA complexes from a thermodynamic point of view and opens new perspectives to advance the rational design of new siRNA delivery systems. PMID:23036046

Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

PubMed

Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

2016-10-01

This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

Aggregate Formation of Oligonucleotides that Assist Molecular Imaging for Tracking of the Oxygen Status in Tumor Tissue.

PubMed

Yoshihara, Kazuki; Takagi, Kohei; Son, Aoi; Kurihara, Ryohsuke; Tanabe, Kazuhito

2017-08-17

The use of DNA aggregates could be a promising strategy for the molecular imaging of biological functions. Herein, phosphorescent oligodeoxynucleotides were designed with the aim of visualizing oxygen fluctuation in tumor cells. DNA-ruthenium conjugates (DRCs) that consisted of oligodeoxynucleotides, a phosphorescent ruthenium complex, a pyrene unit for high oxygen responsiveness, and a nitroimidazole unit as a tumor-targeting unit were prepared. In general, oligonucleotides have low cell permeability because of their own negative charges; however, the DRC formed aggregates in aqueous solution due to the hydrophobic pyrene and nitroimidazole groups, and smoothly penetrated the cellular membrane to accumulate in tumor cells in a hypoxia-selective manner. The oxygen-dependent phosphorescence of DRC in cells was also observed. In vivo experiments revealed that aggregates of DRC accumulated in hypoxic tumor tissue that was transplanted into the left leg of mice, and showed that oxygen fluctuations in tumor tissue could be monitored by tracking of the phosphorescence emission of DRC. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanisms of oriented attachment of TiO2 nanocrystals in vacuum and humid environments: reactive molecular dynamics.

PubMed

Raju, Muralikrishna; van Duin, Adri C T; Fichthorn, Kristen A

2014-01-01

Oriented attachment (OA) of nanocrystals is now widely recognized as a key process in the solution-phase growth of hierarchical nanostructures. However, the microscopic origins of OA remain unclear. We perform molecular dynamics simulations using a recently developed ReaxFF reactive force field to study the aggregation of various titanium dioxide (anatase) nanocrystals in vacuum and humid environments. In vacuum, the nanocrystals merge along their direction of approach, resulting in a polycrystalline material. By contrast, in the presence of water vapor the nanocrystals reorient themselves and aggregate via the OA mechanism to form a single or twinned crystal. They accomplish this by creating a dynamic network of hydrogen bonds between surface hydroxyls and surface oxygens of aggregating nanocrystals. We determine that OA is dominant on surfaces that have the greatest propensity to dissociate water. Our results are consistent with experiment, are likely to be general for aqueous oxide systems, and demonstrate the critical role of solvent in nanocrystal aggregation. This work opens up new possibilities for directing nanocrystal growth to fabricate nanomaterials with desired shapes and sizes.

AIE Polymers: Synthesis, Properties, and Biological Applications.

PubMed

Zhan, Ruoyu; Pan, Yutong; Manghnani, Purnima Naresh; Liu, Bin

2017-05-01

Aggregation-caused quenching (ACQ) is a general phenomenon that is faced by traditional fluorescent polymers. Aggregation-induced emission (AIE) is exactly opposite to ACQ. AIE molecules are almost nonemissive in their molecularly dissolved state, but they can be induced to show high fluorescence in the aggregated or solid state. Incorporation of AIE phenomenon into polymer design has yielded various polymers with AIE characteristics. In this review, the recent progress of AIE polymers for biological applications is summarized. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside delays amyloid-β42 aggregation and reduces amyloid cytotoxicity.

PubMed

Dhouafli, Zohra; Leri, Manuela; Bucciantini, Monica; Stefani, Massimo; Gadhoumi, Hamza; Mahjoub, Borhane; Ben Jannet, Hichem; Guillard, Jérôme; Ksouri, Riadh; Saidani Tounsi, Moufida; Soto, Claudio; Hayouni, El Akrem

2018-03-26

Presently, misfolding and aggregation of amyloid-β 42 (Aβ 42 ) are considered early events in Alzheimer's disease (AD) pathogenesis. The use of natural products to inhibit the aggregation process and to protect cells from cytotoxicity of early aggregate grown at the onset of the aggregation path is one of the promising strategies against AD. Recently, we have purified a new powerful antioxidant and inhibitor of Aβ 42 aggregation from the leaves of Lawsonia inermis. The new compound was identified as a new Lawsoniaside; 1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside (THNG). Herein, we show that THNG interferes with Aβ 42 aggregation, inhibits its conformational change to a β-sheet-rich structure, decreases its polymerization into large fibrillar species, reduces oxidative stress, and aggregate cytotoxicity. These results indicate that THNG has great potential as a neuroprotective and therapeutic agent against AD. © 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Delocalized versus localized excitations in the photoisomerization of azobenzene-functionalized alkanethiolate SAMs

NASA Astrophysics Data System (ADS)

Bronsch, Wibke; Moldt, Thomas; Boie, Larissa; Gahl, Cornelius; Weinelt, Martin

2017-12-01

Self-assembled monolayers of azobenzene-functionalized alkanethiolates form molecular ensembles with preferential orientation and significant excitonic coupling among the azobenzene chromophores. We have studied their optical switching with differential reflectance and two-photon-photoemission spectroscopy tuning the excitation wavelength through the excitonically broadened S2 absorption band. While the effective isomerization cross-section increases towards shorter wavelengths, the fraction of cis molecules in the photostationary state decreases. We attribute this observation to the absorption of the cis isomer in the SAM. The photoisomerization in the SAM thereby follows the behavior of non-interacting chromophores in solution, despite the formation of H-aggregates. Our study thus reveals that photoswitching occurs via localized excitations while strongly excitonically coupled, delocalized states do not contribute significantly.

Multiplexed plasmonic sensing based on small-dimension nanohole arrays and intensity interrogation

PubMed Central

Yang, Jiun-Chan; Ji, Jin; Hogle, James M.; Larson, Dale N.

2009-01-01

We performed multiplexed sensing on nanohole array devices to simultaneously obtain information on molecular absorption, scattering, and refractive-index change, which were distinguished by using different array structures with distinct optical behavior. Up to 25 arrays were fabricated within a 65 μm × 50 μm area to provide real-time information of the local surface environment. The performance of multiplexed sensing was examined by flowing NaCl, coomassie blue, bovine serum albumin, and liposome solutions that exhibit different visible light absorption / scattering properties and different refractive indices. Experimental artifacts from light source fluctuation, sample injections, and light scattering induced by aggregates in solutions were detected by monitoring superwavelength holes or nanohole arrays with different periodicity and hole diameters. PMID:19157848

Association behaviors of dodecyltrimethylammonium bromide with double hydrophilic block co-polymer poly(ethylene glycol)-block-poly(glutamate sodium).

PubMed

Han, Yuchun; Xia, Lin; Zhu, Linyi; Zhang, Shusheng; Li, Zhibo; Wang, Yilin

2012-10-30

The association behaviors of single-chain surfactant dodecyltrimethylammonium bromide (DTAB) with double hydrophilic block co-polymers poly(ethylene glycol)-b-poly(sodium glutamate) (PEG(113)-PGlu(50) or PEG(113)-PGlu(100)) were investigated using isothermal titration microcalorimetry, cryogenic transmission electron microscopy, circular dichroism, ζ potential, and particle size measurements. The electrostatic interaction between DTAB and the oppositely charged carboxylate groups of PEG-PGlu induces the formation of super-amphiphiles, which further self-assemble into ordered aggregates. Dependent upon the charge ratios between DTAB and the glutamic acid residue of the co-polymer, the mixture solutions can change from transparent to opalescent without precipitation. Dependent upon the chain length of the PGlu block, the mixture of DTAB and PEG-PGlu diblocks can form two different aggregates at their corresponding electroneutral point. Spherical and rod-like aggregates are formed in the PEG(113)-PGlu(50)/DTAB mixture, while the vesicular aggregates are observed in the PEG(113)-PGlu(100)/DTAB mixture solution. Because the PEG(113)-PGlu(100)/DTAB super-amphiphile has more hydrophobic components than that of the PEG(113)-PGlu(50)/DTAB super-amphiphile, the former prefers forming the ordered aggregates with higher curvature, such as spherical and rod aggregates, but the latter prefers forming vesicular aggregates with lower curvature.

Generation of the displacement current by the transformation of J-aggregates in spreading monolayers of squarylium dye

NASA Astrophysics Data System (ADS)

Iwamoto, Mitsumasa; Majima, Yutaka; Hirayama, Fuminori; Furuki, Makoto; Pu, Lyong Sun

1992-07-01

Maxwell displacement currents generated from monolayers of squarylium dye with propyl groups (SQ) and from mixed monolayers with arachidic acid were investigated during the course of monolayer compression in connection with the formation of J-aggregates in the monolayers. Abrupt changes in the generation of displacement current were observed for monolayers of SQ due to the transformation between two types of J-aggregates with different absorption spectra. In contrast, for mixed monolayers with arachidic acid which show no transition of J-aggregates, abrupt changes in the displacement current were not observed. It was concluded that displacement current measurement is effective in the detection of the transformation of the molecular arrangement in aggregates.

Low molecular weight oligomers of amyloid peptides display β-barrel conformations: A replica exchange molecular dynamics study in explicit solvent

NASA Astrophysics Data System (ADS)

De Simone, Alfonso; Derreumaux, Philippe

2010-04-01

The self-assembly of proteins and peptides into amyloid fibrils is connected to over 40 pathological conditions including neurodegenerative diseases and systemic amyloidosis. Diffusible, low molecular weight protein and peptide oligomers that form in the early steps of aggregation appear to be the harmful cytotoxic species in the molecular etiology of these diseases. So far, the structural characterization of these oligomers has remained elusive owing to their transient and dynamic features. We here address, by means of full atomistic replica exchange molecular dynamics simulations, the energy landscape of heptamers of the amyloidogenic peptide NHVTLSQ from the beta-2 microglobulin protein. The simulations totaling 5 μs show that low molecular weight oligomers in explicit solvent consist of β-barrels in equilibrium with amorphous states and fibril-like assemblies. The results, also accounting for the influence of the pH on the conformational properties, provide a strong evidence of the formation of transient β-barrel assemblies in the early aggregation steps of amyloid-forming systems. Our findings are discussed in terms of oligomers cytotoxicity.

Hemoglobin bioconjugates with surface-protected gold nanoparticles in aqueous media: The stability depends on solution pH and protein properties.

