Diffusion coefficients of Fokker-Planck equation for rotating dust grains in a fusion plasma

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

Bakhtiyari-Ramezani, M., E-mail: mahdiyeh.bakhtiyari@gmail.com; Alinejad, N., E-mail: nalinezhad@aeoi.org.ir; Mahmoodi, J., E-mail: mahmoodi@qom.ac.ir

2015-11-15

In the fusion devices, ions, H atoms, and H{sub 2} molecules collide with dust grains and exert stochastic torques which lead to small variations in angular momentum of the grain. By considering adsorption of the colliding particles, thermal desorption of H atoms and normal H{sub 2} molecules, and desorption of the recombined H{sub 2} molecules from the surface of an oblate spheroidal grain, we obtain diffusion coefficients of the Fokker-Planck equation for the distribution function of fluctuating angular momentum. Torque coefficients corresponding to the recombination mechanism show that the nonspherical dust grains may rotate with a suprathermal angular velocity.

Diffusion coefficients of Fokker-Planck equation for rotating dust grains in a fusion plasma

NASA Astrophysics Data System (ADS)

Bakhtiyari-Ramezani, M.; Mahmoodi, J.; Alinejad, N.

2015-11-01

In the fusion devices, ions, H atoms, and H2 molecules collide with dust grains and exert stochastic torques which lead to small variations in angular momentum of the grain. By considering adsorption of the colliding particles, thermal desorption of H atoms and normal H2 molecules, and desorption of the recombined H2 molecules from the surface of an oblate spheroidal grain, we obtain diffusion coefficients of the Fokker-Planck equation for the distribution function of fluctuating angular momentum. Torque coefficients corresponding to the recombination mechanism show that the nonspherical dust grains may rotate with a suprathermal angular velocity.

Optical measurement of transverse molecular diffusion in a microchannel.

PubMed Central

Kamholz, A E; Schilling, E A; Yager, P

2001-01-01

Quantitative analysis of molecular diffusion is a necessity for the efficient design of most microfluidic devices as well as an important biophysical method in its own right. This study demonstrates the rapid measurement of diffusion coefficients of large and small molecules in a microfluidic device, the T-sensor, by means of conventional epifluorescence microscopy. Data were collected by monitoring the transverse flux of analyte from a sample stream into a second stream flowing alongside it. As indicated by the low Reynolds numbers of the system (< 1), flow is laminar, and molecular transport between streams occurs only by diffusion. Quantitative determinations were made by fitting data with predictions of a one-dimensional model. Analysis was made of the flow development and its effect on the distribution of diffusing analyte using a three-dimensional modeling software package. Diffusion coefficients were measured for four fluorescently labeled molecules: fluorescein-biotin, insulin, ovalbumin, and streptavidin. The resulting values differed from accepted results by an average of 2.4%. Microfluidic system parameters can be selected to achieve accurate diffusion coefficient measurements and to optimize other microfluidic devices that rely on precise transverse transport of molecules. PMID:11259309

Viscosity, relaxation time, and dynamics within a model asphalt of larger molecules

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

Li, Derek D.; Greenfield, Michael L., E-mail: greenfield@egr.uri.edu

2014-01-21

The dynamics properties of a new “next generation” model asphalt system that represents SHRP AAA-1 asphalt using larger molecules than past models is studied using molecular simulation. The system contains 72 molecules distributed over 12 molecule types that range from nonpolar branched alkanes to polar resins and asphaltenes. Molecular weights range from 290 to 890 g/mol. All-atom molecular dynamics simulations conducted at six temperatures from 298.15 to 533.15 K provide a wealth of correlation data. The modified Kohlrausch-Williams-Watts equation was regressed to reorientation time correlation functions and extrapolated to calculate average rotational relaxation times for individual molecules. The rotational relaxationmore » rate of molecules decreased significantly with increasing size and decreasing temperature. Translational self-diffusion coefficients followed an Arrhenius dependence. Similar activation energies of ∼42 kJ/mol were found for all 12 molecules in the model system, while diffusion prefactors spanned an order of magnitude. Viscosities calculated directly at 533.15 K and estimated at lower temperatures using the Debye-Stokes-Einstein relationship were consistent with experimental data for asphalts. The product of diffusion coefficient and rotational relaxation time showed only small changes with temperature above 358.15 K, indicating rotation and translation that couple self-consistently with viscosity. At lower temperatures, rotation slowed more than diffusion.« less

Lateral diffusion and signaling of receptor for advanced glycation end-products (RAGE): a receptor involved in chronic inflammation.

PubMed

Syed, Aleem; Zhu, Qiaochu; Smith, Emily A

2018-01-01

Membrane diffusion is one of the key mechanisms in the cellular function of receptors. The signaling of receptors for advanced glycation end-products (RAGE) has been extensively studied in the context of several pathological conditions, however, very little is known about RAGE diffusion. To fill this gap, RAGE lateral diffusion is probed in native, cholesterol-depleted, and cytoskeleton-altered cellular conditions. In native GM07373 cellular conditions, RAGE has a 90% mobile fraction and an average diffusion coefficient of 0.3 μm 2 /s. When depolymerization of the actin cytoskeleton is inhibited with the small molecule jasplakinolide (Jsp), the RAGE mobile fraction and diffusion coefficient decrease by 22 and 37%, respectively. In contrast, depolymerizing the filamentous actin cytoskeleton using the small molecule cytochalasin D (CD) does not alter the RAGE diffusion properties. There is a 70 and 50% decrease in phosphorylation of extracellular signal-regulated kinase (p-ERK) when the actin cytoskeleton is disrupted by CD or Jsp, respectively, in RAGE-expressing GM07373 cells. Disrupting the actin cytoskeleton in GM07373 cells that do not express detectable amounts of RAGE results in no change in p-ERK. Cholesterol depletion results in no statistically significant change in the diffusion properties of RAGE or p-ERK. This work presents a strong link between the actin cytoskeleton and RAGE diffusion and downstream signaling, and serves to further our understanding of the factors influencing RAGE lateral diffusion.

MO-G-BRF-07: Anomalously Fast Diffusion of Carbon Nanotubes Carriers in 3D Tissue Model

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

Wang, Y; Bahng, J; Kotov, N

Purpose: We aim to investigate and understand diffusion process of carbon nanotubes (CNTs) and other nanoscale particles in tissue and organs. Methods: In this research, we utilized a 3D model tissue of hepatocellular carcinoma (HCC)cultured in inverted colloidal crystal (ICC) scaffolds to compare the diffusivity of CNTs with small molecules such as Rhodamine and FITC in vitro, and further investigated the transportation of CNTs with and without targeting ligand, TGFβ1. The real-time permeation profiles of CNTs in HCC tissue model with high temporal and spatial resolution was demonstrated by using standard confocal microscopy. Quantitative analysis of the diffusion process inmore » 3D was carried out using luminescence intensity in a series of Z-stack images obtained for different time points of the diffusion process after initial addition of CNTs or small molecules to the cell culture and the image data was analyzed by software ImageJ and Mathematica. Results: CNTs display diffusion rate in model tissues substantially faster than small molecules of the similar charge such as FITC, and the diffusion rate of CNTs are significantly enhanced with targeting ligand, TGFβ1. Conclusion: In terms of the advantages of in-vitro model, we were able to have access to measuring the rate of CNT penetration at designed conditions with variable parameters. And the findings by using this model, changed our understanding about advantages of CNTs as nanoscale drug carriers and provides design principles for making new drug carriers for both treatment and diagnostics. Additionally the fast diffusion opens the discussion of the best possible drug carriers to reach deep parts of cancerous tissues, which is often a prerequisite for successful cancer treatment. This work was supported by the Center for Photonic and Multiscale Nanomaterials funded by National Science Foundation Materials Research Science and Engineering Center program DMR 1120923. The work was also partially supported by NSF grant ECS-0601345; EFRI-BSBA 0938019; CBET 0933384; CBET 0932823; CBET 1036672, AFOSR MURI 444286-P061716 and NIH 1R21CA121841-01A2.« less

The multinomial simulation algorithm for discrete stochastic simulation of reaction-diffusion systems.

PubMed

Lampoudi, Sotiria; Gillespie, Dan T; Petzold, Linda R

2009-03-07

The Inhomogeneous Stochastic Simulation Algorithm (ISSA) is a variant of the stochastic simulation algorithm in which the spatially inhomogeneous volume of the system is divided into homogeneous subvolumes, and the chemical reactions in those subvolumes are augmented by diffusive transfers of molecules between adjacent subvolumes. The ISSA can be prohibitively slow when the system is such that diffusive transfers occur much more frequently than chemical reactions. In this paper we present the Multinomial Simulation Algorithm (MSA), which is designed to, on the one hand, outperform the ISSA when diffusive transfer events outnumber reaction events, and on the other, to handle small reactant populations with greater accuracy than deterministic-stochastic hybrid algorithms. The MSA treats reactions in the usual ISSA fashion, but uses appropriately conditioned binomial random variables for representing the net numbers of molecules diffusing from any given subvolume to a neighbor within a prescribed distance. Simulation results illustrate the benefits of the algorithm.

Concentration profiles of actin-binding molecules in lamellipodia

NASA Astrophysics Data System (ADS)

Falcke, Martin

2016-04-01

Motile cells form lamellipodia in the direction of motion, which are flat membrane protrusions containing an actin filament network. The network flows rearward relative to the leading edge of the lamellipodium due to actin polymerization at the front. Thus, actin binding molecules are subject to transport towards the rear of the cell in the bound state and diffuse freely in the unbound state. We analyze this reaction-diffusion-advection process with respect to the concentration profiles of these species and provide an analytic approximation for them. Network flow may cause a depletion zone of actin binding molecules close to the leading edge. The existence of such zone depends on the free molecule concentration in the cell body, on the ratio of the diffusion length to the distance bound molecules travel rearward with the flow before dissociating, and the ratio of the diffusion length to the width of the region with network flow and actin binding. Our calculations suggest the existence of depletion zones for the F-actin cross-linkers filamin and α-actinin in fish keratocytes (and other cell types), which is in line with the small elastic moduli of the F-actin network close to the leading edge found in measurements of the force motile cells are able to exert.

Analysis of Molecular Movement Reveals Latticelike Obstructions to Diffusion in Heart Muscle Cells

PubMed Central

Illaste, Ardo; Laasmaa, Martin; Peterson, Pearu; Vendelin, Marko

2012-01-01

Intracellular diffusion in muscle cells is known to be restricted. Although characteristics and localization of these restrictions is yet to be elucidated, it has been established that ischemia-reperfusion injury reduces the overall diffusion restriction. Here we apply an extended version of raster image correlation spectroscopy to determine directional anisotropy and coefficients of diffusion in rat cardiomyocytes. Our experimental results indicate that diffusion of a smaller molecule (1127 MW fluorescently labeled ATTO633-ATP) is restricted more than that of a larger one (10,000 MW Alexa647-dextran), when comparing diffusion in cardiomyocytes to that in solution. We attempt to provide a resolution to this counterintuitive result by applying a quantitative stochastic model of diffusion. Modeling results suggest the presence of periodic intracellular barriers situated ∼1 μm apart having very low permeabilities and a small effect of molecular crowding in volumes between the barriers. Such intracellular structuring could restrict diffusion of molecules of energy metabolism, reactive oxygen species, and apoptotic signals, enacting a significant role in normally functioning cardiomyocytes as well as in pathological conditions of the heart. PMID:22385844

The bubble method of water purification

NASA Astrophysics Data System (ADS)

Smirnov, B. M.; Babaeva, N. Yu.; Naidis, G. V.; Panov, V. A.; Saveliev, A. S.; Son, E. E.; Tereshonok, D. V.

2018-02-01

The processes of water purification from admixture molecules are analyzed. The purification rate is limited due to a low diffusion coefficient of the admixture molecules in water. At non-small concentrations of the admixture molecules, the water purication can proceed through association of molecules in condensed nanoparticles which fall on the bottom of the water volume. The rate of association may be increased in an external electric field, but in reality this cannot change significantly the rate of the purification process. The bubble method of water purification is considered, where air bubbles formed at the bottom of the water volume, transfer admixture molecules to the interface. This method allows one to clean small water volumes fast. This mechanism of water purification is realized experimentally and exhibits the promises of the bubble purification method.

Resolving Fast, Confined Diffusion in Bacteria with Image Correlation Spectroscopy.

PubMed

Rowland, David J; Tuson, Hannah H; Biteen, Julie S

2016-05-24

By following single fluorescent molecules in a microscope, single-particle tracking (SPT) can measure diffusion and binding on the nanometer and millisecond scales. Still, although SPT can at its limits characterize the fastest biomolecules as they interact with subcellular environments, this measurement may require advanced illumination techniques such as stroboscopic illumination. Here, we address the challenge of measuring fast subcellular motion by instead analyzing single-molecule data with spatiotemporal image correlation spectroscopy (STICS) with a focus on measurements of confined motion. Our SPT and STICS analysis of simulations of the fast diffusion of confined molecules shows that image blur affects both STICS and SPT, and we find biased diffusion rate measurements for STICS analysis in the limits of fast diffusion and tight confinement due to fitting STICS correlation functions to a Gaussian approximation. However, we determine that with STICS, it is possible to correctly interpret the motion that blurs single-molecule images without advanced illumination techniques or fast cameras. In particular, we present a method to overcome the bias due to image blur by properly estimating the width of the correlation function by directly calculating the correlation function variance instead of using the typical Gaussian fitting procedure. Our simulation results are validated by applying the STICS method to experimental measurements of fast, confined motion: we measure the diffusion of cytosolic mMaple3 in living Escherichia coli cells at 25 frames/s under continuous illumination to illustrate the utility of STICS in an experimental parameter regime for which in-frame motion prevents SPT and tight confinement of fast diffusion precludes stroboscopic illumination. Overall, our application of STICS to freely diffusing cytosolic protein in small cells extends the utility of single-molecule experiments to the regime of fast confined diffusion without requiring advanced microscopy techniques. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Phenomenology and energetics of diffusion across cell phase states.

PubMed

Ashrafuzzaman, Md

2015-11-01

Cell based transport properties have been mathematically addressed. Cell contained cross boundary diffusion of materials has been explained using valid formalisms and related analytical expressions have been developed. Various distinguishable physical structures and their properties raise different general structure specific diffusion mechanisms and controlled transport related parameters. Some of these parameters play phenomenological roles and some cause regulatory effects. The cell based compartments may be divided into three major physical phase states namely liquid, plasma and solid phase states. Transport of ions, nutrients, small molecules like proteins, etc. across inter phase states and intraphase states follows general transport related formalisms. Creation of some localized permanent and/or temporary structures e.g., ion channels, clustering of constituents, etc. and the transitions between such structures appear as regulators of the transport mechanisms. In this article, I have developed mainly a theoretical analysis of the commonly observed cell transport phenomena. I have attempted to develop formalisms on general cell based diffusion followed by a few numerical computations to address the analytical expression phenomenologically. I have then extended the analysis to adopting with the local structure originated energetics. Independent or correlated molecular transport naturally relies on some general parameters that define the nature of local cell environment as well as on some occasionally raised or transiently active stochastic resonance due to localized interactions. Short and long range interaction energies play crucial roles in this regard. Physical classification of cellular compartments has led us developing analytical expressions on both biologically observed diffusion mechanisms and the diffusions's occasional stochasticity causing energetics. These analytical expressions help us address the diffusion phenomena generally considering the physical properties of the biostructures across the diffusion pathways. A specific example case of single molecule transport and localized interaction energetics in a specific cell phase has been utilized to address the diffusion quite clearly. This article helps to address the mechanisms of cell based diffusion and nutrient movements and thus helps develop strategic templates to manipulate the diffusion mechanisms. Application of the theoretical knowledge into designing or discovering drugs or small molecule inhibitors targeting cell based structures may open up new avenues in biomedical sciences.