PubMed

Del Caño, Rafael; Mateus, Lucia; Sánchez-Obrero, Guadalupe; Sevilla, José Manuel; Madueño, Rafael; Blázquez, Manuel; Pineda, Teresa

2017-11-01

The identification of the factors that dictate the formation and physicochemical properties of protein-nanomaterial bioconjugates are important to understand their behavior in biological systems. The present work deals with the formation and characterization of bioconjugates made of the protein hemoglobin (Hb) and gold nanoparticles (AuNP) capped with three different molecular layers (citrate anions (c), 6-mercaptopurine (MP) and ω-mercaptoundecanoic acid (MUA)). The main focus is on the behavior of the bioconjugates in aqueous buffered solutions in a wide pH range. The stability of the bioconjugates have been studied by UV-visible spectroscopy by following the changes in the localized surface resonance plasmon band (LSRP), Dynamic light scattering (DLS) and zeta-potential pH titrations. It has been found that they are stable in neutral and alkaline solutions and, at pH lower than the protein isoelectric point, aggregation takes place. Although the surface chemical properties of the AuNPs confer different properties in respect to colloidal stability, once the bioconjugates are formed their properties are dictated by the Hb protein corona. The protein secondary structure, as analyzed by Attenuated total reflectance infrared (ATR-IR) spectroscopy, seems to be maintained under the conditions of colloidal stability but some small changes in protein conformation take place when the bioconjugates aggregate. These findings highlight the importance to keep the protein structure upon interaction with nanomaterials to drive the stability of the bioconjugates. Copyright © 2017 Elsevier Inc. All rights reserved.

Insights into amyloid-like aggregation of H2 region of the C-terminal domain of nucleophosmin.

PubMed

Russo, Anna; Diaferia, Carlo; La Manna, Sara; Giannini, Cinzia; Sibillano, Teresa; Accardo, Antonella; Morelli, Giancarlo; Novellino, Ettore; Marasco, Daniela

2017-02-01

Nucleophosmin (NPM1) is a multifunctional protein involved in a variety of biological processes including the pathogenesis of several human malignancies and is the most frequently mutated gene in Acute Myeloid Leukemia (AML). To deepen the role of protein regions in its biological activities, lately we reported on the structural behavior of dissected C-terminal domain (CTD) helical fragments. Unexpectedly the H2 (residues 264-277) and H3 AML-mutated regions showed a remarkable tendency to form amyloid-like assemblies with fibrillar morphology and β-sheet structure that resulted as toxic when exposed to human neuroblastoma cells. More recently NPM1 was found to be highly expressed and toxic in neurons of mouse models of Huntington's disease (HD). Here we investigate the role of each residue in the β-strand aggregation process of H2 region of NPM1 by performing a systematic alanine scan of its sequence and structural and kinetic analyses of aggregation of derived peptides by means of Circular Dichorism (CD) and Thioflavin T (Th-T) assay. These solution state investigations pointed out the crucial role exerted by the basic amyloidogenic stretch of H2 (264-271) and to shed light on the initial and main interactions involved in fibril formation we performed studies on fibrils deriving from the related Ala peptides through the analysis of fibrils with birefringence of polarized optical microscopy and wide-angle X-ray scattering (WAXS). This analysis suggested that the presence of branched Ile 269 conferred preferential packing patterns that, instead, appeared geometrically hampered by the aromatic side-chain of Phe 268 . Present investigations could be useful to deepen the knowledge of AML molecular mechanisms and the role of cytoplasmatic aggregates of NPM1c+. Copyright © 2016 Elsevier B.V. All rights reserved.

Aggregate Size Dependence of Amyloid Adsorption onto Charged Interfaces

PubMed Central

2017-01-01

Amyloid aggregates are associated with a range of human neurodegenerative disorders, and it has been shown that neurotoxicity is dependent on aggregate size. Combining molecular simulation with analytical theory, a predictive model is proposed for the adsorption of amyloid aggregates onto oppositely charged surfaces, where the interaction is governed by an interplay between electrostatic attraction and entropic repulsion. Predictions are experimentally validated against quartz crystal microbalance–dissipation experiments of amyloid beta peptides and fragmented fibrils in the presence of a supported lipid bilayer. Assuming amyloids as rigid, elongated particles, we observe nonmonotonic trends for the extent of adsorption with respect to aggregate size and preferential adsorption of smaller aggregates over larger ones. Our findings describe a general phenomenon with implications for stiff polyions and rodlike particles that are electrostatically attracted to a surface. PMID:29284092

Ion Exchange and Solvent Extraction: Supramolecular Aspects of Solvent Exchange Volume 21

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gloe, Karsten; Tasker, Peter A; Oshima, Tatsuya

Preface The theme of supramolecular chemistry (SC), entailing the organization of multiple species through noncovalent interactions, has permeated virtually all aspects of chemical endeavor over the past several decades. Given that the observed behavior of discrete molecular species depends upon their weak interactions with one another and with matrix components, one would have to conclude that SC must indeed form part of the fabric of chemistry itself. A vast literature now serves to categorize SC phenomena within a body of consistent terminology. The word supramolecular itself appears in the titles of dozens of books, several journals, and a dedicated encyclopedia.more » Not surprisingly, the theme of SC also permeates the field of solvent extraction (SX), inspiring the framework for this volume of Ion Exchange and Solvent Extraction. It is attempted in the six chapters of this volume to identify both how supramolecular behavior occurs and is studied in the context of SX and how SC is influencing the current direction of SX. Researchers and practitioners have long dealt with supramolecular interactions in SX. Indeed, the use of polar extractant molecules in nonpolar media virtually assures that aggregative interactions will dominate the solution behavior of SX. Analytical chemists working in the 1930s to the 1950s with simple mono- and bidentate chelating ligands as extractants noted that extraction of metal ions obeyed complicated mass-action equilibria involving complex stoichiometries. As chemists and engineers developed processes for nuclear and hydrometallurgical applications in the 1950s and 1960s, the preference for aliphatic diluents only enhanced the complexity and supramolecular nature of extraction chemistry. Use of physical techniques such as light scattering and vapor-pressure measurements together with various spectroscopic methods revealed organic-phase aggregates from well-defined dimers to small aggregates containing a few extractant molecules to large inverse micelles swollen with water molecules. Extraction systems involving long-chain cations such as alkylammonium species or long-chain anions such as sulfonates or carboxylates proved especially prone to extensive aggregate formation. The related phenomenon of third-phase formation in SX systems, long misunderstood, is now yielding to spectroscopic and scattering techniques showing extensive long-range organization. Over the last 50 years, tools for studying the structure and thermodynamics of aggregation have grown increasingly sophisticated, leading to a rich and detailed understanding of what we can now recognize as SC phenomena in SX. In the 1970s and 1980s, the rapid growth of SC elicited a paradigm shift in SX. The influence of SC principles had two major effects on the course of SX research. First, it provided a framework for understanding the supramolecular behavior that was already well appreciated in the field of SX, though earlier without the SC terminology. Second, it provided the conceptual tools to control supramolecular behavior in SX, direct it for intended functionality, and to simplify it. Extraction by designed reagents has been steadily progressing ever since, with commercial applications emerging to successfully validate this approach. With the discovery of crown ethers in the late 1960s, the advancement of extractant design has fruitfully employed the concept of inclusion. While considerable initial progress occurred with such molecules, especially because of their affinity and selectivity for alkali and alkaline earth metals, other molecular platforms such as calixarenes have proven more versatile. Multidentate receptors for partial to full inclusion of cations, anions, ion pairs, as well as neutral species, have now become commonplace for selective extraction. This volume of Ion Exchange and Solvent Extraction examines how the principles of SC are being employed both in advancing the design of new highly selective SX systems and in understanding aggregation phenomena in SX systems. Chapter 1 discusses the nature and definition of SC and how it is used generally in design of novel SX reagents. Major approaches using SC principles are outlined and illustrated. Chapter 2 expands upon the theme of ion-pair recognition and introduces outer-sphere recognition of metal complexes, a novel idea with the potential for structural control of solvation, casting a new light on solvent modifiers. Chapter 3 reviews the large literature of calixarenes as extraction reagents for metal ions, where the synthetic versatility of this family of compounds has produced vast possibilities for inclusion and selective separations. Chapter 4 extends such chemistry to extraction of biomolecules, where the potential for selective separations is only beginning to be explored through site recognition in macromolecules. In Chapter 5, a detailed examination of the liquid-liquid interface as an expression of supramolecular phenomena i...« less

An improved size exclusion-HPLC method for molecular size distribution analysis of immunoglobulin G using sodium perchlorate in the eluent.

PubMed

Wang, Hsiaoling; Levi, Mark S; Del Grosso, Alfred V; McCormick, William M; Bhattacharyya, Lokesh

2017-05-10

Size exclusion (SE) high performance liquid chromatography (HPLC) is widely used for the molecular size distribution (MSD) analyses of various therapeutic proteins. We report development and validation of a SE-HPLC method for MSD analyses of immunoglobulin G (IgG) in products using a TSKgel SuperSW3000 column and eluting it with 0.4M NaClO 4 , a chaotropic salt, in 40mM phosphate buffer, pH 6.8. The chromatograms show distinct peaks of aggregates, tetramer, and two dimers, as well as the monomer and fragment peaks. In addition, the method offers about half the run time (12min), better peak resolution, improved peak shape and more stable base-line compared to HPLC methods reported in the literature, including that in the European Pharmacopeia (EP). A comparison of MSD analysis results between our method and the EP method shows interactions between the protein and the stationary phase and partial adsorption of aggregates and tetramer on the stationary phase, when the latter method is used. Thus, the EP method shows lower percent of aggregates and tetramer than are actually present in the products. In view of the fact that aggregates have been attributed to playing a critical role in adverse reactions due to IgG products, our observation raises a major concern regarding the actual aggregate content in these products since the EP method is widely used for MSD analyses of IgG products. Our method eliminates (or substantially reduces) the interactions between the proteins and stationary phase as well as the adsorption of proteins onto the column. Our results also show that NaClO 4 in the eluent is more effective in overcoming the protein/column interactions compared to Arg-HCl, another chaotropic salt. NaClO 4 is shown not to affect the molecular size and relative distribution of different molecular forms of IgG. The method validated as per ICH Q2(R1) guideline using IgG products, shows good specificity, accuracy, precision and a linear concentration dependence of peak areas for different molecular forms. In summary, our method gives more reliable results than the SE-HPLC methods for MSD analyses of IgG reported in the literature, including the EP, particularly for aggregates and tetramer. The results are interpreted in terms of ionic (polar) and hydrophobic interactions between the stationary phase and the IgG protein. Published by Elsevier B.V.

INTERNALIZATION AND FATE OF INDIVIDUAL MANUFACTURED NANOMATERIAL WITHIN LIVING CELLS

EPA Science Inventory

Using quantitative fluorescence imaging with single molecule sensitivity, combined with molecular biology techniques, we have been investigating the cellular interactions and fate of one nanoparticle or nanoscale aggregate at a time, identifying molecular interactions and cellula...