Electrostatic coupling between DNA and its counterions modulates the observed translational diffusion coefficients.

PubMed

Stellwagen, Earle; Stellwagen, Nancy C

2015-09-01

Free solution capillary electrophoresis (CE) is a useful technique for measuring the translational diffusion coefficients of charged analytes. The measurements are relatively fast if the polarity of the electric field is reversed to drive the analyte back and forth past the detection window during each run. We have tested the validity of the resulting diffusion coefficients using double-stranded DNA molecules ranging in size from 20 to 960 base pairs as the model system. The diffusion coefficients of small DNAs are equal to values in the literature measured by other techniques. However, the diffusion coefficients of DNA molecules larger than ∼30 base pairs are anomalously high and deviate increasingly from the literature values with increasing DNA molar mass. The anomalously high diffusion coefficients are due to electrostatic coupling between the DNA and its counterions. As a result, the measured diffusion coefficients vary with the diffusion coefficient of the counterion, as well as with cation concentration and electric field strength. These effects can be reduced or eliminated by measuring apparent diffusion coefficients of the DNA at several different electric field strengths and extrapolating the results to zero electric field.

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

Sarman, Sten, E-mail: sarman@ownit.nu; Wang, Yong-Lei; Laaksonen, Aatto

The self-diffusion coefficients of nematic phases of various model systems consisting of regular convex calamitic and discotic ellipsoids and non-convex bodies such as bent-core molecules and soft ellipsoid strings have been obtained as functions of the shear rate in a shear flow. Then the self-diffusion coefficient is a second rank tensor with three different diagonal components and two off-diagonal components. These coefficients were found to be determined by a combination of two mechanisms, which previously have been found to govern the self-diffusion of shearing isotropic liquids, namely, (i) shear alignment enhancing the diffusion in the direction parallel to the streamlinesmore » and hindering the diffusion in the perpendicular directions and (ii) the distortion of the shell structure in the liquid whereby a molecule more readily can escape from a surrounding shell of nearest neighbors, so that the mobility increases in every direction. Thus, the diffusion parallel to the streamlines always increases with the shear rate since these mechanisms cooperate in this direction. In the perpendicular directions, these mechanisms counteract each other so that the behaviour becomes less regular. In the case of the nematic phases of the calamitic and discotic ellipsoids and of the bent core molecules, mechanism (ii) prevails so that the diffusion coefficients increase. However, the diffusion coefficients of the soft ellipsoid strings decrease in the direction of the velocity gradient because the broadsides of these molecules are oriented perpendicularly to this direction due the shear alignment (i). The cross coupling coefficient relating a gradient of tracer particles in the direction of the velocity gradient and their flow in the direction of the streamlines is negative and rather large, whereas the other coupling coefficient relating a gradient in the direction of the streamlines and a flow in the direction of the velocity gradient is very small.« less

Diffusion of molecules and macromolecules in thylakoid membranes.

PubMed

Kirchhoff, Helmut

2014-04-01

The survival and fitness of photosynthetic organisms is critically dependent on the flexible response of the photosynthetic machinery, harbored in thylakoid membranes, to environmental changes. A central element of this flexibility is the lateral diffusion of membrane components along the membrane plane. As demonstrated, almost all functions of photosynthetic energy conversion are dependent on lateral diffusion. The mobility of both small molecules (plastoquinone, xanthophylls) as well as large protein supercomplexes is very sensitive to changes in structural boundary conditions. Knowledge about the design principles that govern the mobility of photosynthetic membrane components is essential to understand the dynamic response of the photosynthetic machinery. This review summarizes our knowledge about the factors that control diffusion in thylakoid membranes and bridges structural membrane alterations to changes in mobility and function. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulation Mechanism of the Lateral Diffusion of Band 3 in Erythrocyte Membranes by the Membrane Skeleton

PubMed Central

Tomishige, Michio; Sako, Yasushi; Kusumi, Akihiro

1998-01-01

Mechanisms that regulate the movement of a membrane spanning protein band 3 in erythrocyte ghosts were investigated at the level of a single or small groups of molecules using single particle tracking with an enhanced time resolution (0.22 ms). Two-thirds of band 3 undergo macroscopic diffusion: a band 3 molecule is temporarily corralled in a mesh of 110 nm in diameter, and hops to an adjacent mesh an average of every 350 ms. The rest (one-third) of band 3 exhibited oscillatory motion similar to that of spectrin, suggesting that these band 3 molecules are bound to spectrin. When the membrane skeletal network was dragged and deformed/translated using optical tweezers, band 3 molecules that were undergoing hop diffusion were displaced toward the same direction as the skeleton. Mild trypsin treatment of ghosts, which cleaves off the cytoplasmic portion of band 3 without affecting spectrin, actin, and protein 4.1, increased the intercompartmental hop rate of band 3 by a factor of 6, whereas it did not change the corral size and the microscopic diffusion rate within a corral. These results indicate that the cytoplasmic portion of band 3 collides with the membrane skeleton, which causes temporal confinement of band 3 inside a mesh of the membrane skeleton. PMID:9722611

Exporters for Production of Amino Acids and Other Small Molecules.

PubMed

Eggeling, Lothar

Microbes are talented catalysts to synthesize valuable small molecules in their cytosol. However, to make full use of their skills - and that of metabolic engineers - the export of intracellularly synthesized molecules to the culture medium has to be considered. This step is as essential as is each step for the synthesis of the favorite molecule of the metabolic engineer, but is frequently not taken into account. To export small molecules via the microbial cell envelope, a range of different types of carrier proteins is recognized to be involved, which are primary active carriers, secondary active carriers, or proteins increasing diffusion. Relevant export may require just one carrier as is the case with L-lysine export by Corynebacterium glutamicum or involve up to four carriers as known for L-cysteine excretion by Escherichia coli. Meanwhile carriers for a number of small molecules of biotechnological interest are recognized, like for production of peptides, nucleosides, diamines, organic acids, or biofuels. In addition to carriers involved in amino acid excretion, such carriers and their impact on product formation are described, as well as the relatedness of export carriers which may serve as a hint to identify further carriers required to improve product formation by engineering export.

Quantum angular momentum diffusion of rigid bodies

NASA Astrophysics Data System (ADS)

Papendell, Birthe; Stickler, Benjamin A.; Hornberger, Klaus

2017-12-01

We show how to describe the diffusion of the quantized angular momentum vector of an arbitrarily shaped rigid rotor as induced by its collisional interaction with an environment. We present the general form of the Lindblad-type master equation and relate it to the orientational decoherence of an asymmetric nanoparticle in the limit of small anisotropies. The corresponding diffusion coefficients are derived for gas particles scattering off large molecules and for ambient photons scattering off dielectric particles, using the elastic scattering amplitudes.

Fast Rotational Diffusion of Water Molecules in a 2D Hydrogen Bond Network at Cryogenic Temperatures

NASA Astrophysics Data System (ADS)

Prisk, T. R.; Hoffmann, C.; Kolesnikov, A. I.; Mamontov, E.; Podlesnyak, A. A.; Wang, X.; Kent, P. R. C.; Anovitz, L. M.

2018-05-01

Individual water molecules or small clusters of water molecules contained within microporous minerals present an extreme case of confinement where the local structure of hydrogen bond networks are dramatically altered from bulk water. In the zinc silicate hemimorphite, the water molecules form a two-dimensional hydrogen bond network with hydroxyl groups in the crystal framework. Here, we present a combined experimental and theoretical study of the structure and dynamics of water molecules within this network. The water molecules undergo a continuous phase transition in their orientational configuration analogous to a two-dimensional Ising model. The incoherent dynamic structure factor reveals two thermally activated relaxation processes, one on a subpicosecond timescale and another on a 10-100 ps timescale, between 70 and 130 K. The slow process is an in-plane reorientation of the water molecule involving the breaking of hydrogen bonds with a framework that, despite the low temperatures involved, is analogous to rotational diffusion of water molecules in the bulk liquid. The fast process is a localized motion of the water molecule with no apparent analogs among known bulk or confined phases of water.

Fast Rotational Diffusion of Water Molecules in a 2D Hydrogen Bond Network at Cryogenic Temperatures

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

Prisk, Timothy; Hoffmann, Christina; Kolesnikov, Alexander I.

Individual water molecules or small clusters of water molecules contained within microporous minerals present an extreme case of confinement where the local structure of hydrogen bond networks are dramatically altered from bulk water. In the zinc silicate hemimorphite, the water molecules form a two-dimensional hydrogen bond network with hydroxyl groups in the crystal framework. Here in this paper, we present a combined experimental and theoretical study of the structure and dynamics of water molecules within this network. The water molecules undergo a continuous phase transition in their orientational configuration analogous to a two-dimensional Ising model. The incoherent dynamic structure factormore » reveals two thermally activated relaxation processes, one on a subpicosecond timescale and another on a 10–100 ps timescale, between 70 and 130 K. The slow process is an in-plane reorientation of the water molecule involving the breaking of hydrogen bonds with a framework that, despite the low temperatures involved, is analogous to rotational diffusion of water molecules in the bulk liquid. The fast process is a localized motion of the water molecule with no apparent analogs among known bulk or confined phases of water.« less

Fast Rotational Diffusion of Water Molecules in a 2D Hydrogen Bond Network at Cryogenic Temperatures

DOE PAGES

Prisk, Timothy; Hoffmann, Christina; Kolesnikov, Alexander I.; ...

2018-05-09

Individual water molecules or small clusters of water molecules contained within microporous minerals present an extreme case of confinement where the local structure of hydrogen bond networks are dramatically altered from bulk water. In the zinc silicate hemimorphite, the water molecules form a two-dimensional hydrogen bond network with hydroxyl groups in the crystal framework. Here in this paper, we present a combined experimental and theoretical study of the structure and dynamics of water molecules within this network. The water molecules undergo a continuous phase transition in their orientational configuration analogous to a two-dimensional Ising model. The incoherent dynamic structure factormore » reveals two thermally activated relaxation processes, one on a subpicosecond timescale and another on a 10–100 ps timescale, between 70 and 130 K. The slow process is an in-plane reorientation of the water molecule involving the breaking of hydrogen bonds with a framework that, despite the low temperatures involved, is analogous to rotational diffusion of water molecules in the bulk liquid. The fast process is a localized motion of the water molecule with no apparent analogs among known bulk or confined phases of water.« less

Using light transmission to watch hydrogen diffuse

PubMed Central

Pálsson, Gunnar K.; Bliersbach, Andreas; Wolff, Max; Zamani, Atieh; Hjörvarsson, Björgvin

2012-01-01

Because of its light weight and small size, hydrogen exhibits one of the fastest diffusion rates in solid materials, comparable to the diffusion rate of liquid water molecules at room temperature. The diffusion rate is determined by an intricate combination of quantum effects and dynamic interplay with the displacement of host atoms that is still only partially understood. Here we present direct observations of the spatial and temporal changes in the diffusion-induced concentration profiles in a vanadium single crystal and we show that the results represent the experimental counterpart of the full time and spatial solution of Fick's diffusion equation. We validate the approach by determining the diffusion rate of hydrogen in a single crystal vanadium (001) film, with net diffusion in the [110] direction. PMID:22692535

Using light transmission to watch hydrogen diffuse

NASA Astrophysics Data System (ADS)

Pálsson, Gunnar K.; Bliersbach, Andreas; Wolff, Max; Zamani, Atieh; Hjörvarsson, Björgvin

2012-06-01

Because of its light weight and small size, hydrogen exhibits one of the fastest diffusion rates in solid materials, comparable to the diffusion rate of liquid water molecules at room temperature. The diffusion rate is determined by an intricate combination of quantum effects and dynamic interplay with the displacement of host atoms that is still only partially understood. Here we present direct observations of the spatial and temporal changes in the diffusion-induced concentration profiles in a vanadium single crystal and we show that the results represent the experimental counterpart of the full time and spatial solution of Fick's diffusion equation. We validate the approach by determining the diffusion rate of hydrogen in a single crystal vanadium (001) film, with net diffusion in the [110] direction.

Analysis of molecular movement reveals latticelike obstructions to diffusion in heart muscle cells.

PubMed

Illaste, Ardo; Laasmaa, Martin; Peterson, Pearu; Vendelin, Marko

2012-02-22

Intracellular diffusion in muscle cells is known to be restricted. Although characteristics and localization of these restrictions is yet to be elucidated, it has been established that ischemia-reperfusion injury reduces the overall diffusion restriction. Here we apply an extended version of raster image correlation spectroscopy to determine directional anisotropy and coefficients of diffusion in rat cardiomyocytes. Our experimental results indicate that diffusion of a smaller molecule (1127 MW fluorescently labeled ATTO633-ATP) is restricted more than that of a larger one (10,000 MW Alexa647-dextran), when comparing diffusion in cardiomyocytes to that in solution. We attempt to provide a resolution to this counterintuitive result by applying a quantitative stochastic model of diffusion. Modeling results suggest the presence of periodic intracellular barriers situated ∼1 μm apart having very low permeabilities and a small effect of molecular crowding in volumes between the barriers. Such intracellular structuring could restrict diffusion of molecules of energy metabolism, reactive oxygen species, and apoptotic signals, enacting a significant role in normally functioning cardiomyocytes as well as in pathological conditions of the heart. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

How does the isomerization rate affect the photoisomerization-induced transport properties of a doped molecular glass-former?

NASA Astrophysics Data System (ADS)

Accary, J.-B.; Teboul, V.

2013-07-01

We investigate the effect of the isomerization rate f on the microscopic mechanisms at the origin of the massive mass transport found in glass-formers doped with isomerizing azobenzene molecules that result in surface relief gratings formation. To this end we simulate the isomerization of dispersed probe molecules embedded into a molecular host glass-former. The host diffusion coefficient first increases linearly with f and then saturates. The saturated value of the diffusion coefficient and of the viscosity does not depend on f but increases with temperature while the linear response for these transport coefficients depends only slightly on the temperature. We interpret this saturation as arising from the appearance of increasingly soft regions around the probes for high isomerization rates, a result in qualitative agreement with experiments. These two different physical behaviors, linear response and saturation, are reminiscent of the two different unexplained mass transport mechanisms observed for small or large light intensities (for small intensities the molecules move towards the dark regions while for large intensities they move towards the illuminated regions).

Nanoscale structure, dynamics and power conversion efficiency correlations in small molecule and oligomer-based photovoltaic devices

PubMed Central

Szarko, Jodi M.; Guo, Jianchang; Rolczynski, Brian S.; Chen, Lin X.

2011-01-01

Photovoltaic functions in organic materials are intimately connected to interfacial morphologies of molecular packing in films on the nanometer scale and molecular levels. This review will focus on current studies on correlations of nanoscale morphologies in organic photovoltaic (OPV) materials with fundamental processes relevant to photovoltaic functions, such as light harvesting, exciton splitting, exciton diffusion, and charge separation (CS) and diffusion. Small molecule photovoltaic materials will be discussed here. The donor and acceptor materials in small molecule OPV devices can be fabricated in vacuum-deposited, multilayer, crystalline thin films, or spin-coated together to form blended bulk heterojunction (BHJ) films. These two methods result in very different morphologies of the solar cell active layers. There is still a formidable debate regarding which morphology is favored for OPV optimization. The morphology of the conducting films has been systematically altered; using variations of the techniques above, the whole spectrum of film qualities can be fabricated. It is possible to form a highly crystalline material, one which is completely amorphous, or an intermediate morphology. In this review, we will summarize the past key findings that have driven organic solar cell research and the current state-of-the-art of small molecule and conducting oligomer materials. We will also discuss the merits and drawbacks of these devices. Finally, we will highlight some works that directly compare the spectra and morphology of systematically elongated oligothiophene derivatives and compare these oligomers to their polymer counterparts. We hope this review will shed some new light on the morphology differences of these two systems. PMID:22110870

Development and application of an exchange model for anisotropic water diffusion in the microporous MOF aluminum fumarate

NASA Astrophysics Data System (ADS)

Splith, Tobias; Fröhlich, Dominik; Henninger, Stefan K.; Stallmach, Frank

2018-06-01

Diffusion of water in aluminum fumarate was studied by means of pulsed field gradient (PFG) nuclear magnetic resonance (NMR). Due to water molecules exchanging between the intracrystalline anisotropic pore space and the isotropic intercrystalline void space the model of intracrystalline anisotropic diffusion fails to describe the experimental PFG NMR data at high observation times. Therefore, the two-site exchange model developed by Kärger is extended to the case of exchange between an anisotropic and an isotropic site. This extended exchange model is solved by numerical integration. It describes the experimental data very well and yields values for the intracrystalline diffusion coefficient and the mean residence times of the respective sites. Further PFG NMR studies were performed with coatings consisting of small aluminum fumarate crystals, which are used in adsorptive heat transformation applications. The diffusion coefficients of water in the small crystal coating are compared to the values expected from the extended two-site exchange model and from the model of long-range diffusion.

Self-diffusion in the non-Newtonian regime of shearing liquid crystal model systems based on the Gay-Berne potential

NASA Astrophysics Data System (ADS)

Sarman, Sten; Wang, Yong-Lei; Laaksonen, Aatto

2016-02-01

The self-diffusion coefficients of nematic phases of various model systems consisting of regular convex calamitic and discotic ellipsoids and non-convex bodies such as bent-core molecules and soft ellipsoid strings have been obtained as functions of the shear rate in a shear flow. Then the self-diffusion coefficient is a second rank tensor with three different diagonal components and two off-diagonal components. These coefficients were found to be determined by a combination of two mechanisms, which previously have been found to govern the self-diffusion of shearing isotropic liquids, namely, (i) shear alignment enhancing the diffusion in the direction parallel to the streamlines and hindering the diffusion in the perpendicular directions and (ii) the distortion of the shell structure in the liquid whereby a molecule more readily can escape from a surrounding shell of nearest neighbors, so that the mobility increases in every direction. Thus, the diffusion parallel to the streamlines always increases with the shear rate since these mechanisms cooperate in this direction. In the perpendicular directions, these mechanisms counteract each other so that the behaviour becomes less regular. In the case of the nematic phases of the calamitic and discotic ellipsoids and of the bent core molecules, mechanism (ii) prevails so that the diffusion coefficients increase. However, the diffusion coefficients of the soft ellipsoid strings decrease in the direction of the velocity gradient because the broadsides of these molecules are oriented perpendicularly to this direction due the shear alignment (i). The cross coupling coefficient relating a gradient of tracer particles in the direction of the velocity gradient and their flow in the direction of the streamlines is negative and rather large, whereas the other coupling coefficient relating a gradient in the direction of the streamlines and a flow in the direction of the velocity gradient is very small.

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PubMed

Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

2015-04-01

Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

Formation of blade and slot die coated small molecule multilayers for OLED applications studied theoretically and by XPS depth profiling

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

Peters, Katharina; Raupp, Sebastian, E-mail: sebastian.raupp@kit.edu; Scharfer, Philip

2016-06-15

Slot die coaters especially designed for low material consumption and doctor blades were used to process small molecule solutions for organic light-emitting diodes (OLEDs). Optimum process parameters were developed for the large-scale coating techniques to generate stable single and multiple layers only a few nanometers thick. Achieving a multilayer architecture for solution-processed OLEDs is the most challenging step. X-ray photoelectron spectroscopy sputter depth profiling was performed to determine defined interfaces between coated organic layers. Commercially available small molecules NPB (N,N’-Di(1-naphthyl)-N,N’-diphenyl-(1,1’-biphenyl)-4,4’-diamine) and BAlq (Bis(8-hdroxy-2methylquinoline)-(4-phenylphenoxy)aluminum), originally developed for vacuum deposition, were used as hole, respectively electron transport material. Defined double-layers were processedmore » with both scalable coating methods using the orthogonal solvent approach. The use of non-orthogonal solvents resulted in complete intermixing of the material. The results are explained by calculations of solubilities and simulating drying and diffusion kinetics of the small molecule solutions.« less

Formation of blade and slot die coated small molecule multilayers for OLED applications studied theoretically and by XPS depth profiling

NASA Astrophysics Data System (ADS)

Peters, Katharina; Raupp, Sebastian; Hummel, Helga; Bruns, Michael; Scharfer, Philip; Schabel, Wilhelm

2016-06-01

Slot die coaters especially designed for low material consumption and doctor blades were used to process small molecule solutions for organic light-emitting diodes (OLEDs). Optimum process parameters were developed for the large-scale coating techniques to generate stable single and multiple layers only a few nanometers thick. Achieving a multilayer architecture for solution-processed OLEDs is the most challenging step. X-ray photoelectron spectroscopy sputter depth profiling was performed to determine defined interfaces between coated organic layers. Commercially available small molecules NPB (N,N'-Di(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine) and BAlq (Bis(8-hdroxy-2methylquinoline)-(4-phenylphenoxy)aluminum), originally developed for vacuum deposition, were used as hole, respectively electron transport material. Defined double-layers were processed with both scalable coating methods using the orthogonal solvent approach. The use of non-orthogonal solvents resulted in complete intermixing of the material. The results are explained by calculations of solubilities and simulating drying and diffusion kinetics of the small molecule solutions.

Drug transport across the blood–brain barrier

PubMed Central

Pardridge, William M

2012-01-01

The blood–brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. This property arises from the epithelial-like tight junctions within the brain capillary endothelium. The BBB is anatomically and functionally distinct from the blood–cerebrospinal fluid barrier at the choroid plexus. Certain small molecule drugs may cross the BBB via lipid-mediated free diffusion, providing the drug has a molecular weight <400 Da and forms <8 hydrogen bonds. These chemical properties are lacking in the majority of small molecule drugs, and all large molecule drugs. Nevertheless, drugs can be reengineered for BBB transport, based on the knowledge of the endogenous transport systems within the BBB. Small molecule drugs can be synthesized that access carrier-mediated transport (CMT) systems within the BBB. Large molecule drugs can be reengineered with molecular Trojan horse delivery systems to access receptor-mediated transport (RMT) systems within the BBB. Peptide and antisense radiopharmaceuticals are made brain-penetrating with the combined use of RMT-based delivery systems and avidin–biotin technology. Knowledge on the endogenous CMT and RMT systems expressed at the BBB enable new solutions to the problem of BBB drug transport. PMID:22929442

Effect of temperature and pressure on the dynamics of nanoconfined propane

NASA Astrophysics Data System (ADS)

Gautam, Siddharth; Liu, Tingting; Rother, Gernot; Jalarvo, Niina; Mamontov, Eugene; Welch, Susan; Cole, David

2014-04-01

We report the effect of temperature and pressure on the dynamical properties of propane confined in nanoporous silica aerogel studied using quasielastic neutron scattering (QENS). Our results demonstrate that the effect of a change in the pressure dominates over the effect of temperature variation on the dynamics of propane nano-confined in silica aerogel. At low pressures, most of the propane molecules are strongly bound to the pore walls, only a small fraction is mobile. As the pressure is increased, the fraction of mobile molecules increases. A change in the mechanism of motion, from continuous diffusion at low pressures to jump diffusion at higher pressures has also been observed.

Simulations of singlet exciton diffusion in organic semiconductors: a review

DOE PAGES

Bjorgaard, Josiah A.; Kose, Muhammet Erkan

2014-12-22

Our review describes the various aspects of simulation strategies for exciton diffusion in condensed phase thin films of organic semiconductors. Several methods for calculating energy transfer rate constants are discussed along with procedures for how to account for energetic disorder. Exciton diffusion can be modelled by using kinetic Monte-Carlo methods or master equations. Recent literature on simulation efforts for estimating exciton diffusion lengths of various conjugated polymers and small molecules are introduced. Moreover, these studies are discussed in the context of the effects of morphology on exciton diffusion and the necessity of accurate treatment of disorder for comparison of simulationmore » results with those of experiment.« less

Apparent Activation Energies Associated with Protein Dynamics on Hydrophobic and Hydrophilic Surfaces

PubMed Central

Langdon, Blake B.; Kastantin, Mark; Schwartz, Daniel K.

2012-01-01

With the use of single-molecule total internal reflection fluorescence microscopy (TIRFM), the dynamics of bovine serum albumin (BSA) and human fibrinogen (Fg) at low concentrations were observed at the solid-aqueous interface as a function of temperature on hydrophobic trimethylsilane (TMS) and hydrophilic fused silica (FS) surfaces. Multiple dynamic modes and populations were observed and characterized by their surface residence times and squared-displacement distributions (surface diffusion). Characteristic desorption and diffusion rates for each population/mode were generally found to increase with temperature, and apparent activation energies were determined from Arrhenius analyses. The apparent activation energies of desorption and diffusion were typically higher on FS than on TMS surfaces, suggesting that protein desorption and mobility were hindered on hydrophilic surfaces due to favorable protein-surface and solvent-surface interactions. The diffusion of BSA on TMS appeared to be activationless for several populations, whereas diffusion on FS always exhibited an apparent activation energy. All activation energies were small in absolute terms (generally only a few kBT), suggesting that most adsorbed protein molecules are weakly bound and move and desorb readily under ambient conditions. PMID:22713578

Multiscale Spectroscopy of Diffusing Molecules in Crowded Environments

NASA Astrophysics Data System (ADS)

Heikal, Ahmed A.

2015-06-01

Living cells are known to be crowded with organelles, biomembranes, and macromolecules such as proteins, DNA, RNA, and actin filaments. It is believed that such macromolecular crowding affect biomolecular diffusion, protein-protein and protein-substrate interaction, and protein folding. In this contribution, I will discuss our recent results on rotational and translational diffusion of small and large molecules in crowded environments using time-resolved anisotropy and fluorescence correlation spectroscopy methods. In these studies, rhodamine green and enhanced green fluorescent protein are used as fluorescent probes diffusing in buffers enriched with biomimetic crowding agents such as Ficoll-70, bovine serum albumin (BSA), and ovalbumin. Controlled experiments on pure and glycerol-rich buffers were carried out as environments with variable, homogeneous viscosity. Our results indicate that the microviscosity differs from the corresponding bulk viscosity, depending on the nature of crowding agents (i.e., proteins versus polymers), the concentration of crowding agents and spatio-temporal scaling of our experimental approach. Our findings provide a foundation for fluorescence-based studies of diffusion and binding of biomolecules in the crowded milieu of living cells.

Manipulating and Visualizing Molecular Interactions in Customized Nanoscale Spaces

NASA Astrophysics Data System (ADS)

Stabile, Francis; Henkin, Gil; Berard, Daniel; Shayegan, Marjan; Leith, Jason; Leslie, Sabrina

We present a dynamically adjustable nanofluidic platform for formatting the conformations of and visualizing the interaction kinetics between biomolecules in solution, offering new time resolution and control of the reaction processes. This platform extends convex lens-induced confinement (CLiC), a technique for imaging molecules under confinement, by introducing a system for in situ modification of the chemical environment; this system uses a deep microchannel to diffusively exchange reagents within the nanoscale imaging region, whose height is fixed by a nanopost array. To illustrate, we visualize and manipulate salt-induced, surfactant-induced, and enzyme-induced reactions between small-molecule reagents and DNA molecules, where the conformations of the DNA molecules are formatted by the imposed nanoscale confinement. By using nanofabricated, nonabsorbing, low-background glass walls to confine biomolecules, our nanofluidic platform facilitates quantitative exploration of physiologically and biotechnologically relevant processes at the nanoscale. This device provides new kinetic information about dynamic chemical processes at the single-molecule level, using advancements in the CLiC design including a microchannel-based diffuser and postarray-based dialysis slit.

The Diffusion Process in Small Particles and Brownian Motion

NASA Astrophysics Data System (ADS)

Khoshnevisan, M.

Albert Einstein in 1926 published his book entitled ''INVESTIGATIONS ON THE THEORY OF THE BROWNIAN MOVEMENT''. He investigated the process of diffusion in an undissociated dilute solution. The diffusion process is subject to Brownian motion. Furthermore, he elucidated the fact that the heat content of a substance will change the position of the single molecules in an irregular fashion. In this paper, I have shown that in order for the displacement of the single molecules to be proportional to the square root of the time, and for v/2 - v 1 Δ =dv/dx , (where v1 and v2 are the concentrations in two cross sections that are separated by a very small distance), ∫ - ∞ ∞ Φ (Δ) dΔ = I and I/τ ∫ - ∞ ∞Δ2/2 Φ (Δ) dΔ = D conditions to hold, then equation (7a) D =√{ 2 D }√{ τ} must be changed to Δ =√{ 2 D }√{ τ} . I have concluded that D =√{ 2 D }√{ τ} is an unintended error, and it has not been amended for almost 90 years in INVESTIGATIONS ON THE THEORY OF THE BROWNIAN MOVEMENT, 1926 publication.

Mechanobiological induction of long-range contractility by diffusing biomolecules and size scaling in cell assemblies

NASA Astrophysics Data System (ADS)

Dasbiswas, K.; Alster, E.; Safran, S. A.

2016-06-01

Mechanobiological studies of cell assemblies have generally focused on cells that are, in principle, identical. Here we predict theoretically the effect on cells in culture of locally introduced biochemical signals that diffuse and locally induce cytoskeletal contractility which is initially small. In steady-state, both the concentration profile of the signaling molecule as well as the contractility profile of the cell assembly are inhomogeneous, with a characteristic length that can be of the order of the system size. The long-range nature of this state originates in the elastic interactions of contractile cells (similar to long-range “macroscopic modes” in non-living elastic inclusions) and the non-linear diffusion of the signaling molecules, here termed mechanogens. We suggest model experiments on cell assemblies on substrates that can test the theory as a prelude to its applicability in embryo development where spatial gradients of morphogens initiate cellular development.

Kinetics of proton migration in liquid water.

PubMed

Chen, Hanning; Voth, Gregory A; Agmon, Noam

2010-01-14

We have utilized multistate empirical valence bond (MS-EVB3) simulations of protonated liquid water to calculate the relative mean-square displacement (MSD) and the history-independent time correlation function, c(t), of the hydrated proton center of excess charge (CEC) with respect to the water molecule on which it has initially resided. The MSD is nonlinear for the first 15 ps, suggesting that the relative diffusion coefficient increases from a small value, D(0), at short separations to its larger bulk value, D(infinity), at large separations. With the ensuing distance-dependent diffusion coefficient, D(r), the time dependence of both the MSD and c(t) agrees quantitatively with the solution of a diffusion equation for reversible geminate recombination. This suggests that the relative motion of the CEC is not independent from the nearby water molecules, in agreement with theoretical and experimental observations that large water clusters participate in the mechanism of proton mobility.

Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

PubMed

Palmgren, Madelene; Hernebring, Malin; Eriksson, Stefanie; Elbing, Karin; Geijer, Cecilia; Lasič, Samo; Dahl, Peter; Hansen, Jesper S; Topgaard, Daniel; Lindkvist-Petersson, Karin

2017-12-01

Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

Improving the prospects of cleavage-based nanopore sequencing engines

NASA Astrophysics Data System (ADS)

Brady, Kyle T.; Reiner, Joseph E.