Aggregative group behavior in insect parasitic nematode dispersal.

PubMed

Shapiro-Ilan, David I; Lewis, Edwin E; Schliekelman, Paul

2014-01-01

Movement behavior of foraging animals is critical to the determination of their spatial ecology and success in exploiting resources. Individuals sometimes gain advantages by foraging in groups to increase their efficiency in garnering these resources. Group movement behavior has been studied in various vertebrates. In this study we explored the propensity for innate group movement behavior among insect parasitic nematodes. Given that entomopathogenic nematodes benefit from group attack and infection, we hypothesised that the populations would tend to move in aggregate in the absence of extrinsic cues. Movement patterns of entomopathogenic nematodes in sand were investigated when nematodes were applied to a specific locus or when the nematodes emerged naturally from infected insect hosts; six nematode species in two genera were tested (Heterorhabditis bacteriophora, Heterorhabditis indica, Steinernema carpocapsae, Steinernema feltiae, Steinernema glaseri and Steinernema riobrave). Nematodes were applied in aqueous suspension via filter paper discs or in infected insect host cadavers (to mimic emergence in nature). We discovered that nematode dispersal resulted in an aggregated pattern rather than a random or uniform distribution; the only exception was S. glaseri when emerging directly from infected hosts. The group movement may have been continuous from the point of origin, or it may have been triggered by a propensity to aggregate after a short period of random movement. To our knowledge, this is the first report of group movement behavior in parasitic nematodes in the absence of external stimuli (e.g., without an insect or other apparent biotic or abiotic cue). These findings have implications for nematode spatial distribution and suggest that group behavior is involved in nematode foraging. Published by Elsevier Ltd.

Mesoscopic Simulations of Adsorption and Association of PEO-PPO-PEO Triblock Copolymers on a Hydrophobic Surface: From Mushroom Hemisphere to Rectangle Brush.

PubMed

Song, Xianyu; Zhao, Shuangliang; Fang, Shenwen; Ma, Yongzhang; Duan, Ming

2016-11-08

The dissipative particle dynamics (DPD) method is used to investigate the adsorption behavior of PEO-PPO-PEO triblock copolymers at the liquid/solid interface. The effect of molecular architecture on the self-assembled monolayer adsorption of PEO-PPO-PEO triblock copolymers on hydrophobic surfaces is elucidated by the adsorption process, film properties, and adsorption morphologies. The adsorption thicknesses on hydrophobic surfaces and the diffusion coefficient as well as the aggregation number of Pluronic copolymers in aqueous solution observed in our simulations agree well with previous experimental and numerical observations. The radial distribution function revealed that the ability of self-assembly on hydrophobic surfaces is P123 > P84 > L64 > P105 > F127, which increased with the EO ratio of the Pluronic copolymers. Moreover, the shape parameter and the degree of anisotropy increase with increasing molecular weight and mole ratio of PO of the Pluronic copolymers. Depending on the conformation of different Pluronic copolymers, the morphology transition of three regimes on hydrophobic surfaces is present: mushroom or hemisphere, progressively semiellipsoid, and rectangle brush regimes induced by decreasing molecular weight and mole ratio of EO of Pluronic copolymers.

Microstructure of squarylium dye J aggregate films examined on the basis of optical behavior at low temperature

NASA Astrophysics Data System (ADS)

Tatsuura, Satoshi; Tian, Minquan; Furuki, Makoto; Sato, Yasuhiro; Iwasa, Izumi; Pu, Lyong Sun; Kawashima, Hitoshi; Ishikawa, Hiroshi

2002-10-01

The microstructure of a spin-coated film of squarylium dye J aggregates is examined on the basis of the measurement of the optical properties and the third-order nonlinear optical susceptibility χ(3) at low temperature. The absorption maximum of J aggregates shifted to lower energies as the film temperature decreased, while χ(3) was independent of the temperature. The latter finding indicates that the coherent length of J aggregates is confined by a structural boundary rather than by phonons; consequently, the observed peak energy shift can be due to temperature-dependent conformational change of the aggregates. The small aggregation size may contribute to the ultrahigh-speed optical response of squarylium dye J aggregates.

Thermodynamics of aggregate formation between a non-ionic polymer and ionic surfactants: An isothermal titration calorimetric study.

PubMed

Patel, Salin Gupta; Bummer, Paul M

2017-01-10

This report examines the energetics of aggregate formation between hydroxypropyl methylcellulose (HPMC) and model ionic surfactants including sodium dodecyl sulfate (SDS) at pharmaceutically relevant concentrations using the isothermal titration calorimetry (ITC) technique and a novel treatment of calorimetric data that accounts for the various species formed. The influence of molecular weight of HPMC, temperature and ionic strength of solution on the aggregate formation process was explored. The interaction between SDS and HPMC was determined to be an endothermic process and initiated at a critical aggregation concentration (CAC). The SDS-HPMC interactions were observed to be cooperative in nature and dependent on temperature and ionic strength of the solution. Molecular weight of HPMC significantly shifted the interaction parameters between HPMC and SDS such that at the highest molecular weight (HPMC K-100M;>240kDa), although the general shape of the titration curve (enthalpogram) was observed to remain similar, the critical concentration parameters (CAC, polymer saturation concentration (C sat ) and critical micelle concentration (CMC)) were significantly altered and shifted to lower concentrations of SDS. Ionic strength was also observed to influence the critical concentration parameters for the SDS-HPMC aggregation and decreased to lower SDS concentrations with increasing ionic strength for both anionic and cationic surfactant-HPMC systems. From these data, other thermodynamic parameters of aggregation such as ΔH agg ° , ΔG agg ° , H agg ° , ΔS agg ° , and ΔC p were calculated and utilized to postulate the hydrophobic nature of SDS-HPMC aggregate formation. The type of ionic surfactant head group (anionic vs. cationic i.e., dodecyltrimethylammonium bromide (DTAB)) was found to influence the strength of HPMC-surfactant interactions wherein a distinct CAC signifying the strength of HPMC-DTAB interactions was not observed. The interpretation of the microcalorimetric data at different temperatures and ionic strengths while varying properties of polymer and surfactant was a very effective tool in investigating the nature and energetics of HPMC and ionic surfactant interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of seed nuclei in glucagon aggregation using light scattering methods and field-flow fractionation

PubMed Central

Hoppe, Cindy C; Nguyen, Lida T; Kirsch, Lee E; Wiencek, John M

2008-01-01

Background Glucagon is a peptide hormone with many uses as a therapeutic agent, including the emergency treatment of hypoglycemia. Physical instability of glucagon in solution leads to problems with the manufacture, formulation, and delivery of this pharmaceutical product. Glucagon has been shown to aggregate and form fibrils and gels in vitro. Small oligomeric precursors serve to initiate and nucleate the aggregation process. In this study, these initial aggregates, or seed nuclei, are characterized in bulk solution using light scattering methods and field-flow fractionation. Results High molecular weight aggregates of glucagon were detected in otherwise monomeric solutions using light scattering techniques. These aggregates were detected upon initial mixing of glucagon powder in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon, the removal of aggregates by filtration significantly slowed the aggregation process. Field-flow fractionation was used to separate aggregates from monomeric glucagon and determine relative mass. The molar mass of the large aggregates was shown to grow appreciably over time as the glucagon solutions gelled. Conclusion The results of this study indicate that initial glucagon solutions are predominantly monomeric, but contain small quantities of large aggregates. These results suggest that the initial aggregates are seed nuclei, or intermediates which catalyze the aggregation process, even at low concentrations. PMID:18613970

Protein Aggregation and Molecular Crowding: Perspectives From Multiscale Simulations.

PubMed

Musiani, F; Giorgetti, A

2017-01-01

Cells are extremely crowded environments, thus the use of diluted salted aqueous solutions containing a single protein is too simplistic to mimic the real situation. Macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, interactions with cognate biomolecules, and pathological aggregation. The latter phenomenon typically leads to the formation of amyloid fibrils that are linked to several lethal neurodegenerative diseases, but that can also play a functional role in certain organisms. The majority of molecular simulations performed before the last few years were conducted in diluted solutions and were restricted both in the timescales and in the system dimensions by the available computational resources. In recent years, several computational solutions were developed to get close to physiological conditions. In this review we summarize the main computational techniques used to tackle the issue of protein aggregation both in a diluted and in a crowded environment. © 2017 Elsevier Inc. All rights reserved.

Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

NASA Astrophysics Data System (ADS)

Khokhlova, Maria D.; Lyubin, Eugeny V.; Zhdanov, Alexander G.; Rykova, Sophia Yu.; Sokolova, Irina A.; Fedyanin, Andrey A.

2012-02-01

Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirschner, Matthew S.; Ding, Wendu; Li, Yuxiu

In this study, we demonstrate that coherent acoustic phonons derived from plasmonic nanoparticles can modulate electronic interactions with proximal excitonic molecular species. A series of gold bipyramids with systematically varied aspect ratios and corresponding localized surface plasmon resonance energies, functionalized with a J-aggregated thiacarbocyanine dye molecule, produce two hybridized states that exhibit clear anti-crossing behavior with a Rabi splitting energy of 120 meV. In metal nanoparticles, photoexcitation generates coherent acoustic phonons that cause oscillations in the plasmon resonance energy. In the coupled system, these photo-generated oscillations alter the metal nanoparticle’s energetic contribution to the hybridized system and, as a result,more » change the coupling between the plasmon and exciton. We demonstrate that such modulations in the hybridization is consistent across a wide range of bipyramid ensembles. We also use Finite-Difference Time Domain calculations to develop a simple model describing this behavior. Lastly, such oscillatory plasmonic-excitonic nanomaterials (OPENs) offer a route to manipulate and dynamically-tune the interactions of plasmonic/excitonic systems and unlock a range of potential applications.« less

Analysis of transgenic wheat (Triticum aestivum L.) harboring a maize (Zea mays L.) gene for plastid EF-Tu: segregation pattern, expression and effects of the transgene.