2015-08-01

Recently proposed methods for DNA sequencing involve the use of cleavage-based enzymes attached to the opening of a nanopore. The idea is that DNA interacting with either an exonuclease or polymerase protein will lead to a small molecule being cleaved near the mouth of the nanopore, and subsequent entry into the pore will yield information about the DNA sequence. The prospects for this approach seem promising, but it has been shown that diffusion related effects impose a limit on the capture probability of molecules by the pore, which limits the efficacy of the technique. Here, we revisit the problem with the goal of optimizing the capture probability via a step decrease in the nucleotide diffusion coefficient between the pore and bulk solutions. It is shown through random walk simulations and a simplified analytical model that decreasing the molecule's diffusion coefficient in the bulk relative to its value in the pore increases the nucleotide capture probability. Specifically, we show that at sufficiently high applied transmembrane potentials (≥100 mV), increasing the potential by a factor f is equivalent to decreasing the diffusion coefficient ratio Dbulk/Dpore by the same factor f. This suggests a promising route toward implementation of cleavage-based sequencing protocols. We also discuss the feasibility of forming a step function in the diffusion coefficient across the pore-bulk interface.

A new fluorogenic small molecule labeling tool for surface diffusion analysis and advanced fluorescence imaging of β-site amyloid precursor protein (APP)-cleaving enzyme 1 based on silicone rhodamine: SiR-BACE1.

PubMed

Karch, Sandra; Broichhagen, Johannes; Schneider, Julia; Böning, Daniel; Hartmann, Stephanie; Schmid, Benjamin; Tripal, Philipp; Palmisano, Ralf; Alzheimer, Christian; Johnsson, Kai; Huth, Tobias

2018-06-25

β-site APP-cleaving enzyme 1 (BACE1) is a major player in the pathogenesis of Alzheimer's disease. Structural and functional fluorescence microscopy offers a powerful approach to learn about the physiology and pathophysiology of this protease. Up to now, however, common labeling techniques either require genetic manipulation, use large antibodies, or are not compatible with live cell imaging. Fluorescent small molecules that specifically bind to the protein of interest can overcome these limitations. Herein, we introduce SiR-BACE1, a conjugate of the BACE1 inhibitor S-39 and SiR647, as a novel fluorogenic, tag-free, and antibody-free label for BACE1. We present its chemical development, characterize its photo-physical and pharmacologic properties, and evaluate its behavior in solution, in over-expression systems, and in native brain tissue. We demonstrate its applicability in confocal, stimulated emission depletion (STED), and dynamic single molecule microscopy. First functional studies with SiR-BACE1 on the surface mobility of BACE1 revealed a markedly confined diffusion pattern.

Vacuum ultraviolet photolysis of hydrogenated amorphous carbons. III. Diffusion of photo-produced H2 as a function of temperature

NASA Astrophysics Data System (ADS)

Martín-Doménech, R.; Dartois, E.; Muñoz Caro, G. M.

2016-06-01

Context. Hydrogenated amorphous carbon (a-C:H) has been proposed as one of the carbonaceous solids detected in the interstellar medium. Energetic processing of the a-C:H particles leads to the dissociation of the C-H bonds and the formation of hydrogen molecules and small hydrocarbons. Photo-produced H2 molecules in the bulk of the dust particles can diffuse out to the gas phase and contribute to the total H2 abundance. Aims: We have simulated this process in the laboratory with plasma-produced a-C:H and a-C:D analogs under astrophysically relevant conditions to investigate the dependence of the diffusion as a function of temperature. Methods: Experimental simulations were performed in a high-vacuum chamber, with complementary experiments carried out in an ultra-high-vacuum chamber. Plasma-produced a-C:H and a-C:D analogs were UV-irradiated using a microwave-discharged hydrogen flow lamp. Molecules diffusing to the gas-phase were detected by a quadrupole mass spectrometer, providing a measurement of the outgoing H2 or D2 flux. By comparing the experimental measurements with the expected flux from a one-dimensional diffusion model, a diffusion coefficient D could be derived for experiments carried out at different temperatures. Results: Dependence on the diffusion coefficient D with the temperature followed an Arrhenius-type equation. The activation energy for the diffusion process was estimated (ED(H2) = 1660 ± 110 K, ED(D2) = 2090 ± 90 K), as well as the pre-exponential factor (D0(H2) = 0.0007 cm2 s-1, D0(D2) = 0.0045 cm2 s-1). Conclusions: The strong decrease of the diffusion coefficient at low dust particle temperatures exponentially increases the diffusion times in astrophysical environments. Therefore, transient dust heating by cosmic rays needs to be invoked for the release of the photo-produced H2 molecules in cold photon-dominated regions, where destruction of the aliphatic component in hydrogenated amorphous carbons most probably takes place.

Diffusion and mobility of atomic particles in a liquid

NASA Astrophysics Data System (ADS)

Smirnov, B. M.; Son, E. E.; Tereshonok, D. V.

2017-11-01

The diffusion coefficient of a test atom or molecule in a liquid is determined for the mechanism where the displacement of the test molecule results from the vibrations and motion of liquid molecules surrounding the test molecule and of the test particle itself. This leads to a random change in the coordinate of the test molecule, which eventually results in the diffusion motion of the test particle in space. Two models parameters of interaction of a particle and a liquid are used to find the activation energy of the diffusion process under consideration: the gas-kinetic cross section for scattering of test molecules in the parent gas and the Wigner-Seitz radius for test molecules. In the context of this approach, we have calculated the diffusion coefficient of atoms and molecules in water, where based on experimental data, we have constructed the dependence of the activation energy for the diffusion of test molecules in water on the interaction parameter and the temperature dependence for diffusion coefficient of atoms or molecules in water within the models considered. The statistically averaged difference of the activation energies for the diffusion coefficients of different test molecules in water that we have calculated based on each of the presented models does not exceed 10% of the diffusion coefficient itself. We have considered the diffusion of clusters in water and present the dependence of the diffusion coefficient on the cluster size. The accuracy of the presented formulas for the diffusion coefficient of atomic particles in water is estimated to be 50%.

Diffusion and related transport mechanisms in brain tissue

NASA Astrophysics Data System (ADS)

Nicholson, Charles

2001-07-01

Diffusion plays a crucial role in brain function. The spaces between cells can be likened to the water phase of a foam and many substances move within this complicated region. Diffusion in this interstitial space can be accurately modelled with appropriate modifications of classical equations and quantified from measurements based on novel micro-techniques. Besides delivering glucose and oxygen from the vascular system to brain cells, diffusion also moves informational substances between cells, a process known as volume transmission. Deviations from expected results reveal how local uptake, degradation or bulk flow may modify the transport of molecules. Diffusion is also essential to many therapies that deliver drugs to the brain. The diffusion-generated concentration distributions of well-chosen molecules also reveal the structure of brain tissue. This structure is represented by the volume fraction (void space) and the tortuosity (hindrance to diffusion imposed by local boundaries or local viscosity). Analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. Theoretical and experimental approaches borrow from classical diffusion theory and from porous media concepts. Earlier studies were based on radiotracers but the recent methods use a point-source paradigm coupled with micro-sensors or optical imaging of macromolecules labelled with fluorescent tags. These concepts and methods are likely to be applicable elsewhere to measure diffusion properties in very small volumes of highly structured but delicate material.

Diffusion relaxation times of nonequilibrium isolated small bodies and their solid phase ensembles to equilibrium states

NASA Astrophysics Data System (ADS)

Tovbin, Yu. K.

2017-08-01

The possibility of obtaining analytical estimates in a diffusion approximation of the times needed by nonequilibrium small bodies to relax to their equilibrium states based on knowledge of the mass transfer coefficient is considered. This coefficient is expressed as the product of the self-diffusion coefficient and the thermodynamic factor. A set of equations for the diffusion transport of mixture components is formulated, characteristic scales of the size of microheterogeneous phases are identified, and effective mass transfer coefficients are constructed for them. Allowing for the developed interface of coexisting and immiscible phases along with the porosity of solid phases is discussed. This approach can be applied to the diffusion equalization of concentrations of solid mixture components in many physicochemical systems: the mutual diffusion of components in multicomponent systems (alloys, semiconductors, solid mixtures of inert gases) and the mass transfer of an absorbed mobile component in the voids of a matrix consisting of slow components or a mixed composition of mobile and slow components (e.g., hydrogen in metals, oxygen in oxides, and the transfer of molecules through membranes of different natures, including polymeric).

Rac1 Recruitment to the Archipelago Structure of the Focal Adhesion through the Fluid Membrane as Revealed by Single-Molecule Analysis

PubMed Central

Shibata, Akihiro C E; Chen, Limin H; Nagai, Rie; Ishidate, Fumiyoshi; Chadda, Rahul; Miwa, Yoshihiro; Naruse, Keiji; Shirai, Yuki M; Fujiwara, Takahiro K; Kusumi, Akihiro

2013-01-01

The focal adhesion (FA) is an integrin-based structure built in/on the plasma membrane (PM), linking the extracellular matrix to the actin stress-fibers, working as cell migration scaffolds. Previously, we proposed the archipelago architecture of the FA, in which FA largely consists of fluid membrane, dotted with small islands accumulating FA proteins: membrane molecules enter the inter-island channels in the FA zone rather freely, and the integrins in the FA-protein islands rapidly exchanges with those in the bulk membrane. Here, we examined how Rac1, a small G-protein regulating FA formation, and its activators αPIX and βPIX, are recruited to the FA zones. PIX molecules are recruited from the cytoplasm to the FA zones directly. In contrast, majorities of Rac1 molecules first arrive from the cytoplasm on the general inner PM surface, and then enter the FA zones via lateral diffusion on the PM, which is possible due to rapid Rac1 diffusion even within the FA zones, slowed only by a factor of two to four compared with that outside. The constitutively-active Rac1 mutant exhibited temporary and all-time immobilizations in the FA zone, suggesting that upon PIX-induced Rac1 activation at the FA-protein islands, Rac1 tends to be immobilized at the FA-protein islands. © 2013 Wiley Periodicals, Inc PMID:23341328

Pseudomonas aeruginosa and their small diffusible extracellular molecules inhibit Aspergillus fumigatus biofilm formation.

PubMed

Mowat, Eilidh; Rajendran, Ranjith; Williams, Craig; McCulloch, Elaine; Jones, Brian; Lang, Sue; Ramage, Gordon

2010-12-01

Aspergillus fumigatus is often isolated from the lungs of cystic fibrosis (CF) patients, but unlike in severely immunocompromised individuals, the mortality rates are low. This suggests that competition from bacteria within the CF lung may be inhibitory. The purpose of this study was to investigate how Pseudomonas aeruginosa influences A. fumigatus conidial germination and biofilm formation. Aspergillus fumigatus biofilm formation was inhibited by direct contact with P. aeruginosa, but had no effect on preformed biofilm. A secreted heat-stable soluble factor was also shown to exhibit biofilm inhibition. Coculture of P. aeruginosa quorum-sensing mutants (PAO1:ΔLasI, PAO1:ΔLasR) did not significantly inhibit A. fumigatus biofilms (52.6-58.8%) to the same extent as that of the PA01 wild type (22.9-30.1%), both by direct and by indirect interaction (P<0.001). Planktonic and sessile inhibition assays with a series of short carbon chain molecules (decanol, decanoic acid and dodecanol) demonstrated that these molecules could both inhibit and disrupt biofilms in a concentration-dependent manner. Overall, this suggests that small diffusible and heat-stable molecules may be responsible for the competitive inhibition of filamentous fungal growth in polymicrobial environments such as the CF lung. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Computational methods for diffusion-influenced biochemical reactions.

PubMed

Dobrzynski, Maciej; Rodríguez, Jordi Vidal; Kaandorp, Jaap A; Blom, Joke G

2007-08-01

We compare stochastic computational methods accounting for space and discrete nature of reactants in biochemical systems. Implementations based on Brownian dynamics (BD) and the reaction-diffusion master equation are applied to a simplified gene expression model and to a signal transduction pathway in Escherichia coli. In the regime where the number of molecules is small and reactions are diffusion-limited predicted fluctuations in the product number vary between the methods, while the average is the same. Computational approaches at the level of the reaction-diffusion master equation compute the same fluctuations as the reference result obtained from the particle-based method if the size of the sub-volumes is comparable to the diameter of reactants. Using numerical simulations of reversible binding of a pair of molecules we argue that the disagreement in predicted fluctuations is due to different modeling of inter-arrival times between reaction events. Simulations for a more complex biological study show that the different approaches lead to different results due to modeling issues. Finally, we present the physical assumptions behind the mesoscopic models for the reaction-diffusion systems. Input files for the simulations and the source code of GMP can be found under the following address: http://www.cwi.nl/projects/sic/bioinformatics2007/

Measurement of the eddy diffusion term in chromatographic columns. I. Application to the first generation of 4.6mm I.D. monolithic columns.

PubMed

Gritti, Fabrice; Guiochon, Georges

2011-08-05

The corrected heights equivalent to a theoretical plate (HETP) of three 4.6mm I.D. monolithic Onyx-C(18) columns (Onyx, Phenomenex, Torrance, CA) of different lengths (2.5, 5, and 10 cm) are reported for retained (toluene, naphthalene) and non-retained (uracil, caffeine) small molecules. The moments of the peak profiles were measured according to the accurate numerical integration method. Correction for the extra-column contributions was systematically applied. The peak parking method was used in order to measure the bulk diffusion coefficients of the sample molecules, their longitudinal diffusion terms, and the eddy diffusion term of the three monolithic columns. The experimental results demonstrate that the maximum efficiency was 60,000 plates/m for retained compounds. The column length has a large impact on the plate height of non-retained species. These observations were unambiguously explained by a large trans-column eddy diffusion term in the van Deemter HETP equation. This large trans-rod eddy diffusion term is due to the combination of a large trans-rod velocity bias (≃3%), a small radial dispersion coefficient in silica monolithic columns, and a poorly designed distribution and collection of the sample streamlets at the inlet and outlet of the monolithic rod. Improving the performance of large I.D. monolithic columns will require (1) a detailed knowledge of the actual flow distribution across and along these monolithic rod and (2) the design of appropriate inlet and outlet distributors designed to minimize the nefarious impact of the radial flow heterogeneity on band broadening. Copyright © 2011 Elsevier B.V. All rights reserved.

Accurate anharmonic zero-point energies for some combustion-related species from diffusion Monte Carlo

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

Harding, Lawrence B.; Georgievskii, Yuri; Klippenstein, Stephen J.

Full dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ calculations have been determined for 48 small combustion related molecules. The analytic surfaces have been used in Diffusion Monte Carlo calculations of the anharmonic, zero point energies. Here, the resulting anharmonicity corrections are compared to vibrational perturbation theory results based both on the same level of electronic structure theory and on lower level electronic structure methods (B3LYP and MP2).

Accurate Anharmonic Zero-Point Energies for Some Combustion-Related Species from Diffusion Monte Carlo.

PubMed

Harding, Lawrence B; Georgievskii, Yuri; Klippenstein, Stephen J

2017-06-08

Full-dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ calculations have been determined for 48 small combustion-related molecules. The analytic surfaces have been used in Diffusion Monte Carlo calculations of the anharmonic zero-point energies. The resulting anharmonicity corrections are compared to vibrational perturbation theory results based both on the same level of electronic structure theory and on lower-level electronic structure methods (B3LYP and MP2).

Accurate anharmonic zero-point energies for some combustion-related species from diffusion Monte Carlo

DOE PAGES

Harding, Lawrence B.; Georgievskii, Yuri; Klippenstein, Stephen J.

2017-05-17

Full dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ calculations have been determined for 48 small combustion related molecules. The analytic surfaces have been used in Diffusion Monte Carlo calculations of the anharmonic, zero point energies. Here, the resulting anharmonicity corrections are compared to vibrational perturbation theory results based both on the same level of electronic structure theory and on lower level electronic structure methods (B3LYP and MP2).

Macromolecule diffusion and confinement in prokaryotic cells.

PubMed

Mika, Jacek T; Poolman, Bert

2011-02-01

We review recent observations on the mobility of macromolecules and their spatial organization in live bacterial cells. We outline the major fluorescence microscopy-based methods to determine the mobility and thus the diffusion coefficients (D) of molecules, which is not trivial in small cells. The extremely high macromolecule crowding of prokaryotes is used to rationalize the reported lower diffusion coefficients as compared to eukaryotes, and we speculate on the nature of the barriers for diffusion observed for proteins (and mRNAs) in vivo. Building on in vitro experiments and modeling studies, we evaluate the size dependence of diffusion coefficients for macromolecules in vivo, in case of both water-soluble and integral membrane proteins. We comment on the possibilities of anomalous diffusion and provide examples where the macromolecule mobility may be limiting biological processes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Molecular Dynamics Simulations of Hydration Effects on Solvation, Diffusivity, and Permeability in Chitosan/Chitin Films.

PubMed

McDonnell, Marshall T; Greeley, Duncan A; Kit, Kevin M; Keffer, David J

2016-09-01

The effects of hydration on the solvation, diffusivity, solubility, and permeability of oxygen molecules in sustainable, biodegradable chitosan/chitin food packaging films were studied via molecular dynamics and confined random walk simulations. With increasing hydration, the membrane has a more homogeneous water distribution with the polymer chains being fully solvated. The diffusivity increased by a factor of 4 for oxygen molecules and by an order of magnitude for water with increasing the humidity. To calculate the Henry's constant and solubility of oxygen in the membranes with changing hydration, the excess chemical potential was calculated via free energy perturbation, thermodynamic integration and direct particle deletion methods. The simulations predicted a higher solubility and permeability for the lower humidity, in contradiction to experimental results. All three methods for calculating the solubility were in good agreement. It was found that the Coulombic interactions in the potential caused the oxygen to bind too strongly to the protonated amine group. Insight from this work will help guide molecular modeling of chitosan/chitin membranes, specifically permeability measurements for small solute molecules. Efforts to chemically tailor chitosan/chitin membranes to favor discrete as opposed to continuous aqueous domains could reduce oxygen permeability.

Spatial averaging for small molecule diffusion in condensed phase environments

NASA Astrophysics Data System (ADS)

Plattner, Nuria; Doll, J. D.; Meuwly, Markus

2010-07-01

Spatial averaging is a new approach for sampling rare-event problems. The approach modifies the importance function which improves the sampling efficiency while keeping a defined relation to the original statistical distribution. In this work, spatial averaging is applied to multidimensional systems for typical problems arising in physical chemistry. They include (I) a CO molecule diffusing on an amorphous ice surface, (II) a hydrogen molecule probing favorable positions in amorphous ice, and (III) CO migration in myoglobin. The systems encompass a wide range of energy barriers and for all of them spatial averaging is found to outperform conventional Metropolis Monte Carlo. It is also found that optimal simulation parameters are surprisingly similar for the different systems studied, in particular, the radius of the point cloud over which the potential energy function is averaged. For H2 diffusing in amorphous ice it is found that facile migration is possible which is in agreement with previous suggestions from experiment. The free energy barriers involved are typically lower than 1 kcal/mol. Spatial averaging simulations for CO in myoglobin are able to locate all currently characterized metastable states. Overall, it is found that spatial averaging considerably improves the sampling of configurational space.

Model of the initiation of signal transduction by ligands in a cell culture: Simulation of molecules near a plane membrane comprising receptors

NASA Astrophysics Data System (ADS)

Plante, Ianik; Cucinotta, Francis A.

2011-11-01

Cell communication is a key mechanism in tissue responses to radiation. Several molecules are implicated in radiation-induced signaling between cells, but their contributions to radiation risk are poorly understood. Meanwhile, Green's functions for diffusion-influenced reactions have appeared in the literature, which are applied to describe the diffusion of molecules near a plane membrane comprising bound receptors with the possibility of reversible binding of a ligand and activation of signal transduction proteins by the ligand-receptor complex. We have developed Brownian dynamics algorithms to simulate particle histories in this system which can accurately reproduce the theoretical distribution of distances of a ligand from the membrane, the number of reversibly bound particles, and the number of receptor complexes activating signaling proteins as a function of time, regardless of the number of time steps used for the simulation. These simulations will be of great importance to model interactions at low doses where stochastic effects induced by a small number of molecules or interactions come into play.

Effect of Annealing on Exciton Diffusion in a High Performance Small Molecule Organic Photovoltaic Material.

PubMed

Long, Yun; Hedley, Gordon J; Ruseckas, Arvydas; Chowdhury, Mithun; Roland, Thomas; Serrano, Luis A; Cooke, Graeme; Samuel, Ifor D W

2017-05-03

Singlet exciton diffusion was studied in the efficient organic photovoltaic electron donor material DTS(FBTTh 2 ) 2 . Three complementary time-resolved fluorescence measurements were performed: quenching in planar heterojunctions with an electron acceptor, exciton-exciton annihilation, and fluorescence depolarization. The average exciton diffusivity increases upon annealing from 1.6 × 10 -3 to 3.6 × 10 -3 cm 2 s -1 , resulting in an enhancement of the mean two-dimensional exciton diffusion length (L D = (4Dτ) 1/2 ) from 15 to 27 nm. About 30% of the excitons get trapped very quickly in as-cast films. The high exciton diffusion coefficient of the material leads to it being able to harvest excitons efficiently from large donor domains in bulk heterojunctions.

Effect of Annealing on Exciton Diffusion in a High Performance Small Molecule Organic Photovoltaic Material

PubMed Central

2017-01-01

Singlet exciton diffusion was studied in the efficient organic photovoltaic electron donor material DTS(FBTTh2)2. Three complementary time-resolved fluorescence measurements were performed: quenching in planar heterojunctions with an electron acceptor, exciton–exciton annihilation, and fluorescence depolarization. The average exciton diffusivity increases upon annealing from 1.6 × 10–3 to 3.6 × 10–3 cm2 s–1, resulting in an enhancement of the mean two-dimensional exciton diffusion length (LD = (4Dτ)1/2) from 15 to 27 nm. About 30% of the excitons get trapped very quickly in as-cast films. The high exciton diffusion coefficient of the material leads to it being able to harvest excitons efficiently from large donor domains in bulk heterojunctions. PMID:28358189

Regulation of Endothelial Adherens Junctions by Tyrosine Phosphorylation

PubMed Central

Adam, Alejandro Pablo

2015-01-01

Endothelial cells form a semipermeable, regulated barrier that limits the passage of fluid, small molecules, and leukocytes between the bloodstream and the surrounding tissues. The adherens junction, a major mechanism of intercellular adhesion, is comprised of transmembrane cadherins forming homotypic interactions between adjacent cells and associated cytoplasmic catenins linking the cadherins to the cytoskeleton. Inflammatory conditions promote the disassembly of the adherens junction and a loss of intercellular adhesion, creating openings or gaps in the endothelium through which small molecules diffuse and leukocytes transmigrate. Tyrosine kinase signaling has emerged as a central regulator of the inflammatory response, partly through direct phosphorylation and dephosphorylation of the adherens junction components. This review discusses the findings that support and those that argue against a direct effect of cadherin and catenin phosphorylation in the disassembly of the adherens junction. Recent findings indicate a complex interaction between kinases, phosphatases, and the adherens junction components that allow a fine regulation of the endothelial permeability to small molecules, leukocyte migration, and barrier resealing. PMID:26556953

Effects of Small Polar Molecules (MA+ and H2O) on Degradation Processes of Perovskite Solar Cells.

PubMed

Ma, Chunqing; Shen, Dong; Qing, Jian; Thachoth Chandran, Hrisheekesh; Lo, Ming-Fai; Lee, Chun-Sing

2017-05-03

Degradation mechanisms of methylammonium lead halide perovskite solar cells (PSCs) have drawn much attention recently. Herein, the bulk and surface degradation processes of the perovskite were differentiated for the first time by employing combinational studies using electrochemical impedance spectroscopy (EIS), capacitance frequency (CF), and X-ray diffraction (XRD) studies with particular attention on the roles of small polar molecules (MA + and H 2 O). CF study shows that short-circuit current density of the PSCs is increased by H 2 O at the beginning of the degradation process coupled with an increased surface capacitance. On the basis of EIS and XRD analysis, we show that the bulk degradation of PSCs involves a lattice expansion process, which facilitates MA + ion diffusion by creating more efficient channels. These results provide a better understanding of the roles of small polar molecules on degradation processes in the bulk and on the surface of the perovskite film.

Growth Of Organic Semiconductor Thin Films with Multi-Micron Domain Size and Fabrication of Organic Transistors Using a Stencil Nanosieve.

PubMed

Fesenko, Pavlo; Flauraud, Valentin; Xie, Shenqi; Kang, Enpu; Uemura, Takafumi; Brugger, Jürgen; Genoe, Jan; Heremans, Paul; Rolin, Cédric

2017-07-19

To grow small molecule semiconductor thin films with domain size larger than modern-day device sizes, we evaporate the material through a dense array of small apertures, called a stencil nanosieve. The aperture size of 0.5 μm results in low nucleation density, whereas the aperture-to-aperture distance of 0.5 μm provides sufficient crosstalk between neighboring apertures through the diffusion of adsorbed molecules. By integrating the nanosieve in the channel area of a thin-film transistor mask, we show a route for patterning both the organic semiconductor and the metal contacts of thin-film transistors using one mask only and without mask realignment.

Measurement of diffusion coefficients from solution rates of bubbles

NASA Technical Reports Server (NTRS)

Krieger, I. M.

1979-01-01

The rate of solution of a stationary bubble is limited by the diffusion of dissolved gas molecules away from the bubble surface. Diffusion coefficients computed from measured rates of solution give mean values higher than accepted literature values, with standard errors as high as 10% for a single observation. Better accuracy is achieved with sparingly soluble gases, small bubbles, and highly viscous liquids. Accuracy correlates with the Grashof number, indicating that free convection is the major source of error. Accuracy should, therefore, be greatly increased in a gravity-free environment. The fact that the bubble will need no support is an additional important advantage of Spacelab for this measurement.

Thin Film Mediated Phase Change Phenomena: Crystallization, Evaporation and Wetting

NASA Technical Reports Server (NTRS)

Wettlaufer, John S.

1998-01-01

We focus on two distinct materials science problems that arise in two distinct microgravity environments: In space and within the space of a polymeric network. In the former environment, we consider a near eutectic alloy film in contact with its vapor which, when evaporating on earth, will experience compositionally induced buoyancy driven convection. The latter will significantly influence the morphology of the crystallized end member. In the absence of gravity, the morphology will be dominated by molecular diffusion and Marangoni driven viscous flow, and we study these phenomena theoretically and experimentally. The second microgravity environment exists in liquids, gels, and other soft materials where the small mass of individual molecules makes the effect of gravity negligible next to the relatively strong forces of intermolecular collisions. In such materials, an essential question concerns how to relate the molecular dynamics to the bulk rheological behavior. Here, we observe experimentally the diffusive motion of a single molecule in a single polymer filament, embedded within a polymer network and find anomalous diffusive behavior.

Blue Luminescence and Extended Red Emission: Possible Connections to the Diffuse Interstellar Bands

NASA Astrophysics Data System (ADS)

Witt, A. N.

2014-02-01

Blue luminescence (BL) and extended red emission (ERE) are observed as diffuse, optical-wavelength emissions in interstellar space, resulting from photoluminescence by ultraviolet(UV)-illuminated interstellar grains. Faintness and the challenge of separating the BL and ERE from the frequently much brighter dust-scattered continuum present major observational hurdles, which have permitted only slow progress in testing the numerous models that have been advanced to explain these two phenomena. Both the ERE, peaking near 680 nm (FWHM ~ 60 - 120 nm) and the BL, asymmetrically peaking at ~ 378 nm (FWHM ~ 45 nm), were first discovered in the Red Rectangle nebula. Subsequently, ERE and BL have been observed in other reflection nebulae, and in the case of the ERE, in carbon-rich planetary nebulae, H II regions, high-latitude cirrus clouds, the galactic diffuse ISM, and in external galaxies. BL exhibits a close spatial and intensity correlation with emission in the aromatic emission feature at 3.3 micron, most likely arising from small, neutral polycyclic aromatic hydrocarbon (PAH) molecules. The spectral characteristics of the BL also agree with those of fluorescence by PAH molecules with 13 to 19 carbon atoms. The BL phenomenon is thus most readily understood as the optical fluorescence of small, UV-excited aromatic molecules. The ERE, by contrast, though co-existent with mid-IR PAH emissions, does not correlate with emissions from either neutral or ionized PAHs. Instead, the spatial ERE morphology appears to be strictly governed by the density of far-UV (E >= 10.5 eV) photons, which are required for the ERE excitation. The most restrictive observational constraint for the ERE process is its exceptionally high quantum efficiency. If the ERE results from photo-excitation of a nano-particle carrier by photons with E >= 10.5 eV in a single-step process, the quantum efficiency exceeds 100%. Such a process, in which one to three low-energy optical photons may be emitted following a single far-UV excitation, is possible in highly isolated small clusters, e.g. small, dehydrogenated carbon clusters with about 20 to 28 carbon atoms. A possible connection between the ERE carriers and the carriers of DIBs may exist in that both are ubiquitous throughout the diffuse interstellar medium and both have an abundance of low-lying electronic levels with E <= 2.3 eV above the ground state.

Computer Simulations of Small Molecules in Membranes: Insights from Computer Simulations into the Interactions of Small Molecules with Lipid Bilayers

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; New, Michael H.; Schweighofer, Karl; Wilson, Michael A.; DeVincenzi, Donald L. (Technical Monitor)

2000-01-01

Two of Ernest Overton's lasting contributions to biology are the Meyer-Overton relationship between the potency of an anesthetic and its solubility in oil, and the Overton rule which relates the permeability of a membrane to the oil-water partition coefficient of the permeating molecule. A growing body of experimental evidence, however, cannot be reconciled with these theories. In particular, the molecular nature of membranes, unknown to Overton, needs to be included in any description of these phenomena. Computer simulations are ideally suited for providing atomic-level information about the behavior of small molecules in membranes. The authors discuss simulation studies relevant to Overton's ideas. Through simulations it was found that anesthetics tend to concentrate at interfaces and their anesthetic potency correlates better with solubility at the water-membrane interface than with solubility in oil. Simulation studies of membrane permeation revealed the anisotropic nature of the membranes, as evidenced, for example, by the highly nonuniform distribution of free volume in the bilayer. This, in turn, influences the diffusion rates of solutes, which increase with the depth in the membrane. Small solutes tend to move by hopping between voids in the bilayer, and this hopping motion may be responsible for the deviation from the Overton rule of the permeation rates of these molecules.

First-principles analysis of C2H2 molecule diffusion and its dissociation process on the ferromagnetic bcc-Fe110 surface.