PubMed

Fu, Jianming; Ristic, Zoran

2010-06-01

We previously reported that transgenic wheat (Triticum aestivum L.) carrying a maize (Zea mays L.) gene (Zmeftu1) for chloroplast protein synthesis elongation factor, EF-Tu, displays reduced thermal aggregation of leaf proteins, reduced injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation following exposure to heat stress (18 h at 45 degrees C) [Fu et al. in Plant Mol Biol 68:277-288, 2008]. In the current study, we investigated the segregation pattern and expression of the transgene Zmeftu1 and determined the grain yield of transgenic plants after exposure to a brief heat stress (18 h at 45 degrees C). We also assessed thermal aggregation of soluble leaf proteins in transgenic plants, testing the hypothesis that increased levels of EF-Tu will lead to a non-specific protection of leaf proteins against thermal aggregation. The transgenic wheat displayed a single-gene pattern of segregation of Zmeftu1. Zmeftu1 was expressed, and the transgenic plants synthesized and accumulated three anti-EF-Tu cross-reacting polypeptides of similar molecular mass but different pI, suggesting the possibility of posttranslational modification of this protein. The transgenic plants also showed better grain yield after exposure to heat stress compared with their non-transgenic counterparts. Soluble leaf proteins of various molecular masses displayed lower thermal aggregation in transgenic than in non-transgenic wheat. The results suggest that overexpression of chloroplast EF-Tu can be beneficial to wheat tolerance to heat stress. Moreover, the results also support the hypothesis that EF-Tu contributes to heat tolerance by acting as a molecular chaperone and protecting heat-labile proteins from thermal aggregation in a non-specific manner.

Simultaneous membrane interaction of amphipathic peptide monomers, self-aggregates and cargo complexes detected by fluorescence correlation spectroscopy.

PubMed

Vasconcelos, Luís; Lehto, Tõnis; Madani, Fatemeh; Radoi, Vlad; Hällbrink, Mattias; Vukojević, Vladana; Langel, Ülo

2018-02-01

Peptides able to translocate cell membranes while carrying macromolecular cargo, as cell-penetrating peptides (CPPs), can contribute to the field of drug delivery by enabling the transport of otherwise membrane impermeable molecules. Formation of non-covalent complexes between amphipathic peptides and oligonucleotides is driven by electrostatic and hydrophobic interactions. Here we investigate and quantify the coexistence of distinct molecular species in multiple equilibria, namely peptide monomer, peptide self-aggregates and peptide/oligonucleotide complexes. As a model for the complexes, we used a stearylated peptide from the PepFect family, PF14 and siRNA. PF14 has a cationic part and a lipid part, resembling some characteristics of cationic lipids. Fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) were used to detect distinct molecular entities in solution and at the plasma membrane of live cells. For that, we labeled the peptide with carboxyrhodamine 6G and the siRNA with Cyanine 5. We were able to detect fluorescent entities with diffusional properties characteristic of the peptide monomer as well as of peptide aggregates and peptide/oligonucleotide complexes. Strategies to avoid peptide adsorption to solid surfaces and self-aggregation were developed and allowed successful FCS measurements in solution and at the plasma membrane. The ratio between the detected molecular species was found to vary with pH, peptide concentration and the proximity to the plasma membrane. The present results suggest that the diverse cellular uptake mechanisms, often reported for amphipathic CPPs, might result from the synergistic effect of peptide monomers, self-aggregates and cargo complexes, distributed unevenly at the plasma membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple generations of grain aggregation in different environments preceded solar system body formation.

PubMed

Ishii, Hope A; Bradley, John P; Bechtel, Hans A; Brownlee, Donald E; Bustillo, Karen C; Ciston, James; Cuzzi, Jeffrey N; Floss, Christine; Joswiak, David J

2018-06-26

The solar system formed from interstellar dust and gas in a molecular cloud. Astronomical observations show that typical interstellar dust consists of amorphous ( a -) silicate and organic carbon. Bona fide physical samples for laboratory studies would yield unprecedented insight about solar system formation, but they were largely destroyed. The most likely repositories of surviving presolar dust are the least altered extraterrestrial materials, interplanetary dust particles (IDPs) with probable cometary origins. Cometary IDPs contain abundant submicron a- silicate grains called GEMS (glass with embedded metal and sulfides), believed to be carbon-free. Some have detectable isotopically anomalous a- silicate components from other stars, proving they are preserved dust inherited from the interstellar medium. However, it is debated whether the majority of GEMS predate the solar system or formed in the solar nebula by condensation of high-temperature (>1,300 K) gas. Here, we map IDP compositions with single nanometer-scale resolution and find that GEMS contain organic carbon. Mapping reveals two generations of grain aggregation, the key process in growth from dust grains to planetesimals, mediated by carbon. GEMS grains, some with a- silicate subgrains mantled by organic carbon, comprise the earliest generation of aggregates. These aggregates (and other grains) are encapsulated in lower-density organic carbon matrix, indicating a second generation of aggregation. Since this organic carbon thermally decomposes above ∼450 K, GEMS cannot have accreted in the hot solar nebula, and formed, instead, in the cold presolar molecular cloud and/or outer protoplanetary disk. We suggest that GEMS are consistent with surviving interstellar dust, condensed in situ, and cycled through multiple molecular clouds. Copyright © 2018 the Author(s). Published by PNAS.

Microscopic analysis of protein oxidative damage: effect of carbonylation on structure, dynamics, and aggregability of villin headpiece.

PubMed

Petrov, Drazen; Zagrovic, Bojan

2011-05-11

One of the most important irreversible oxidative modifications of proteins is carbonylation, the process of introducing a carbonyl group in reaction with reactive oxygen species. Notably, carbonylation increases with the age of cells and is associated with the formation of intracellular protein aggregates and the pathogenesis of age-related disorders such as neurodegenerative diseases and cancer. However, it is still largely unclear how carbonylation affects protein structure, dynamics, and aggregability at the atomic level. Here, we use classical molecular dynamics simulations to study structure and dynamics of the carbonylated headpiece domain of villin, a key actin-organizing protein. We perform an exhaustive set of molecular dynamics simulations of a native villin headpiece together with every possible combination of carbonylated versions of its seven lysine, arginine, and proline residues, quantitatively the most important carbonylable amino acids. Surprisingly, our results suggest that high levels of carbonylation, far above those associated with cell death in vivo, may be required to destabilize and unfold protein structure through the disruption of specific stabilizing elements, such as salt bridges or proline kinks, or tampering with the hydrophobic effect. On the other hand, by using thermodynamic integration and molecular hydrophobicity potential approaches, we quantitatively show that carbonylation of hydrophilic lysine and arginine residues is equivalent to introducing hydrophobic, charge-neutral mutations in their place, and, by comparison with experimental results, we demonstrate that this by itself significantly increases the intrinsic aggregation propensity of both structured, native proteins and their unfolded states. Finally, our results provide a foundation for a novel experimental strategy to study the effects of carbonylation on protein structure, dynamics, and aggregability using site-directed mutagenesis. © 2011 American Chemical Society

Describing Myxococcus xanthus Aggregation Using Ostwald Ripening Equations for Thin Liquid Films

PubMed Central

Bahar, Fatmagül; Pratt-Szeliga, Philip C.; Angus, Stuart; Guo, Jiaye; Welch, Roy D.

2014-01-01

When starved, a swarm of millions of Myxococcus xanthus cells coordinate their movement from outward swarming to inward coalescence. The cells then execute a synchronous program of multicellular development, arranging themselves into dome shaped aggregates. Over the course of development, about half of the initial aggregates disappear, while others persist and mature into fruiting bodies. This work seeks to develop a quantitative model for aggregation that accurately simulates which will disappear and which will persist. We analyzed time-lapse movies of M. xanthus development, modeled aggregation using the equations that describe Ostwald ripening of droplets in thin liquid films, and predicted the disappearance and persistence of aggregates with an average accuracy of 85%. We then experimentally validated a prediction that is fundamental to this model by tracking individual fluorescent cells as they moved between aggregates and demonstrating that cell movement towards and away from aggregates correlates with aggregate disappearance. Describing development through this model may limit the number and type of molecular genetic signals needed to complete M. xanthus development, and it provides numerous additional testable predictions. PMID:25231319

Exploring the role of hydration and confinement in the aggregation of amyloidogenic peptides Aβ16-22 and Sup357-13 in AOT reverse micelles

NASA Astrophysics Data System (ADS)

Martinez, Anna Victoria; Małolepsza, Edyta; Rivera, Eva; Lu, Qing; Straub, John E.

2014-12-01

Knowledge of how intermolecular interactions of amyloid-forming proteins cause protein aggregation and how those interactions are affected by sequence and solution conditions is essential to our understanding of the onset of many degenerative diseases. Of particular interest is the aggregation of the amyloid-β (Aβ) peptide, linked to Alzheimer's disease, and the aggregation of the Sup35 yeast prion peptide, which resembles the mammalian prion protein linked to spongiform encephalopathies. To facilitate the study of these important peptides, experimentalists have identified small peptide congeners of the full-length proteins that exhibit amyloidogenic behavior, including the KLVFFAE sub-sequence, Aβ16-22, and the GNNQQNY subsequence, Sup357-13. In this study, molecular dynamics simulations were used to examine these peptide fragments encapsulated in reverse micelles (RMs) in order to identify the fundamental principles that govern how sequence and solution environment influence peptide aggregation. Aβ16-22 and Sup357-13 are observed to organize into anti-parallel and parallel β-sheet arrangements. Confinement in the sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelles is shown to stabilize extended peptide conformations and enhance peptide aggregation. Substantial fluctuations in the reverse micelle shape are observed, in agreement with earlier studies. Shape fluctuations are found to facilitate peptide solvation through interactions between the peptide and AOT surfactant, including direct interaction between non-polar peptide residues and the aliphatic surfactant tails. Computed amide I IR spectra are compared with experimental spectra and found to reflect changes in the peptide structures induced by confinement in the RM environment. Furthermore, examination of the rotational anisotropy decay of water in the RM demonstrates that the water dynamics are sensitive to the presence of peptide as well as the peptide sequence. Overall, our results demonstrate that the RM is a complex confining environment where substantial direct interaction between the surfactant and peptides plays an important role in determining the resulting ensemble of peptide conformations. By extension the results suggest that similarly complex sequence-dependent interactions may determine conformational ensembles of amyloid-forming peptides in a cellular environment.