PubMed

Ikeda, Minoru; Yamasaki, Takahiro; Kaneta, Chioko

2010-09-29

Using the projector-augmented plane wave method, we study diffusion and dissociation processes of C(2)H(2) molecules on the ferromagnetic bcc-Fe(110) surface and investigate the formation process of graphene created by C(2)H(2) molecules. The most stable site for C(2)H(2) on the Fe surface is a hollow site and its adsorption energy is - 3.5 eV. In order to study the diffusion process of the C(2)H(2) molecule, the barrier height energies for the C atom, C(2)-dimer and CH as well as the C(2)H(2) molecule are estimated using the nudged elastic band method. The barrier height energy for C(2)H(2) is 0.71 eV and this indicates that the C(2)H(2) diffuses easily on this FM bcc-Fe(110) surface. We further investigate the two step dissociation process of C(2)H(2) on Fe. The first step is the dissociation of C(2)H(2) into C(2)H and H, and the second step is that of C(2)H into C(2) and H. Their dissociation energies are 0.9 and 1.2 eV, respectively. These energies are relatively small compared to the dissociation energy 7.5 eV of C(2)H(2) into C(2)H and H in the vacuum. Thus, the Fe surface shows catalytic effects. We further investigate the initial formation process of graphene by increasing the coverage of C(2)H(2). The formation process of the benzene molecule on the FM bcc(110) surface is also discussed. We find that there exists a critical coverage of C(2)H(2) which characterizes the beginning of the formation of the graphene.

Photogenerated Intrinsic Free Carriers in Small-molecule Organic Semiconductors Visualized by Ultrafast Spectroscopy

PubMed Central

He, Xiaochuan; Zhu, Gangbei; Yang, Jianbing; Chang, Hao; Meng, Qingyu; Zhao, Hongwu; Zhou, Xin; Yue, Shuai; Wang, Zhuan; Shi, Jinan; Gu, Lin; Yan, Donghang; Weng, Yuxiang

2015-01-01

Confirmation of direct photogeneration of intrinsic delocalized free carriers in small-molecule organic semiconductors has been a long-sought but unsolved issue, which is of fundamental significance to its application in photo-electric devices. Although the excitonic description of photoexcitation in these materials has been widely accepted, this concept is challenged by recently reported phenomena. Here we report observation of direct delocalized free carrier generation upon interband photoexcitation in highly crystalline zinc phthalocyanine films prepared by the weak epitaxy growth method using ultrafast spectroscopy. Transient absorption spectra spanning the visible to mid-infrared region revealed the existence of short-lived free electrons and holes with a diffusion length estimated to cross at least 11 molecules along the π−π stacking direction that subsequently localize to form charge transfer excitons. The interband transition was evidenced by ultraviolet-visible absorption, photoluminescence and electroluminescence spectroscopy. Our results suggest that delocalized free carriers photogeneration can also be achieved in organic semiconductors when the molecules are packed properly. PMID:26611323

Optimization of cell morphology measurement via single-molecule tracking PALM.

PubMed

Frost, Nicholas A; Lu, Hsiangmin E; Blanpied, Thomas A

2012-01-01

In neurons, the shape of dendritic spines relates to synapse function, which is rapidly altered during experience-dependent neural plasticity. The small size of spines makes detailed measurement of their morphology in living cells best suited to super-resolution imaging techniques. The distribution of molecular positions mapped via live-cell Photoactivated Localization Microscopy (PALM) is a powerful approach, but molecular motion complicates this analysis and can degrade overall resolution of the morphological reconstruction. Nevertheless, the motion is of additional interest because tracking single molecules provides diffusion coefficients, bound fraction, and other key functional parameters. We used Monte Carlo simulations to examine features of single-molecule tracking of practical utility for the simultaneous determination of cell morphology. We find that the accuracy of determining both distance and angle of motion depend heavily on the precision with which molecules are localized. Strikingly, diffusion within a bounded region resulted in an inward bias of localizations away from the edges, inaccurately reflecting the region structure. This inward bias additionally resulted in a counterintuitive reduction of measured diffusion coefficient for fast-moving molecules; this effect was accentuated by the long camera exposures typically used in single-molecule tracking. Thus, accurate determination of cell morphology from rapidly moving molecules requires the use of short integration times within each image to minimize artifacts caused by motion during image acquisition. Sequential imaging of neuronal processes using excitation pulses of either 2 ms or 10 ms within imaging frames confirmed this: processes appeared erroneously thinner when imaged using the longer excitation pulse. Using this pulsed excitation approach, we show that PALM can be used to image spine and spine neck morphology in living neurons. These results clarify a number of issues involved in interpretation of single-molecule data in living cells and provide a method to minimize artifacts in single-molecule experiments.

Interplay between translational diffusion and large-amplitude angular jumps of water molecules

NASA Astrophysics Data System (ADS)

Liu, Chao; Zhang, Yangyang; Zhang, Jian; Wang, Jun; Li, Wenfei; Wang, Wei

2018-05-01

Understanding the microscopic mechanism of water molecular translational diffusion is a challenging topic in both physics and chemistry. Here, we report an investigation on the interplay between the translational diffusion and the large-amplitude angular jumps of water molecules in bulk water using molecular dynamics simulations. We found that large-amplitude angular jumps are tightly coupled to the translational diffusions. Particularly, we revealed that concurrent rotational jumps of spatially neighboring water molecules induce inter-basin translational jumps, which contributes to the fast component of the water translational diffusion. Consequently, the translational diffusion shows positional heterogeneity; i.e., the neighbors of the water molecules with inter-basin translational jumps have larger probability to diffuse by inter-basin translational jumps. Our control simulations showed that a model water molecule with moderate hydrogen bond strength can diffuse much faster than a simple Lennard-Jones particle in bulk water due to the capability of disturbing the hydrogen bond network of the surrounding water molecules. Our results added to the understanding of the microscopic picture of the water translational diffusion and demonstrated the unique features of water diffusion arising from their hydrogen bond network structure compared with those of the simple liquids.

Spin relaxation measurements of electrostatic bias in intermolecular exploration

NASA Astrophysics Data System (ADS)

Teng, Ching-Ling; Bryant, Robert G.

2006-04-01

We utilize the paramagnetic contribution to proton spin-lattice relaxation rate constants induced by freely diffusing charged paramagnetic centers to investigate the effect of charge on the intermolecular exploration of a protein by the small molecule. The proton NMR spectrum provided 255 resolved resonances that report how the explorer molecule local concentration varies with position on the surface. The measurements integrate over local dielectric constant variations, and, in principle, provide an experimental characterization of the surface free energy sampling biases introduced by the charge distribution on the protein. The experimental results for ribonuclease A obtained using positive, neutral, and negatively charged small nitroxide radicals are qualitatively similar to those expected from electrostatic calculations. However, while systematic electrostatic trends are apparent, the three different combinations of the data sets do not yield internally consistent values for the electrostatic contribution to the intermolecular free energy. We attribute this failure to the weakness of the electrostatic sampling bias for charged nitroxides in water and local variations in effective translational diffusion constant at the water-protein interface, which enters the nuclear spin relaxation equations for the nitroxide-proton dipolar coupling.

Restricted ADP movement in cardiomyocytes: Cytosolic diffusion obstacles are complemented with a small number of open mitochondrial voltage-dependent anion channels.

PubMed

Simson, Päivo; Jepihhina, Natalja; Laasmaa, Martin; Peterson, Pearu; Birkedal, Rikke; Vendelin, Marko

2016-08-01

Adequate intracellular energy transfer is crucial for proper cardiac function. In energy starved failing hearts, partial restoration of energy transfer can rescue mechanical performance. There are two types of diffusion obstacles that interfere with energy transfer from mitochondria to ATPases: mitochondrial outer membrane (MOM) with voltage-dependent anion channel (VDAC) permeable to small hydrophilic molecules and cytoplasmatic diffusion barriers grouping ATP-producers and -consumers. So far, there is no method developed to clearly distinguish the contributions of cytoplasmatic barriers and MOM to the overall diffusion restriction. Furthermore, the number of open VDACs in vivo remains unknown. The aim of this work was to establish the partitioning of intracellular diffusion obstacles in cardiomyocytes. We studied the response of mitochondrial oxidative phosphorylation of permeabilized rat cardiomyocytes to changes in extracellular ADP by recording 3D image stacks of NADH autofluorescence. Using cell-specific mathematical models, we determined the permeability of MOM and cytoplasmatic barriers. We found that only ~2% of VDACs are accessible to cytosolic ADP and cytoplasmatic diffusion barriers reduce the apparent diffusion coefficient by 6-10×. In cardiomyocytes, diffusion barriers in the cytoplasm and by the MOM restrict ADP/ATP diffusion to similar extents suggesting a major role of both barriers in energy transfer and other intracellular processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of charge on encapsulation and release behavior of small molecules in self-assembled layer-by-layer microcapsules.

PubMed

Mandapalli, Praveen K; Labala, Suman; Vanamala, Deekshith; Koranglekar, Manali P; Sakimalla, Lakshmi A; Venuganti, Venkata Vamsi K

2014-12-01

The objective of this study is to investigate the influence of charge of model small molecules on their encapsulation and release behavior in layer-by-layer microcapsules (LbL-MC). Poly(styrene sulfonate) and poly(ethylene imine) were sequentially adsorbed on calcium carbonate sacrificial templates to prepare LbL-MC. Model molecules with varying charge, anionic - ascorbic acid, cationic - imatinib mesylate (IM) and neutral - 5-fluorouracil were encapsulated in LbL-MC. Free and encapsulated LbL-MC were characterized using zetasizer, FTIR spectroscope and differential scanning calorimeter. The influence of IM-loaded LbL-MC on cell viability was studied in B16F10 murine melanoma cells. Furthermore, biodistribution of IM-loaded LbL-MC with and without PEGylation was studied in BALB/c mice. Results showed spherical LbL-MC of 3.0 ± 0.4 μm diameter. Encapsulation efficiency of LbL-MC increased linearly (R(2 )= 0.89-0.99) with the increase in solute concentration. Increase in pH from 2 to 6 increased the encapsulation of charged molecules in LbL-MC. Charged molecules showed greater encapsulation efficiency in LbL-MC compared with neutral molecule. In vitro release kinetics showed Fickian and non-Fickian diffusion of small molecules, depending on the nature of molecular interactions with LbL-MC. At 50 μM concentration, free IM showed significantly (p < 0.05) more cytotoxicity compared with IM-loaded LbL-MC. Biodistribution studies showed that PEGylation of LbL-MC decreased the liver and spleen uptake of IM-encapsulated LbL-MC. In conclusion, LbL-MC can be developed as a potential carrier for small molecules depending on their physical and chemical properties.

Effective diffusion coefficient including the Marangoni effect

NASA Astrophysics Data System (ADS)

Kitahata, Hiroyuki; Yoshinaga, Natsuhiko

2018-04-01

Surface-active molecules supplied from a particle fixed at the water surface create a spatial gradient of the molecule concentration, resulting in Marangoni convection. Convective flow transports the molecules far from the particle, enhancing diffusion. We analytically derive the effective diffusion coefficient associated with the Marangoni convection rolls. The resulting estimated effective diffusion coefficient is consistent with our numerical results and the apparent diffusion coefficient measured in experiments.

Single-molecule diffusion and conformational dynamics by spatial integration of temporal fluctuations

PubMed Central

Serag, Maged F.; Abadi, Maram; Habuchi, Satoshi

2014-01-01

Single-molecule localization and tracking has been used to translate spatiotemporal information of individual molecules to map their diffusion behaviours. However, accurate analysis of diffusion behaviours and including other parameters, such as the conformation and size of molecules, remain as limitations to the method. Here, we report a method that addresses the limitations of existing single-molecular localization methods. The method is based on temporal tracking of the cumulative area occupied by molecules. These temporal fluctuations are tied to molecular size, rates of diffusion and conformational changes. By analysing fluorescent nanospheres and double-stranded DNA molecules of different lengths and topological forms, we demonstrate that our cumulative-area method surpasses the conventional single-molecule localization method in terms of the accuracy of determined diffusion coefficients. Furthermore, the cumulative-area method provides conformational relaxation times of structurally flexible chains along with diffusion coefficients, which together are relevant to work in a wide spectrum of scientific fields. PMID:25283876

Novel immunoassay formats for integrated microfluidic circuits: diffusion immunoassays (DIA)

NASA Astrophysics Data System (ADS)

Weigl, Bernhard H.; Hatch, Anson; Kamholz, Andrew E.; Yager, Paul

2000-03-01

Novel designs of integrated fluidic microchips allow separations, chemical reactions, and calibration-free analytical measurements to be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples. This technology lends itself to applications such as clinical diagnostics, including tumor marker screening, and environmental sensing in remote locations. Lab-on-a-Chip based systems offer many *advantages over traditional analytical devices: They consume extremely low volumes of both samples and reagents. Each chip is inexpensive and small. The sampling-to-result time is extremely short. They perform all analytical functions, including sampling, sample pretreatment, separation, dilution, and mixing steps, chemical reactions, and detection in an integrated microfluidic circuit. Lab-on-a-Chip systems enable the design of small, portable, rugged, low-cost, easy to use, yet extremely versatile and capable diagnostic instruments. In addition, fluids flowing in microchannels exhibit unique characteristics ('microfluidics'), which allow the design of analytical devices and assay formats that would not function on a macroscale. Existing Lab-on-a-chip technologies work very well for highly predictable and homogeneous samples common in genetic testing and drug discovery processes. One of the biggest challenges for current Labs-on-a-chip, however, is to perform analysis in the presence of the complexity and heterogeneity of actual samples such as whole blood or contaminated environmental samples. Micronics has developed a variety of Lab-on-a-Chip assays that can overcome those shortcomings. We will now present various types of novel Lab- on-a-Chip-based immunoassays, including the so-called Diffusion Immunoassays (DIA) that are based on the competitive laminar diffusion of analyte molecules and tracer molecules into a region of the chip containing antibodies that target the analyte molecules. Advantages of this technique are a reduction in reagents, higher sensitivity, minimal preparation of complex samples such as blood, real-time calibration, and extremely rapid analysis.

Molecular self-assembly for biological investigations and nanoscale lithography

NASA Astrophysics Data System (ADS)

Cheunkar, Sarawut

Small, diffusible molecules when recognized by their binding partners, such as proteins and antibodies, trigger enzymatic activity, cell communication, and immune response. Progress in analytical methods enabling detection, characterization, and visualization of biological dynamics at the molecular level will advance our exploration of complex biological systems. In this dissertation, analytical platforms were fabricated to capture membrane-associated receptors, which are essential proteins in cell signaling pathways. The neurotransmitter serotonin and its biological precursor were immobilized on gold substrates coated with self-assembled monolayers (SAMs) of oligo(ethylene glycol)alkanethiols and their reactive derivatives. The SAM-coated substrates present the biologically selective affinity of immobilized molecules to target native membrane-associated receptors. These substrates were also tested for biospecificity using antibodies. In addition, small-molecule-functionalized platforms, expressing neurotransmitter pharmacophores, were employed to examine kinetic interactions between G-protein-coupled receptors and their associated neurotransmitters. The binding interactions were monitored using a quartz crystal microbalance equipped with liquid-flow injection. The interaction kinetics of G-protein-coupled serotonin 1A receptor and 5-hydroxytyptophan-functionalized surfaces were studied in a real-time, label-free environment. Key binding parameters, such as equilibrium dissociation constants, binding rate constants, and dissociative half-life, were extracted. These parameters are critical for understanding and comparing biomolecular interactions in modern biomedical research. By integrating self-assembly, surface functionalization, and nanofabrication, small-molecule microarrays were created for high-throughput screening. A hybrid soft-lithography, called microcontact insertion printing, was used to pattern small molecules at the dilute scales necessary for highly selective biorecognition. By carefully tuning the polar surface energy of polymeric stamps, problems associated with patterning hydrophilic tether molecules inserted into hydrophilic preformed SAMs are surmounted. The patterned substrates presenting neurotransmitter precursors selectively capture membrane-associated receptors. These advances provide new avenues for fabricating small-molecule arrays. Furthermore, a novel strategy based on a conventional microcontact printing, called chemical lift-off lithography, was invented to overcome the micrometer-scale resolution limits of molecular ink diffusion in soft lithography. Self-assembled monolayers of hydroxyl-terminated alkanethiols, preformed on gold substrates, were selectively removed by oxygen-plasma-treated polymeric stamps in a subtractive stamping process with high pattern fidelity. The covalent interactions formed at the stamp-substrate interface are believed to be responsible for removing not only alkanethiol molecules but also a monolayer of gold atoms from the substrates. A variety of high-resolution patterned features were fabricated, and stamps were cleaned and reused many times without feature deterioration. The remaining SAMs acted as resists for etching exposed gold features. Monolayer backfilling into lifted-off areas enabled patterned protein capture, and 40-nanometer chemical patterns were achieved.

Diffusivity measurements of volatile organics in levitated viscous aerosol particles

NASA Astrophysics Data System (ADS)

Bastelberger, Sandra; Krieger, Ulrich K.; Luo, Beiping; Peter, Thomas

2017-07-01

Field measurements indicating that atmospheric secondary organic aerosol (SOA) particles can be present in a highly viscous, glassy state have spurred numerous studies addressing low diffusivities of water in glassy aerosols. The focus of these studies is on kinetic limitations of hygroscopic growth and the plasticizing effect of water. In contrast, much less is known about diffusion limitations of organic molecules and oxidants in viscous matrices. These may affect atmospheric chemistry and gas-particle partitioning of complex mixtures with constituents of different volatility. In this study, we quantify the diffusivity of a volatile organic in a viscous matrix. Evaporation of single particles generated from an aqueous solution of sucrose and small amounts of volatile tetraethylene glycol (PEG-4) is investigated in an electrodynamic balance at controlled relative humidity (RH) and temperature. The evaporative loss of PEG-4 as determined by Mie resonance spectroscopy is used in conjunction with a radially resolved diffusion model to retrieve translational diffusion coefficients of PEG-4. Comparison of the experimentally derived diffusivities with viscosity estimates for the ternary system reveals a breakdown of the Stokes-Einstein relationship, which has often been invoked to infer diffusivity from viscosity. The evaporation of PEG-4 shows pronounced RH and temperature dependencies and is severely depressed for RH ≲ 30 %, corresponding to diffusivities < 10-14 cm2 s-1 at temperatures < 15 °C. The temperature dependence is strong, suggesting a diffusion activation energy of about 300 kJ mol-1. We conclude that atmospheric volatile organic compounds can be subject to severe diffusion limitations in viscous organic aerosol particles. This may enable an important long-range transport mechanism for organic material, including pollutant molecules such as polycyclic aromatic hydrocarbons (PAHs).

Using Perturbation Theory to Compute the Morphological Similarity of Diffusion Tensors

PubMed Central

Bansal, Ravi; Staib, Lawrence H.; Xu, Dongrong; Laine, Andrew F.; Royal, Jason; Peterson, Bradley S.

2008-01-01

Computing the morphological similarity of Diffusion Tensors (DTs) at neighboring voxels within a DT image, or at corresponding locations across different DT images, is a fundamental and ubiquitous operation in the post-processing of DT images. The morphological similarity of DTs typically has been computed using either the Principal Directions (PDs) of DTs (i.e., the direction along which water molecules diffuse preferentially) or their tensor elements. Although comparing PDs allows the similarity of one morphological feature of DTs to be visualized directly in eigenspace, this method takes into account only a single eigenvector, and it is therefore sensitive to the presence of noise in the images that can introduce error into the estimation of that vector. Although comparing tensor elements, rather than PDs, is comparatively more robust to the effects of noise, the individual elements of a given tensor do not directly reflect the diffusion properties of water molecules. We propose a measure for computing the morphological similarity of DTs that uses both their eigenvalues and eigenvectors, and that also accounts for the noise levels present in DT images. Our measure presupposes that DTs in a homogeneous region within or across DT images are random perturbations of one another in the presence of noise. The similarity values that are computed using our method are smooth (in the sense that small changes in eigenvalues and eigenvectors cause only small changes in similarity), and they are symmetric when differences in eigenvalues and eigenvectors are also symmetric. In addition, our method does not presuppose that the corresponding eigenvectors across two DTs have been identified accurately, an assumption that is problematic in the presence of noise. Because we compute the similarity between DTs using their eigenspace components, our similarity measure relates directly to both the magnitude and the direction of the diffusion of water molecules. The favorable performance characteristics of our measure offer the prospect of substantially improving additional post-processing operations that are commonly performed on DTI datasets, such as image segmentation, fiber tracking, noise filtering, and spatial normalization. PMID:18450533

Outer-membrane translocation of bulky small molecules by passive diffusion

PubMed Central

van den Berg, Bert; Prathyusha Bhamidimarri, Satya; Dahyabhai Prajapati, Jigneshkumar; Kleinekathöfer, Ulrich; Winterhalter, Mathias

2015-01-01

The outer membrane (OM) of gram-negative bacteria forms a protective layer around the cell that serves as a permeability barrier to prevent unrestricted access of noxious substances. The permeability barrier of the OM results partly from the limited pore diameters of OM diffusion channels. As a consequence, there is an “OM size-exclusion limit,” and the uptake of bulky molecules with molecular masses of more than ∼600 Da is thought to be mediated by TonB-dependent, active transporters. Intriguingly, the OM protein CymA from Klebsiella oxytoca does not depend on TonB but nevertheless mediates efficient OM passage of cyclodextrins with diameters of up to ∼15 Å. Here we show, by using X-ray crystallography, molecular dynamics simulations, and single-channel electrophysiology, that CymA forms a monomeric 14-stranded β-barrel with a large pore that is occluded on the periplasmic side by the N-terminal 15 residues of the protein. Representing a previously unidentified paradigm in OM transport, CymA mediates the passive diffusion of bulky molecules via an elegant transport mechanism in which a mobile element formed by the N terminus acts as a ligand-expelled gate to preserve the permeability barrier of the OM. PMID:26015567

Development of hydrogel TentaGel shell-core beads for ultrahigh throughput solution-phase screening of encoded OBOC combinatorial small molecule libraries.

PubMed

Baek, Hyoung Gee; Liu, Ruiwu; Lam, Kit S

2009-01-01

The one-bead one-compound (OBOC) combinatorial library method enables the rapid generation and screening of millions of discrete chemical compounds on beads. Most of the OBOC screening methods require the library compounds to remain tethered to the bead during screening process. Methods have also been developed to release library compounds from immobilized beads for in situ solution phase or "lawn" assays. However, this latter approach, while extremely powerful, is severely limited by the lack of suitable solid supports for such assays. Here, we report on the development of a novel hydrogel TentaGel shell-core (HTSC) bead in which hydrogel is grafted onto the polystyrene-based TentaGel (TG) bead as an outer shell (5-80 mum thick) via free radical surface-initiated polymerization. This novel shell-core bilayer resin enables the preparation of encoded OBOC combinatorial small molecule libraries, such that the library compounds reside on the highly hydrophilic outer layer and the coding tags reside in the polystyrene-based TG core. Using fluorescein as a model small molecule compound, we have demonstrated that fluorescein molecules that have been linked covalently to the hydrogel shell via a disulfide bond could readily diffuse out of the hydrogel layer into the bead surrounding after reduction with dithiothreitol. In contrast, under identical condition, the released fluorescein molecules remained bound to unmodified TG bead. We have prepared an encoded OBOC small molecule library on the novel shell-core beads and demonstrated that the beads can be readily decoded.

Remote excitation fluorescence correlation spectroscopy using silver nanowires

NASA Astrophysics Data System (ADS)

Su, Liang; Yuan, Haifeng; Lu, Gang; Hofkens, Johan; Roeffaers, Maarten; Uji-i, Hiroshi

2014-11-01

Fluorescence correlation spectroscopy (FCS), a powerful tool to resolve local properties, dynamical process of molecules, rotational and translational diffusion motions, relies on the fluctuations of florescence observables in the observation volume. In the case of rare transition events or small dynamical fluctuations, FCS requires few molecules or even single molecules in the observation volume at a time to minimize the background signals. Metal nanoparticle which possess unique localized surface plasmon resonance (LSPR) have been used to reduce the observation volume down to sub-diffraction limited scale while maintain at high analyst concentration up to tens of micromolar. Nevertheless, the applications of functionalized nanoparticles in living cell are limited due to the continuous diffusion after cell uptake, which makes it difficult to target the region of interests in the cell. In this work, we demonstrate the use of silver nanowires for remote excitation FCS on fluorescent molecules in solution. By using propagation surface plasmon polaritons (SPPs) which supported by the silver nanowire to excite the fluorescence, both illumination and observation volume can be reduced simultaneously. In such a way, less perturbation is induced to the target region, and this will broaden the application scope of silver nanowire as tip in single cell endoscopy.

Precision platform for convex lens-induced confinement microscopy

NASA Astrophysics Data System (ADS)

Berard, Daniel; McFaul, Christopher M. J.; Leith, Jason S.; Arsenault, Adriel K. J.; Michaud, François; Leslie, Sabrina R.

2013-10-01

We present the conception, fabrication, and demonstration of a versatile, computer-controlled microscopy device which transforms a standard inverted fluorescence microscope into a precision single-molecule imaging station. The device uses the principle of convex lens-induced confinement [S. R. Leslie, A. P. Fields, and A. E. Cohen, Anal. Chem. 82, 6224 (2010)], which employs a tunable imaging chamber to enhance background rejection and extend diffusion-limited observation periods. Using nanopositioning stages, this device achieves repeatable and dynamic control over the geometry of the sample chamber on scales as small as the size of individual molecules, enabling regulation of their configurations and dynamics. Using microfluidics, this device enables serial insertion as well as sample recovery, facilitating temporally controlled, high-throughput measurements of multiple reagents. We report on the simulation and experimental characterization of this tunable chamber geometry, and its influence upon the diffusion and conformations of DNA molecules over extended observation periods. This new microscopy platform has the potential to capture, probe, and influence the configurations of single molecules, with dramatically improved imaging conditions in comparison to existing technologies. These capabilities are of immediate interest to a wide range of research and industry sectors in biotechnology, biophysics, materials, and chemistry.

Entropic trapping of macromolecules by mesoscopic periodic voids in a polymer hydrogel

NASA Astrophysics Data System (ADS)

Liu, Lei; Li, Pusheng; Asher, Sanford A.

1999-01-01

The separation of macromolecules such as polymers and DNA by means of electrophoresis, gel permeation chromatography or filtration exploits size-dependent differences in the time it takes for the molecules to migrate through a random porous network. Transport through the gel matrices, which usually consist of full swollen crosslinked polymers, depends on the relative size of the macromolecule compared with the pore radius. Sufficiently small molecules are thought to adopt an approximately spherical conformation when diffusing through the gel matrix, whereas larger ones are forced to migrate in a snake-like fashion. Molecules of intermediate size, however, can get temporarily trapped in the largest pores of the matrix, where the molecule can extend and thus maximize its conformational entropy. This `entropic trapping' is thought to increase the dependence of diffusion rate on molecular size. Here we report the direct experimental verification of this phenomenon. Bragg diffraction from a hydrogel containing a periodic array of monodisperse water voids confirms that polymers of different weights partition between the hydrogel matrix and the water voids according to the predictions of the entropic trapping theory. Our approach might also lead to the design of improved separation media based on entropic trapping.

A small diffusible signal molecule is responsible for the global control of virulence and exoenzyme production in the plant pathogen Erwinia carotovora.

PubMed Central

Pirhonen, M; Flego, D; Heikinheimo, R; Palva, E T

1993-01-01

Virulence of the plant pathogen Erwinia carotovora subsp. carotovora is dependent on the production and secretion of a complex arsenal of plant cell wall-degrading enzymes. Production of these exoenzymes is controlled by a global regulatory mechanism. A virulent mutants in one of the regulatory loci, expI, show a pleiotropic defect in the growth phase-dependent transcriptional activation of exoenzyme gene expression. The expI gene encodes a 26 kDa polypeptide that is structurally and functionally related to the luxI gene product of Vibrio fischeri. Functional similarity of expI and luxI has been demonstrated by reciprocal genetic complementation experiments. LuxI controls bioluminescence in V.fischeri in a growth phase-dependent manner by directing the synthesis of the diffusible autoinducer, N-(3-oxohexanoyl) homoserine lactone. E.c. subsp. carotovora expI+ strains or Escherichia coli harboring the cloned expI gene excrete a small diffusible signal molecule that complements the expI mutation of Erwinia as well as a luxI mutation of V.fischeri. This extracellular complementation can also be achieved by E.coli harboring the luxI gene from V.fischeri or by adding the synthetic V.fischeri autoinducer. Both the production of the plant tissue-macerating exoenzymes and the ability of the bacteria to propagate in planta are restored in expI mutants by autoinducer addition. These data suggest that the same signal molecule is employed in control of such diverse processes as virulence in a plant pathogen and bioluminescence in a marine bacterium, and may represent a general mechanism by which bacteria modulate gene expression in response to changing environmental conditions. Images PMID:8508772

A small diffusible signal molecule is responsible for the global control of virulence and exoenzyme production in the plant pathogen Erwinia carotovora.

PubMed

Pirhonen, M; Flego, D; Heikinheimo, R; Palva, E T

1993-06-01

Virulence of the plant pathogen Erwinia carotovora subsp. carotovora is dependent on the production and secretion of a complex arsenal of plant cell wall-degrading enzymes. Production of these exoenzymes is controlled by a global regulatory mechanism. A virulent mutants in one of the regulatory loci, expI, show a pleiotropic defect in the growth phase-dependent transcriptional activation of exoenzyme gene expression. The expI gene encodes a 26 kDa polypeptide that is structurally and functionally related to the luxI gene product of Vibrio fischeri. Functional similarity of expI and luxI has been demonstrated by reciprocal genetic complementation experiments. LuxI controls bioluminescence in V.fischeri in a growth phase-dependent manner by directing the synthesis of the diffusible autoinducer, N-(3-oxohexanoyl) homoserine lactone. E.c. subsp. carotovora expI+ strains or Escherichia coli harboring the cloned expI gene excrete a small diffusible signal molecule that complements the expI mutation of Erwinia as well as a luxI mutation of V.fischeri. This extracellular complementation can also be achieved by E.coli harboring the luxI gene from V.fischeri or by adding the synthetic V.fischeri autoinducer. Both the production of the plant tissue-macerating exoenzymes and the ability of the bacteria to propagate in planta are restored in expI mutants by autoinducer addition. These data suggest that the same signal molecule is employed in control of such diverse processes as virulence in a plant pathogen and bioluminescence in a marine bacterium, and may represent a general mechanism by which bacteria modulate gene expression in response to changing environmental conditions.

Quantifying Multistate Cytoplasmic Molecular Diffusion in Bacterial Cells via Inverse Transform of Confined Displacement Distribution.

PubMed

Chen, Tai-Yen; Jung, Won; Santiago, Ace George; Yang, Feng; Krzemiński, Łukasz; Chen, Peng

2015-11-12

Single-molecule tracking (SMT) of fluorescently tagged cytoplasmic proteins can provide valuable information on the underlying biological processes in living cells via subsequent analysis of the displacement distributions; however, the confinement effect originated from the small size of a bacterial cell skews the protein's displacement distribution and complicates the quantification of the intrinsic diffusive behaviors. Using the inverse transformation method, we convert the skewed displacement distribution (for both 2D and 3D imaging conditions) back to that in free space for systems containing one or multiple (non)interconverting Brownian diffusion states, from which we can reliably extract the number of diffusion states as well as their intrinsic diffusion coefficients and respective fractional populations. We further demonstrate a successful application to experimental SMT data of a transcription factor in living E. coli cells. This work allows a direct quantitative connection between cytoplasmic SMT data with diffusion theory for analyzing molecular diffusive behavior in live bacteria.