Synthesis and characterization of novel thermoplastic elastomers employing polyhedral oligomeric silsesquioxane physical crosslinks

NASA Astrophysics Data System (ADS)

Seurer, Bradley

Polyhedral oligomeric silsesquioxanes (POSS) are molecularly precise isotropic particles with average diameters of 1-2 nm. A typical T 8 POSS nanoparticle has an inorganic Si8O12 core surrounded by eight aliphatic or aromatic groups attached to the silicon vertices of the polyhedron promoting solubility in conventional solvents. Previously, efficient synthetic methods have been developed whereby one of the aliphatic groups on the periphery is substituted by a functional group capable of undergoing either homo- or copolymerization. In the current investigations, preparative methods for the chemical incorporation of POSS macromonomers in a series elastomers have been developed. Analysis of the copolymers using WAXD reveals that pendant POSS groups off the polymer backbones aggregate, and can crystallize as nanocrystals. From both line-broadening of the diffraction maxima, and also the oriented diffraction in a drawn material, the individual POSS sub-units are crystallizing as anisotropically shaped crystallites. The formation of POSS particle aggregation is strongly dependent on the nature of the polymeric matrix and the POSS peripheral group. X-ray studies show aggregation of POSS in ethylene-propylene elastomers occurred only with a phenyl periphery, whereas POSS particles with isobutyl and ethyl peripheries disperse within the polymer matrix. By altering the polymer matrix to one containing chain repulsive fluorine units, aggregation is observed with both the phenyl and isobutyl peripheries. Altering the polymer chain to poly(dimethylcyclooctadiene), POSS aggregates with isobutyl, ethyl, cyclopentyl, and phenyl peripheries. The formation of POSS nanocrystals increases the mechanical properties of these novel thermoplastic elastomers, including an increase in the tensile storage modulus and formation of a rubbery plateau region. Tensile tests of these elastomers show an increase in elastic modulus with increasing POSS loading. The elongation at break was as high as 720%. Cyclic tensile test show some hysteresis of the elastomers. However, the curves show Mullins effect behavior, commonly seen in elastomers. Elastomers with POSS dispersion, however, show poor mechanical properties. These results demonstrate the novel material property gains by the incorporation and aggregation of POSS in thermoplastic elastomers, as well as the influence of the POSS periphery.

Significance of Interactions of Low Molecular Weight Crystallin Fragments in Lens Aging and Cataract Formation*

PubMed Central

Santhoshkumar, Puttur; Udupa, Padmanabha; Murugesan, Raju; Sharma, K. Krishna

2008-01-01

Analysis of aged and cataract lenses shows the presence of increased amounts of crystallin fragments in the high molecular weight aggregates of water-soluble and water-insoluble fractions. However, the significance of accumulation and interaction of low molecular weight crystallin fragments in aging and cataract development is not clearly understood. In this study, 23 low molecular mass (<3.5-kDa) peptides in the urea-soluble fractions of young, aged, and aged cataract human lenses were identified by mass spectroscopy. Two peptides, αB-(1–18) (MDIAIHHPWIRRPFFPFH) and βA3/A1-(59–74) (SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, γS-(167–178) (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact α-, β-, and γ-crystallins and alcohol dehydrogenase, a protein used in aggregation studies. Interaction of αB-(1–18) and βA3/A1-(59–74) peptides increased the scattering of light by β- and γ-crystallin and alcohol dehydrogenase. The ability of α-crystallin subunits to function as molecular chaperones was significantly reduced by interaction with αB-(1–18) and βA3/A1-(59–74) peptides, whereas γS peptide had no effect on chaperone-like activity of α-crystallin. The βA3/A1-(59–74 peptide caused a 5.64-fold increase in αB-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in αB-(1–18) and βA3/A1-(59–74) peptides abolished their ability to induce crystallin aggregation and light scattering. Our study suggests that interaction of crystallin-derived peptides with intact crystallins could be a key event in age-related protein aggregation in lens and cataractogenesis. PMID:18227073

High-molecular weight Aβ oligomers and protofibrils are the predominant Aβ species in the native soluble protein fraction of the AD brain

PubMed Central

Upadhaya, Ajeet Rijal; Lungrin, Irina; Yamaguchi, Haruyasu; Fändrich, Marcus; Thal, Dietmar Rudolf

2012-01-01

Abstract Alzheimer’s disease (AD) is characterized by the aggregation and deposition of amyloid β protein (Aβ) in the brain. Soluble Aβ oligomers are thought to be toxic. To investigate the predominant species of Aβ protein that may play a role in AD pathogenesis, we performed biochemical analysis of AD and control brains. Sucrose buffer-soluble brain lysates were characterized in native form using blue native (BN)-PAGE and also in denatured form using SDS-PAGE followed by Western blot analysis. BN-PAGE analysis revealed a high-molecular weight smear (>1000 kD) of Aβ42-positive material in the AD brain, whereas low-molecular weight and monomeric Aβ species were not detected. SDS-PAGE analysis, on the other hand, allowed the detection of prominent Aβ monomer and dimer bands in AD cases but not in controls. Immunoelectron microscopy of immunoprecipitated oligomers and protofibrils/fibrils showed spherical and protofibrillar Aβ-positive material, thereby confirming the presence of high-molecular weight Aβ (hiMWAβ) aggregates in the AD brain. In vitro analysis of synthetic Aβ40- and Aβ42 preparations revealed Aβ fibrils, protofibrils, and hiMWAβ oligomers that were detectable at the electron microscopic level and after BN-PAGE. Further, BN-PAGE analysis exhibited a monomer band and less prominent low-molecular weight Aβ (loMWAβ) oligomers. In contrast, SDS-PAGE showed large amounts of loMWAβ but no hiMWAβ40 and strikingly reduced levels of hiMWAβ42. These results indicate that hiMWAβ aggregates, particularly Aβ42 species, are most prevalent in the soluble fraction of the AD brain. Thus, soluble hiMWAβ aggregates may play an important role in the pathogenesis of AD either independently or as a reservoir for release of loMWAβ oligomers. PMID:21418518

Pragmatic precision oncology: the secondary uses of clinical tumor molecular profiling.

PubMed

Rioth, Matthew J; Thota, Ramya; Staggs, David B; Johnson, Douglas B; Warner, Jeremy L

2016-07-01

Precision oncology increasingly utilizes molecular profiling of tumors to determine treatment decisions with targeted therapeutics. The molecular profiling data is valuable in the treatment of individual patients as well as for multiple secondary uses. To automatically parse, categorize, and aggregate clinical molecular profile data generated during cancer care as well as use this data to address multiple secondary use cases. A system to parse, categorize and aggregate molecular profile data was created. A naÿve Bayesian classifier categorized results according to clinical groups. The accuracy of these systems were validated against a published expertly-curated subset of molecular profiling data. Following one year of operation, 819 samples have been accurately parsed and categorized to generate a data repository of 10,620 genetic variants. The database has been used for operational, clinical trial, and discovery science research. A real-time database of molecular profiling data is a pragmatic solution to several knowledge management problems in the practice and science of precision oncology. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In Search for Pheromone Receptors: Certain Members of the Odorant Receptor Family in the Desert Locust Schistocerca gregaria (Orthoptera: Acrididae) Are Co-expressed with SNMP1.

PubMed

Pregitzer, Pablo; Jiang, Xingcong; Grosse-Wilde, Ewald; Breer, Heinz; Krieger, Jürgen; Fleischer, Joerg

2017-01-01

Under given environmental conditions, the desert locust ( Schistocera gregaria ) forms destructive migratory swarms of billions of animals, leading to enormous crop losses in invaded regions. Swarm formation requires massive reproduction as well as aggregation of the animals. Pheromones that are detected via the olfactory system have been reported to control both reproductive and aggregation behavior. However, the molecular basis of pheromone detection in the antennae of Schistocerca gregaria is unknown. As an initial step to disclose pheromone receptors, we sequenced the antennal transcriptome of the desert locust. By subsequent bioinformatical approaches, 119 distinct nucleotide sequences encoding candidate odorant receptors (ORs) were identified. Phylogenetic analyses employing the identified ORs from Schistocerca gregaria (SgreORs) and OR sequences from the related species Locusta migratoria revealed a group of locust ORs positioned close to the root, i.e. at a basal site in a phylogenetic tree. Within this particular OR group (termed basal or b-OR group), the locust OR sequences were strictly orthologous, a trait reminiscent of pheromone receptors from lepidopteran species. In situ hybridization experiments with antennal tissue demonstrated expression of b-OR types from Schistocerca gregaria in olfactory sensory neurons (OSNs) of either sensilla trichodea or sensilla basiconica, both of which have been reported to respond to pheromonal substances. More importantly, two-color fluorescent in situ hybridization experiments showed that most b-OR types were expressed in cells co-expressing the "sensory neuron membrane protein 1" (SNMP1), a marker indicative of pheromone-sensitive OSNs in insects. Analyzing the expression of a larger number of SgreOR types outside the b-OR group revealed that only a few of them were co-expressed with SNMP1. In summary, we have identified several candidate pheromone receptors from Schistocerca gregaria that could mediate responses to pheromones implicated in controlling reproduction and aggregation behavior.

Micelle depletion-induced vs. micelle-mediated aggregation in nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ray, D., E-mail: debes.phys@gmail.com; Aswal, V. K.

2015-06-24

The phase behavior anionic silica nanoparticle (Ludox LS30) with non-ionic surfactants decaethylene glycol monododecylether (C12E10) and cationic dodecyltrimethyl ammonium bromide (DTAB) in aqueous electrolyte solution has been studied by small-angle neutron scattering (SANS). The measurements have been carried out for fixed concentrations of nanoparticle (1 wt%), surfactants (1 wt%) and electrolyte (0.1 M NaCl). Each of these nanoparticle–surfactant systems has been examined for different contrast conditions where individual components (nanoparticle or surfactant) are made visible. It is observed that the nanoparticle-micelle system in both the cases lead to the aggregation of nanoparticles. The aggregation is found to be micelle depletion-inducedmore » for C12E10 whereas micelle-mediated aggregation for DTAB. Interestingly, it is also found that phase behavior of mixed surfactant (C12E10 + DTAB) system is similar to that of C12E10 (unlike DTAB) micelles with nanoparticles.« less

Direct comparisons of X-ray scattering and atomistic molecular dynamics simulations for precise acid copolymers and ionomers

DOE PAGES

Buitrago, C. Francisco; Bolintineanu, Dan; Seitz, Michelle E.; ...

2015-02-09

Designing acid- and ion-containing polymers for optimal proton, ion, or water transport would benefit profoundly from predictive models or theories that relate polymer structures with ionomer morphologies. Recently, atomistic molecular dynamics (MD) simulations were performed to study the morphologies of precise poly(ethylene-co-acrylic acid) copolymer and ionomer melts. Here, we present the first direct comparisons between scattering profiles, I(q), calculated from these atomistic MD simulations and experimental X-ray data for 11 materials. This set of precise polymers has spacers of exactly 9, 15, or 21 carbons between acid groups and has been partially neutralized with Li, Na, Cs, or Zn. Inmore » these polymers, the simulations at 120 °C reveal ionic aggregates with a range of morphologies, from compact, isolated aggregates (type 1) to branched, stringy aggregates (type 2) to branched, stringy aggregates that percolate through the simulation box (type 3). Excellent agreement is found between the simulated and experimental scattering peak positions across all polymer types and aggregate morphologies. The shape of the amorphous halo in the simulated I(q) profile is in excellent agreement with experimental I(q). We found that the modified hard-sphere scattering model fits both the simulation and experimental I(q) data for type 1 aggregate morphologies, and the aggregate sizes and separations are in agreement. Given the stringy structure in types 2 and 3, we develop a scattering model based on cylindrical aggregates. Both the spherical and cylindrical scattering models fit I(q) data from the polymers with type 2 and 3 aggregates equally well, and the extracted aggregate radii and inter- and intra-aggregate spacings are in agreement between simulation and experiment. Furthermore, these dimensions are consistent with real-space analyses of the atomistic MD simulations. By combining simulations and experiments, the ionomer scattering peak can be associated with the average distance between branches of type 2 or 3 aggregates. Furthermore, this direct comparison of X-ray scattering data to the atomistic MD simulations is a substantive step toward providing a comprehensive, predictive model for ionomer morphology, gives substantial support for this atomistic MD model, and provides new credibility to the presence of stringy, branched, and percolated ionic aggregates in precise ionomer melts.« less

Molecular dynamics shows that ion pairing and counterion anchoring control the properties of triflate micelles: a comparison with triflate at the air/water interface.

PubMed

Lima, Filipe S; Chaimovich, Hernan; Cuccovia, Iolanda M; Horinek, Dominik

2014-02-11

Micellar properties of dodecyltrimethylammonium triflate (DTA-triflate, DTATf) are very different from those of DTA-bromide (DTAB). DTATf aggregates show high aggregation numbers (Nagg), low degree of counterion dissociation (α), disk-like shape, high packing, ordering, and low hydration. These micellar properties and the low surface tension of NaTf aqueous solutions point to a high affinity of Tf(-) to the micellar and air/water interfaces. Although the micellar properties of DTATf are well defined, the source of the Tf(-) effect upon the DTA aggregates is unclear. Molecular dynamics (MD) simulations of Tf(-) (and Br(-)) at the air/water interface and as counterion of a DTA aggregate were performed to clarify the nature of Tf(-) preferences for these interfaces. The effect of NaTf or NaBr on surface tension calculated from MD simulations agreed with the reported experimental values. From the MD simulations a high affinity of Tf(-) toward the interface, which occurred in a specific orientation, was calculated. The micellar properties calculated from the MD simulations for DTATf and DTAB were consistent with experimental data: in MD simulations, the DTATf aggregate was more ordered, packed, and dehydrated than the DTAB aggregate. The Tf(-)/alkyltrimethylammonium interaction energies, calculated from the MD simulations, suggested ion pair formation at the micellar interface, stabilized by the preferential orientation of the adsorbed Tf(-) at the micellar interface.

Rosuvastatin ameliorates cognitive impairment in rats fed with high-salt and cholesterol diet via inhibiting acetylcholinesterase activity and amyloid beta peptide aggregation.

PubMed

Husain, I; Akhtar, M; Abdin, M Zainul; Islamuddin, M; Shaharyar, M; Najmi, A K

2018-04-01

Amyloid beta (Aβ) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aβ 1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ 1-42 aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aβ 1-42 peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aβ 1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.

In silico engineering of aggregation-prone recombinant proteins for substrate recognition by the chaperonin GroEL.

PubMed

Kumar, Vipul; Punetha, Ankita; Sundar, Durai; Chaudhuri, Tapan K

2012-01-01

Molecular chaperones appear to have been evolved to facilitate protein folding in the cell through entrapment of folding intermediates on the interior of a large cavity formed between GroEL and its co-chaperonin GroES. They bind newly synthesized or non-native polypeptides through hydrophobic interactions and prevent their aggregation. Some proteins do not interact with GroEL, hence even though they are aggregation prone, cannot be assisted by GroEL for their folding. In this study, we have attempted to engineer these non-substrate proteins to convert them as the substrate for GroEL, without compromising on their function. We have used a computational biology approach to generate mutants of the selected proteins by selectively mutating residues in the hydrophobic patch, similar to GroES mobile loop region that are responsible for interaction with GroEL, and compared with the wild counterparts for calculation of their instability and aggregation propensities. The energies of the newly designed mutants were computed through molecular dynamics simulations. We observed increased aggregation propensity of some of the mutants formed after replacing charged amino acid residues with hydrophobic ones in the well defined hydrophobic patch, raising the possibility of their binding ability to GroEL. The newly generated mutants may provide potential substrates for Chaperonin GroEL, which can be experimentally generated and tested for their tendency of aggregation, interactions with GroEL and the possibility of chaperone-assisted folding to produce functional proteins.

Molecular dynamics simulation of β₂-microglobulin in denaturing and stabilizing conditions.

PubMed

Fogolari, Federico; Corazza, Alessandra; Varini, Nicola; Rotter, Matteo; Gumral, Devrim; Codutti, Luca; Rennella, Enrico; Viglino, Paolo; Bellotti, Vittorio; Esposito, Gennaro

2011-03-01

β₂-Microglobulin has been a model system for the study of fibril formation for 20 years. The experimental study of β₂-microglobulin structure, dynamics, and thermodynamics in solution, at atomic detail, along the pathway leading to fibril formation is difficult because the onset of disorder and aggregation prevents signal resolution in Nuclear Magnetic Resonance experiments. Moreover, it is difficult to characterize conformers in exchange equilibrium. To gain insight (at atomic level) on processes for which experimental information is available at molecular or supramolecular level, molecular dynamics simulations have been widely used in the last decade. Here, we use molecular dynamics to address three key aspects of β₂-microglobulin, which are known to be relevant to amyloid formation: (1) 60 ns molecular dynamics simulations of β₂-microglobulin in trifluoroethanol and in conditions mimicking low pH are used to study the behavior of the protein in environmental conditions that are able to trigger amyloid formation; (2) adaptive biasing force molecular dynamics simulation is used to force cis-trans isomerization at Proline 32 and to calculate the relative free energy in the folded and unfolded state. The native-like trans-conformer (known as intermediate 2 and determining the slow phase of refolding), is simulated for 10 ns, detailing the possible link between cis-trans isomerization and conformational disorder; (3) molecular dynamics simulation of highly concentrated doxycycline (a molecule able to suppress fibril formation) in the presence of β₂-microglobulin provides details of the binding modes of the drug and a rationale for its effect. Copyright © 2010 Wiley-Liss, Inc.

The Macromolecular Concept and the Origins of Molecular Biology

ERIC Educational Resources Information Center

Olby, Robert

1970-01-01

Traces the origins of molecular biology to the work of 19th century biophysicists, ultrastructurists and collodial chemists. The development of the Aggregate Theory,and its overthrow by the Macromolecule Concept is described. Research in molecular genetics in the pre-second world war period, and the effects of the war on it, are briefly reviewed.…

The aggregation behavior and interactions of yak milk protein under thermal treatment.

PubMed

Wang, T T; Guo, Z W; Liu, Z P; Feng, Q Y; Wang, X L; Tian, Q; Ren, F Z; Mao, X Y

2016-08-01

The aggregation behavior and interactions of yak milk protein were investigated after heat treatments. Skim yak milk was heated at temperatures in the range of 65 to 95°C for 10 min. The results showed that the whey proteins in yak milk were denatured after heat treatment, especially at temperatures higher than 85°C. Sodium dodecyl sulfate-PAGE analysis indicated that heat treatment induced milk protein denaturation accompanied with aggregation to a certain extent. When the heating temperature was 75 and 85°C, the aggregation behavior of yak milk proteins was almost completely due to the formation of disulfide bonds, whereas denatured α-lactalbumin and β-lactoglobulin interacted with κ-casein. When yak milk was heated at 85 and 95°C, other noncovalent interactions were found between proteins including hydrophobic interactions. The particle size distributions and microstructures demonstrated that the heat stability of yak milk proteins was significantly lowered by heat treatment. When yak milk was heated at 65 and 75°C, no obvious changes were found in the particle size distribution and microstructures in yak milk. When the temperature was 85 and 95°C, the particle size distribution shifted to larger size trend and aggregates were visible in the heated yak milk. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Aggregation Behavior and a Putative Aggregation Pheromone in Sugar Beet Root Maggot Flies (Diptera: Ulidiidae)

PubMed Central

Emmert, Susan Y.; Tindall, Kelly; Ding, Hongjian; Boetel, Mark A.; Rajabaskar, D.; Eigenbrode, Sanford D.

2017-01-01

Male-biased aggregations of sugar beet root maggot, Tetanops myopaeformis (Röder) (Diptera: Ulidiidae), flies were observed on utility poles near sugar beet (Beta vulgaris L. [Chenopodiaceae]) fields in southern Idaho; this contrasts with the approximately equal sex ratio typically observed within fields. Peak observation of mating pairs coincided with peak diurnal abundance of flies. Volatiles released by individual male and female flies were sampled from 08:00 to 24:00 hours in the laboratory using solid-phase microextraction and analyzed using gas chromatography/mass spectrometry (GC/MS). Eleven compounds were uniquely detected from males. Three of these compounds (2-undecanol, 2-decanol, and sec-nonyl acetate) were detected in greater quantities during 12:00–24:00 hours than during 08:00–12:00 hours. The remaining eight compounds uniquely detected from males did not exhibit temporal trends in release. Both sexes produced 2-nonanol, but males produced substantially higher (ca. 80-fold) concentrations of this compound than females, again peaking after 12:00 hours. The temporal synchrony among male aggregation behavior, peak mating rates, and release of certain volatile compounds by males suggest that T. myopaeformis flies exhibit lekking behavior and produce an associated pheromone. Field assays using synthetic blends of the putative aggregation pheromone showed evidence of attraction in both females and males. PMID:28423428

Cationic PAMAM Dendrimers Aggressively Initiate Blood Clot Formation

PubMed Central

Jones, Clinton F.; Campbell, Robert A.; Brooks, Amanda E.; Assemi, Shoeleh; Tadjiki, Soheyl; Thiagarajan, Giridhar; Mulcock, Cheyanne; Weyrich, Andrew S.; Brooks, Benjamin D.; Ghandehari, Hamidreza; Grainger, David W.

2012-01-01

Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood contacting applications, amine-terminated dendrimers have recently been shown to activate platelets and cause a fatal, disseminated intravascular coagulation (DIC)-like condition in mice and rats. We here demonstrate that, upon addition to blood, cationic G7 PAMAM dendrimers induce fibrinogen aggregation, which may contribute to the in vivo DIC-like phenomenon. We demonstrate that amine-terminated dendrimers act directly on fibrinogen in a thrombin-independent manner to generate dense, high-molecular-weight fibrinogen aggregates with minimal fibrin fibril formation. In addition, we hypothesize this clot-like behavior is likely mediated through electrostatic interactions between the densely charged cationic dendrimer surface and negatively charged fibrinogen domains. Interestingly, cationic dendrimers also induced aggregation of albumin, suggesting that many negatively charged blood proteins may be affected by cationic dendrimers. To investigate this further, zebrafish embryos (ZFE) were employed to more specifically determine the speed of this phenomenon and the pathway- and dose-dependency of the resulting vascular occlusion phenotype. These novel findings show that G7 PAMAM dendrimers significantly and adversely impact many blood components to produce rapid coagulation and strongly suggest that these effects are independent of classic coagulation mechanisms. These results also strongly suggest the need to fully characterize amine-terminated PAMAM dendrimers in regards to their adverse effects on both coagulation and platelets, which may contribute to blood toxicity. PMID:23062017

[Influence of genetic factors on human sexual orientation. Review].

PubMed

Rodríguez-Larralde, Alvaro; Paradisi, Irene

2009-09-01

Human sexual orientation is a complex trait, influenced by several genes, experiential and sociocultural factors. These elements interact and produce a typical pattern of sexual orientation towards the opposite sex. Some exceptions exist, like bisexuality and homosexuality, which seem to be more frequent in males than females. Traditional methods for the genetic study of behavior multifactorial characteristics consist in detecting the presence of familial aggregation. In order to identify the importance of genetic and environmental factors in this aggregation, the concordance of the trait for monozygotic and dizygotic twins and for adopted sibs, reared together and apart, is compared. These types of studies have shown that familial aggregation is stronger for male than for female homosexuality. Based on the threshold method for multifactorial traits, and varying the frequency of homosexuality in the population between 4 and 10%, heritability estimates between 0.27 and 0.76 have been obtained. In 1993, linkage between homosexuality and chromosomal region Xq28 based on molecular approaches was reported. Nevertheless, this was not confirmed in later studies. Recently, a wide search of the genome has given significant or close to significant linkage values with regions 7q36, 8p12 and 10q26, which need to be studied more closely. Deviation in the proportion of X chromosome inactivation in mothers of homosexuals seems to favor the presence of genes related with sexual orientation in this chromosome. There is still much to be known about the genetics of human homosexuality.

C{sub 60}-dyad aggregates: Self-organized structures in aqueous solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guskova, O. A., E-mail: guskova@ipfdd.de, E-mail: s.raovaranasi@uq.edu.au; Varanasi, S. R., E-mail: guskova@ipfdd.de, E-mail: s.raovaranasi@uq.edu.au; Sommer, J.-U.

2014-10-14

Extensive full-atomistic molecular dynamics simulations are performed to study the self-organization of C{sub 60}-fullerene dyad molecules in water, namely phenyl-C{sub 61}-butyric acid methyl ester and fulleropyrrolidines, which have two elements of ordering, the hydrophobic fullerene cage and the hydrophilic/ionic group. While pristine fullerene or phenyl-C{sub 61}-butyric acid methyl ester forms spherical droplets in order to minimize the surface tension, the amphiphilic nature of charged solute molecules leads to the formation of supramolecular assemblies having cylindrical shape driven by charge repulsion between the ionic groups located on the surface of the aggregates. We show that formation of non-spherical micelles is themore » geometrical consequence if the fullerene derivatives are considered as surfactants where the ionized groups are only hydrophilic unit. The agglomeration behavior of fullerenes is evaluated by determining sizes of the clusters, solvent accessible surface areas, and shape parameters. By changing the size of the counterions from chloride over iodide to perchlorate we find a thickening of the cylinder-like structures which can be explained by stronger condensation of larger ions and thus partial screening of the charge repulsion on the cluster surface. The reason for the size dependence of counterion condensation is the formation of a stronger hydration shell in case of small ions which in turn are repelled from the fullerene aggregates. Simulations are also in good agreement with the experimentally observed morphologies of decorated C{sub 60}-nanoparticles.« less

Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice*

PubMed Central

Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Teng, Edmond; Hu, Shuxin; Chen, Ping-Ping; Maiti, Panchanan; Teter, Bruce; Cole, Greg M.; Frautschy, Sally A.

2013-01-01

The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected. PMID:23264626

Aggregation of flexible polyelectrolytes: Phase diagram and dynamics.

PubMed

Tom, Anvy Moly; Rajesh, R; Vemparala, Satyavani

2017-10-14

Similarly charged polymers in solution, known as polyelectrolytes, are known to form aggregated structures in the presence of oppositely charged counterions. Understanding the dependence of the equilibrium phases and the dynamics of the process of aggregation on parameters such as backbone flexibility and charge density of such polymers is crucial for insights into various biological processes which involve biological polyelectrolytes such as protein, DNA, etc. Here, we use large-scale coarse-grained molecular dynamics simulations to obtain the phase diagram of the aggregated structures of flexible charged polymers and characterize the morphology of the aggregates as well as the aggregation dynamics, in the presence of trivalent counterions. Three different phases are observed depending on the charge density: no aggregation, a finite bundle phase where multiple small aggregates coexist with a large aggregate and a fully phase separated phase. We show that the flexibility of the polymer backbone causes strong entanglement between charged polymers leading to additional time scales in the aggregation process. Such slowing down of the aggregation dynamics results in the exponent, characterizing the power law decay of the number of aggregates with time, to be dependent on the charge density of the polymers. These results are contrary to those obtained for rigid polyelectrolytes, emphasizing the role of backbone flexibility.

Impact of Cavitation, High Shear Stress and Air/Liquid Interfaces on Protein Aggregation.

PubMed

Duerkop, Mark; Berger, Eva; Dürauer, Astrid; Jungbauer, Alois

2018-03-25

The reported impact of shear stress on protein aggregation has been contradictory. At high shear rates, the occurrence of cavitation or entrapment of air is reasonable and their effects possibly misattributed to shear stress. Nine different proteins (α-lactalbumin, two antibodies, fibroblast growth factor 2, granulocyte colony stimulating factor [GCSF], green fluorescence protein [GFP], hemoglobin, human serum albumin, and lysozyme) are tested for their aggregation behavior on vapor/liquid interfaces generated by cavitation and compared it to the isolated effects of high shear stress and air/liquid interfaces generated by foaming. Cavitation induced the aggregation of GCSF by +68.9%, hemoglobin +4%, and human serum albumin +2.9%, compared to a control, whereas the other proteins do not aggregate. The protein aggregation behaviors of the different proteins at air/liquid interfaces are similar to cavitation, but the effect is more pronounced. Air-liquid interface induced the aggregation of GCSF by +94.5%, hemoglobin +35.5%, and human serum albumin (HSA) +31.1%. The results indicate that the sensitivity of a certain protein toward cavitation is very similar to air/liquid-induced aggregation. Hence, hydroxyl radicals cannot be seen as the driving force for protein aggregation when cavitation occurs. Further, high shear rates of up to 10 8  s -1 do not affect any of the tested proteins. Therefore, also within this study generated extremely high isolated shear rates cannot be considered to harm structural integrity when processing proteins. © 2018 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Effect of counterions on the shape, hydration, and degree of order at the interface of cationic micelles: the triflate case.

PubMed

Lima, Filipe S; Cuccovia, Iolanda M; Horinek, Dominik; Amaral, Lia Q; Riske, Karin A; Schreier, Shirley; Salinas, Roberto K; Bastos, Erick L; Pires, Paulo A R; Bozelli, José Carlos; Favaro, Denize C; Rodrigues, Ana Clara B; Dias, Luís Gustavo; El Seoud, Omar A; Chaimovich, Hernan

2013-04-02

Specific ion effects in surfactant solutions affect the properties of micelles. Dodecyltrimethylammonium chloride (DTAC), bromide (DTAB), and methanesulfonate (DTAMs) micelles are typically spherical, but some organic anions can induce shape or phase transitions in DTA(+) micelles. Above a defined concentration, sodium triflate (NaTf) induces a phase separation in dodecyltrimethylammonium triflate (DTATf) micelles, a phenomenon rarely observed in cationic micelles. This unexpected behavior of the DTATf/NaTf system suggests that DTATf aggregates have unusual properties. The structural properties of DTATf micelles were analyzed by time-resolved fluorescence quenching, small-angle X-ray scattering, nuclear magnetic resonance, and electron paramagnetic resonance and compared with those of DTAC, DTAB, and DTAMs micelles. Compared to the other micelle types, the DTATf micelles had a higher average number of monomers per aggregate, an uncommon disk-like shape, smaller interfacial hydration, and restricted monomer chain mobility. Molecular dynamic simulations supported these observations. Even small water-soluble salts can profoundly affect micellar properties; our data demonstrate that the -CF3 group in Tf(-) was directly responsible for the observed shape changes by decreasing interfacial hydration and increasing the degree of order of the surfactant chains in the DTATf micelles.

Role of Different Alpha-Synuclein Strains in Synucleinopathies, Similarities with other Neurodegenerative Diseases

PubMed Central

Melki, Ronald

2015-01-01

Abstract Misfolded protein aggregates are the hallmark of several neurodegenerative diseases in humans. The main protein constituent of these aggregates and the regions within the brain that are affected differ from one neurodegenerative disorder to another. A plethora of reports suggest that distinct diseases have in common the ability of protein aggregates to spread and amplify within the central nervous system. This review summarizes briefly what is known about the nature of the protein aggregates that are infectious and the reason they are toxic to cells. The chameleon property of polypeptides which aggregation into distinct high-molecular weight assemblies is associated to different diseases, in particular, that of alpha-synuclein which aggregation is the hallmark of distinct synucleinopathies, is discussed. Finally, strategies targeting the formation and propagation of structurally distinct alpha-synuclein assemblies associated to different synucleinopathies are presented and their therapeutic and diagnostic potential is discussed. PMID:25757830

Hydrogen-bonded aggregates in precise acid copolymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lueth, Christopher A.; Bolintineanu, Dan S.; Stevens, Mark J., E-mail: msteve@sandia.gov

2014-02-07

We perform atomistic molecular dynamics simulations of melts of four precise acid copolymers, two poly(ethylene-co-acrylic acid) (PEAA) copolymers, and two poly(ethylene-co-sulfonic acid) (PESA) copolymers. The acid groups are spaced by either 9 or 21 carbons along the polymer backbones. Hydrogen bonding causes the acid groups to form aggregates. These aggregates give rise to a low wavevector peak in the structure factors, in agreement with X-ray scattering data for the PEAA materials. The structure factors for the PESA copolymers are very similar to those for the PEAA copolymers, indicating a similar distance between aggregates which depends on the spacer length butmore » not on the nature of the acid group. The PEAA copolymers are found to form more dimers and other small aggregates than do the PESA copolymers, while the PESA copolymers have both more free acid groups and more large aggregates.« less

Probing the inhibitory potency of epigallocatechin gallate against human γB-crystallin aggregation: Spectroscopic, microscopic and simulation studies

NASA Astrophysics Data System (ADS)

Chaudhury, Susmitnarayan; Dutta, Anirudha; Bag, Sudipta; Biswas, Pranandita; Das, Amit Kumar; Dasgupta, Swagata

2018-03-01

Aggregation of human ocular lens proteins, the crystallins is believed to be one of the key reasons for age-onset cataract. Previous studies have shown that human γD-crystallin forms amyloid like fibres under conditions of low pH and elevated temperature. In this article, we have investigated the aggregation propensity of human γB-crystallin in absence and presence of epigallocatechin gallate (EGCG), in vitro, when exposed to stressful conditions. We have used different spectroscopic and microscopic techniques to elucidate the inhibitory effect of EGCG towards aggregation. The experimental results have been substantiated by molecular dynamics simulation studies. We have shown that EGCG possesses inhibitory potency against the aggregation of human γB-crystallin at low pH and elevated temperature.

Protein Aggregation/Folding: The Role of Deterministic Singularities of Sequence Hydrophobicity as Determined by Nonlinear Signal Analysis of Acylphosphatase and Aβ(1–40)

PubMed Central

Zbilut, Joseph P.; Colosimo, Alfredo; Conti, Filippo; Colafranceschi, Mauro; Manetti, Cesare; Valerio, MariaCristina; Webber, Charles L.; Giuliani, Alessandro

2003-01-01

The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Aβ(1–40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features. Static and dynamic approaches were used to elucidate conditions coincident with folding vs. aggregation using comparisons with known protein secondary structure classifications, site-directed mutagenesis studies of acylphosphatase, and molecular dynamics simulations of amyloid protein, Aβ(1–40). The results suggest that a feature derived from principal component space characterized by the smoothness of singular, deterministic hydrophobicity patches plays a significant role in the conditions governing protein aggregation. PMID:14645049

GENERAL: Kinetic Behaviors of Catalysis-Driven Growth of Three-Species Aggregates on Base of Exchange-Driven Aggregations

NASA Astrophysics Data System (ADS)

Sun, Yun-Fei; Chen, Dan; Lin, Zhen-Quan; Ke, Jian-Hong

2009-06-01

We propose a solvable aggregation model to mimic the evolution of population A, asset B, and the quantifiable resource C in a society. In this system, the population and asset aggregates themselves grow through self-exchanges with the rate kernels K1(k, j) = K1kj and K2(k, j) = K2kj, respectively. The actions of the population and asset aggregations on the aggregation evolution of resource aggregates are described by the population-catalyzed monomer death of resource aggregates and asset-catalyzed monomer birth of resource aggregates with the rate kernels J1(k, j) = J1k and J2(k, j) = J2k, respectively. Meanwhile, the asset and resource aggregates conjunctly catalyze the monomer birth of population aggregates with the rate kernel I1(k, i, j) = I1kiμjη, and population and resource aggregates conjunctly catalyze the monomer birth of asset aggregates with the rate kernel I2(k, i, j) = I2kivjη. The kinetic behaviors of species A, B, and C are investigated by means of the mean-field rate equation approach. The effects of the population-catalyzed death and asset-catalyzed birth on the evolution of resource aggregates based on the self-exchanges of population and asset appear in effective forms. The coefficients of the effective population-catalyzed death and the asset-catalyzed birth are expressed as J1e = J1/K1 and J2e = J2/K2, respectively. The aggregate size distribution of C species is found to be crucially dominated by the competition between the effective death and the effective birth. It satisfies the conventional scaling form, generalized scaling form, and modified scaling form in the cases of J1e < J2e, J1e = J2e, and J1e > J2e, respectively. Meanwhile, we also find the aggregate size distributions of populations and assets both fall into two distinct categories for different parameters μ, ν, and η: (i) When μ = ν = η = 0 and μ = ν = 0, η = 1, the population and asset aggregates obey the generalized scaling forms; and (ii) When μ = ν = 1, η = 0, and μ = ν = η = 1, the population and asset aggregates experience gelation transitions at finite times and the scaling forms break down.

Self-organized huddles of rat pups modeled by simple rules of individual behavior.

PubMed

Schank, J C; Alberts, J R

1997-11-07

Starting at infancy and continuing throughout adult life, huddling is a major component of the behavioral repertoire of Norway rats (Rattus norvegicus). Huddling behavior maintains the cohesion of litters throughout early life, and in adulthood, it remains a consistent feature of social behavior of R. norvegicus. During infancy, rats have severely limited sensorimotor capabilities, and yet they are capable of aggregating and display a form of group regulatory behavior that conserves metabolic effort and augments body temperature regulation. The functions of huddling are generally understood as group adaptations, which are beyond the capabilities of the individual infant rat. We show, however, that huddling as aggregative or cohesive behavior can emerge as a self-organizing process from autonomous individuals following simple sensorimotor rules. In our model, two sets of sensorimotor parameters characterize the topotaxic responses and the dynamics of contact in 7-day-old rats. The first set of parameters are conditional probabilities of activity and inactivity given prior activity or inactivity and the second set are preferences for objects in the infant rat's environment. We found that the behavior of the model and of actual rat pups compare very favorably, demonstrating that the aggregative feature of huddling can emerge from the local sensorimotor interactions of individuals, and that complex group regulatory behaviors in infant rats may also emerge from self-organizing processes. We discuss the model and the underlying approach as a paradigm for investigating the dynamics of social interactions, group behavior, and developmental change.

Pestiferous nature, resting sites, aggregation, and host-seeking behavior of the eye fly Siphunculina funicola (Diptera: Chloropidae) in Thailand.

PubMed

Mulla, Mir S; Chansang, Uruyakorn

2007-12-01

Species of eye flies and eye gnats (Diptera: Chloropidae) are severe and persistent pests of man, domestic and wild animals, and potential vectors of pathogens. The species prevailing in the Oriental region belong to the genus Siphunculina, while those in the Neotropic and Nearctic regions belong to Liohippelates and Hippelates. These are small insects of 1-2 mm that feed on wounds, lacerations, scratches, and mucous membranes of man and higher animals. One species, Siphunculina funicola, commonly known as the Oriental eye fly, is considered the most anthropophilic in the genus, with potential involvement in the spread and mechanical transmission of infectious agents to humans and animals. Very little is known about the biology, prevalence, host-seeking, and aggregation behavior of this species in South and Southeast Asia. We initiated studies on biological aspects of this potential vector and human pest in central Thailand. The most significant findings of our study were the aggregation behaviors of S. funicola, that both sexes attack hosts, and that males outnumbered females attacking humans, dogs, and other domestic animals. They feed on wounds, scabs, lacerations, eyes, and mucous membranes. They hover around and feed on hosts during the daylight hours when host-seeking activities are more pronounced at temperatures above 25-27 degrees C under calm conditions. We noted that large masses of males and females aggregated on a variety of hanging objects such as strings, trailings, electrical lines, decorations, ropes, twines, abandoned cob webs, clothes hangers, and other hanging substrates in open shade of structures and dwellings. This behavior of eye flies brings them closer to human and animal hosts. In these aggregations, both males and females were present, with mating pairs frequently noted. In the aggregations, about 37% of the females had fully developed eggs in the rainy season, but only <1-3.6% were gravid in the hot and dry season. The average number of eggs per female was generally 42 to 44.

Spherical and hyperspherical harmonics representation of van der Waals aggregates

NASA Astrophysics Data System (ADS)

Lombardi, Andrea; Palazzetti, Federico; Aquilanti, Vincenzo; Grossi, Gaia; Albernaz, Alessandra F.; Barreto, Patricia R. P.; Cruz, Ana Claudia P. S.

2016-12-01

The representation of the potential energy surfaces of atom-molecule or molecular dimers interactions should account faithfully for the symmetry properties of the systems, preserving at the same time a compact analytical form. To this aim, the choice of a proper set of coordinates is a necessary precondition. Here we illustrate a description in terms of hyperspherical coordinates and the expansion of the intermolecular interaction energy in terms of hypersherical harmonics, as a general method for building potential energy surfaces suitable for molecular dynamics simulations of van der Waals aggregates. Examples for the prototypical case diatomic-molecule-diatomic-molecule interactions are shown.

Recent aspects of self-oscillating polymeric materials: designing self-oscillating polymers coupled with supramolecular chemistry and ionic liquid science.

PubMed

Ueki, Takeshi; Yoshida, Ryo

2014-06-14

Herein, we summarise the recent developments in self-oscillating polymeric materials based on the concepts of supramolecular chemistry, where aggregates of molecular building blocks with non-covalent bonds evolve the temporal or spatiotemporal structure. By utilising the rhythmic oscillation of the association/dissociation of molecular aggregates coupled with the redox oscillation by the BZ reaction, novel soft materials that express similar functions as those of living matter will be achieved. Further, from the viewpoint of materials science, our recent approach to prepare self-oscillating materials that operate long-term under mild conditions will be introduced.

Macromolecules Vis-a-Vis the Traditions of Chemistry

ERIC Educational Resources Information Center

Flory, Paul J.

1973-01-01

Summarizes the history of concepts concerning the molecular nature of polymers, involving the carbon chain theory, graphic formula, polycondensation, colloidal properties, polypeptide hypothesis, secondary aggregation, and Watson-Crick model. Indicates that macromolecular science should be accommodated within the discipline of molecular science…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitagawa, Norihito; Oda, Mayuko; Nobutaka, I.

Although amitriptyline has gained attention as a potent local anesthetic, recent animal studies showed that it can cause irreversible neural impairment. We hypothesized that nerve membrane disruption caused by solubilization, a common detergent property, accounted for amitriptyline neurotoxicity. We used a two-phase approach to test our hypothesis. Firstly, we determined (1) the molecular aggregation concentration of amitriptyline (2) the concentration of amitriptyline that disrupts artificial lipid membranes and (3) the concentration of amitriptyline that causes hemolysis. Secondly, we compared these levels with neurotoxic concentrations determined from assessment in a rat model of spinal anesthesia using changes in cutaneous stimulus thresholdmore » (CST). Amitriptyline concentrations that caused molecular aggregation, model membrane disruption and hemolysis were 0.46%, 0.35% and 0.3%, respectively. Animal study showed a significant increase in CST at {>=} 0.3% of amitriptyline, indicating neurological impairment. Since amitriptyline caused model membrane disruption and hemolysis at the molecular aggregation concentration, solubilization plays a role in the destruction of artificial membranes and erythrocytes. Furthermore, these concentrations are also in good agreement with the minimum concentration causing neurological injury. Therefore, while additional studies, including histopathology, are necessary to clarify this observation, amitriptyline neurotoxicity appears to be associated with its detergent nature.« less