Rotation and diffusion of naphthalene on Pt(111)

NASA Astrophysics Data System (ADS)

Kolsbjerg, E. L.; Goubert, G.; McBreen, P. H.; Hammer, B.

2018-03-01

The behavior of naphthalene on Pt(111) surfaces is studied by combining insight from scanning tunneling microscopy (STM) and van der Waals enabled density functional theory. Adsorption, diffusion, and rotation are investigated by a series of variable temperature STM experiments revealing naphthalene ability to rotate on-site with ease with a rotational barrier of 0.69 eV. Diffusion to neighbouring sites is found to be more difficult. The experimental results are in good agreement with the theoretical investigations which confirm that the barrier for diffusion is slightly higher than the one for rotation. The theoretical barriers for rotation and translation are found to be 0.75 and 0.78 eV, respectively. An automatic mapping of the possible diffusion pathways reveals very detailed diffusion paths with many small local minima that would have been practically impossible to find manually. This automated procedure provides detailed insight into the preferred diffusion pathways that are important for our understanding of molecule-substrate interactions.

Quantifying Multistate Cytoplasmic Molecular Diffusion in Bacterial Cells via Inverse Transform of Confined Displacement Distribution

PubMed Central

2016-01-01

Single-molecule tracking (SMT) of fluorescently tagged cytoplasmic proteins can provide valuable information on the underlying biological processes in living cells via subsequent analysis of the displacement distributions; however, the confinement effect originated from the small size of a bacterial cell skews the protein’s displacement distribution and complicates the quantification of the intrinsic diffusive behaviors. Using the inverse transformation method, we convert the skewed displacement distribution (for both 2D and 3D imaging conditions) back to that in free space for systems containing one or multiple (non)interconverting Brownian diffusion states, from which we can reliably extract the number of diffusion states as well as their intrinsic diffusion coefficients and respective fractional populations. We further demonstrate a successful application to experimental SMT data of a transcription factor in living E. coli cells. This work allows a direct quantitative connection between cytoplasmic SMT data with diffusion theory for analyzing molecular diffusive behavior in live bacteria. PMID:26491971

Diffusive shunting of gases and other molecules in the renal vasculature: physiological and evolutionary significance.

PubMed

Ngo, Jennifer P; Ow, Connie P C; Gardiner, Bruce S; Kar, Saptarshi; Pearson, James T; Smith, David W; Evans, Roger G

2016-11-01

Countercurrent systems have evolved in a variety of biological systems that allow transfer of heat, gases, and solutes. For example, in the renal medulla, the countercurrent arrangement of vascular and tubular elements facilitates the trapping of urea and other solutes in the inner medulla, which in turn enables the formation of concentrated urine. Arteries and veins in the cortex are also arranged in a countercurrent fashion, as are descending and ascending vasa recta in the medulla. For countercurrent diffusion to occur, barriers to diffusion must be small. This appears to be characteristic of larger vessels in the renal cortex. There must also be gradients in the concentration of molecules between afferent and efferent vessels, with the transport of molecules possible in either direction. Such gradients exist for oxygen in both the cortex and medulla, but there is little evidence that large gradients exist for other molecules such as carbon dioxide, nitric oxide, superoxide, hydrogen sulfide, and ammonia. There is some experimental evidence for arterial-to-venous (AV) oxygen shunting. Mathematical models also provide evidence for oxygen shunting in both the cortex and medulla. However, the quantitative significance of AV oxygen shunting remains a matter of controversy. Thus, whereas the countercurrent arrangement of vasa recta in the medulla appears to have evolved as a consequence of the evolution of Henle's loop, the evolutionary significance of the intimate countercurrent arrangement of blood vessels in the renal cortex remains an enigma. Copyright © 2016 the American Physiological Society.

Discrete Cu(i) complexes for azide-alkyne annulations of small molecules inside mammalian cells.

PubMed

Miguel-Ávila, Joan; Tomás-Gamasa, María; Olmos, Andrea; Pérez, Pedro J; Mascareñas, José L

2018-02-21

The archetype reaction of "click" chemistry, namely, the copper-promoted azide-alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interior of mammalian cells, are essentially unknown. Herein we demonstrate that isolated, well-defined copper(i)-tris(triazolyl) complexes featuring designed ligands can readily enter mammalian cells and promote intracellular CuAAC annulations of small, freely diffusible molecules. In addition to simplifying protocols and avoiding the addition of "non-innocent" reductants, the use of these premade copper complexes leads to more efficient processes than with the alternative, in situ made copper species prepared from Cu(ii) sources, tris(triazole) ligands and sodium ascorbate. Under the reaction conditions, the well-defined copper complexes exhibit very good cell penetration properties, and do not present significant toxicities.

Communication: Coordinate-dependent diffusivity from single molecule trajectories

NASA Astrophysics Data System (ADS)

Berezhkovskii, Alexander M.; Makarov, Dmitrii E.

2017-11-01

Single-molecule observations of biomolecular folding are commonly interpreted using the model of one-dimensional diffusion along a reaction coordinate, with a coordinate-independent diffusion coefficient. Recent analysis, however, suggests that more general models are required to account for single-molecule measurements performed with high temporal resolution. Here, we consider one such generalization: a model where the diffusion coefficient can be an arbitrary function of the reaction coordinate. Assuming Brownian dynamics along this coordinate, we derive an exact expression for the coordinate-dependent diffusivity in terms of the splitting probability within an arbitrarily chosen interval and the mean transition path time between the interval boundaries. This formula can be used to estimate the effective diffusion coefficient along a reaction coordinate directly from single-molecule trajectories.

Photoinduced random molecular reorientation by nonradiative energy relaxation: An experimental test

NASA Astrophysics Data System (ADS)

Manzo, C.; Paparo, D.; Marrucci, L.

2004-11-01

By measuring the time-resolved fluorescence depolarization as a function of light excitation wavelength we address the question of a possible photoinduced orientational randomization of amino-anthraquinone dyes in liquid solutions. We find no significant dependence within the experimental uncertainties of both the initial molecule anisotropy and of the subsequent rotational diffusion dynamics on the photon energy. This indicates that this effect, if present, must be very small. A simple model of photoinduced local heating and corresponding enhanced rotational diffusion is in accordance with this result. This null result rules out some recent proposals that photoinduced local heating may contribute significantly to molecular reorientation effects in different materials. A small but statistically significant effect of photon energy is instead found in the excited-state lifetime of the dye.

Determination of the effective diffusivity of water in a poly (methyl methacrylate) membrane containing carbon nanotubes using kinetic Monte Carlo simulations.

PubMed

Mermigkis, Panagiotis G; Tsalikis, Dimitrios G; Mavrantzas, Vlasis G

2015-10-28

A kinetic Monte Carlo (kMC) simulation algorithm is developed for computing the effective diffusivity of water molecules in a poly(methyl methacrylate) (PMMA) matrix containing carbon nanotubes (CNTs) at several loadings. The simulations are conducted on a cubic lattice to the bonds of which rate constants are assigned governing the elementary jump events of water molecules from one lattice site to another. Lattice sites belonging to PMMA domains of the membrane are assigned different rates than lattice sites belonging to CNT domains. Values of these two rate constants are extracted from available numerical data for water diffusivity within a PMMA matrix and a CNT pre-computed on the basis of independent atomistic molecular dynamics simulations, which show that water diffusivity in CNTs is 3 orders of magnitude faster than in PMMA. Our discrete-space, continuum-time kMC simulation results for several PMMA-CNT nanocomposite membranes (characterized by different values of CNT length L and diameter D and by different loadings of the matrix in CNTs) demonstrate that the overall or effective diffusivity, D(eff), of water in the entire polymeric membrane is of the same order of magnitude as its diffusivity in PMMA domains and increases only linearly with the concentration C (vol. %) in nanotubes. For a constant value of the concentration C, D(eff) is found to vary practically linearly also with the CNT aspect ratio L/D. The kMC data allow us to propose a simple bilinear expression for D(eff) as a function of C and L/D that can describe the numerical data for water mobility in the membrane extremely accurately. Additional simulations with two different CNT configurations (completely random versus aligned) show that CNT orientation in the polymeric matrix has only a minor effect on D(eff) (as long as CNTs do not fully penetrate the membrane). We have also extensively analyzed and quantified sublinear (anomalous) diffusive phenomena over small to moderate times and correlated them with the time needed for penetrant water molecules to explore the available large, fast-diffusing CNT pores before Fickian diffusion is reached.

Determination of the effective diffusivity of water in a poly (methyl methacrylate) membrane containing carbon nanotubes using kinetic Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Mermigkis, Panagiotis G.; Tsalikis, Dimitrios G.; Mavrantzas, Vlasis G.

2015-10-01

A kinetic Monte Carlo (kMC) simulation algorithm is developed for computing the effective diffusivity of water molecules in a poly(methyl methacrylate) (PMMA) matrix containing carbon nanotubes (CNTs) at several loadings. The simulations are conducted on a cubic lattice to the bonds of which rate constants are assigned governing the elementary jump events of water molecules from one lattice site to another. Lattice sites belonging to PMMA domains of the membrane are assigned different rates than lattice sites belonging to CNT domains. Values of these two rate constants are extracted from available numerical data for water diffusivity within a PMMA matrix and a CNT pre-computed on the basis of independent atomistic molecular dynamics simulations, which show that water diffusivity in CNTs is 3 orders of magnitude faster than in PMMA. Our discrete-space, continuum-time kMC simulation results for several PMMA-CNT nanocomposite membranes (characterized by different values of CNT length L and diameter D and by different loadings of the matrix in CNTs) demonstrate that the overall or effective diffusivity, Deff, of water in the entire polymeric membrane is of the same order of magnitude as its diffusivity in PMMA domains and increases only linearly with the concentration C (vol. %) in nanotubes. For a constant value of the concentration C, Deff is found to vary practically linearly also with the CNT aspect ratio L/D. The kMC data allow us to propose a simple bilinear expression for Deff as a function of C and L/D that can describe the numerical data for water mobility in the membrane extremely accurately. Additional simulations with two different CNT configurations (completely random versus aligned) show that CNT orientation in the polymeric matrix has only a minor effect on Deff (as long as CNTs do not fully penetrate the membrane). We have also extensively analyzed and quantified sublinear (anomalous) diffusive phenomena over small to moderate times and correlated them with the time needed for penetrant water molecules to explore the available large, fast-diffusing CNT pores before Fickian diffusion is reached.

One and two hydrogen molecules in the large cage of the structure II clathrate hydrate: quantum translation-rotation dynamics close to the cage wall.

PubMed

Sebastianelli, Francesco; Xu, Minzhong; Kanan, Dalal K; Bacić, Zlatko

2007-07-19

We have performed a rigorous theoretical study of the quantum translation-rotation (T-R) dynamics of one and two H2 and D2 molecules confined inside the large hexakaidecahedral (5(12)6(4)) cage of the sII clathrate hydrate. For a single encapsulated H2 and D2 molecule, accurate quantum five-dimensional calculations of the T-R energy levels and wave functions are performed that include explicitly, as fully coupled, all three translational and the two rotational degrees of freedom of the hydrogen molecule, while the cage is taken to be rigid. In addition, the ground-state properties, energetics, and spatial distribution of one and two p-H2 and o-D2 molecules in the large cage are calculated rigorously using the diffusion Monte Carlo method. These calculations reveal that the low-energy T-R dynamics of hydrogen molecules in the large cage are qualitatively different from that inside the small cage, studied by us recently. This is caused by the following: (i) The large cage has a cavity whose diameter is about twice that of the small cage for the hydrogen molecule. (ii) In the small cage, the potential energy surface (PES) for H2 is essentially flat in the central region, while in the large cage the PES has a prominent maximum at the cage center, whose height exceeds the T-R zero-point energy of H2/D2. As a result, the guest molecule is excluded from the central part of the large cage, its wave function localized around the off-center global minimum. Peculiar quantum dynamics of the hydrogen molecule squeezed between the central maximum and the cage wall manifests in the excited T-R states whose energies and wave functions differ greatly from those for the small cage. Moreover, they are sensitive to the variations in the hydrogen-bonding topology, which modulate the corrugation of the cage wall.

CO2 diffusion in champagne wines: a molecular dynamics study.

PubMed

Perret, Alexandre; Bonhommeau, David A; Liger-Belair, Gérard; Cours, Thibaud; Alijah, Alexander

2014-02-20

Although diffusion is considered as the main physical process responsible for the nucleation and growth of carbon dioxide bubbles in sparkling beverages, the role of each type of molecule in the diffusion process remains unclear. In the present study, we have used the TIP5P and SPC/E water models to perform force field molecular dynamics simulations of CO2 molecules in water and in a water/ethanol mixture respecting Champagne wine proportions. CO2 diffusion coefficients were computed by applying the generalized Fick's law for the determination of multicomponent diffusion coefficients, a law that simplifies to the standard Fick's law in the case of champagnes. The CO2 diffusion coefficients obtained in pure water and water/ethanol mixtures composed of TIP5P water molecules were always found to exceed the coefficients obtained in mixtures composed of SPC/E water molecules, a trend that was attributed to a larger propensity of SPC/E water molecules to form hydrogen bonds. Despite the fact that the SPC/E model is more accurate than the TIP5P model to compute water self-diffusion and CO2 diffusion in pure water, the diffusion coefficients of CO2 molecules in the water/ethanol mixture are in much better agreement with the experimental values of 1.4 - 1.5 × 10(-9) m(2)/s obtained for Champagne wines when the TIP5P model is employed. This difference was deemed to rely on the larger propensity of SPC/E water molecules to maintain the hydrogen-bonded network between water molecules and form new hydrogen bonds with ethanol, although statistical issues cannot be completely excluded. The remarkable agreement between the theoretical CO2 diffusion coefficients obtained within the TIP5P water/ethanol mixture and the experimental data specific to Champagne wines makes us infer that the diffusion coefficient in these emblematic hydroalcoholic sparkling beverages is expected to remain roughly constant whathever their proportions in sugars, glycerol, or peptides.

A hybrid continuous-discrete method for stochastic reaction-diffusion processes.

PubMed

Lo, Wing-Cheong; Zheng, Likun; Nie, Qing

2016-09-01

Stochastic fluctuations in reaction-diffusion processes often have substantial effect on spatial and temporal dynamics of signal transductions in complex biological systems. One popular approach for simulating these processes is to divide the system into small spatial compartments assuming that molecules react only within the same compartment and jump between adjacent compartments driven by the diffusion. While the approach is convenient in terms of its implementation, its computational cost may become prohibitive when diffusive jumps occur significantly more frequently than reactions, as in the case of rapid diffusion. Here, we present a hybrid continuous-discrete method in which diffusion is simulated using continuous approximation while reactions are based on the Gillespie algorithm. Specifically, the diffusive jumps are approximated as continuous Gaussian random vectors with time-dependent means and covariances, allowing use of a large time step, even for rapid diffusion. By considering the correlation among diffusive jumps, the approximation is accurate for the second moment of the diffusion process. In addition, a criterion is obtained for identifying the region in which such diffusion approximation is required to enable adaptive calculations for better accuracy. Applications to a linear diffusion system and two nonlinear systems of morphogens demonstrate the effectiveness and benefits of the new hybrid method.

Construction of nanostructures for selective lithium ion conduction using self-assembled molecular arrays in supramolecular solids

NASA Astrophysics Data System (ADS)

Moriya, Makoto

2017-12-01

In the development of innovative molecule-based materials, the identification of the structural features in supramolecular solids and the understanding of the correlation between structure and function are important factors. The author investigated the development of supramolecular solid electrolytes by constructing ion conduction paths using a supramolecular hierarchical structure in molecular crystals because the ion conduction path is an attractive key structure due to its ability to generate solid-state ion diffusivity. The obtained molecular crystals exhibited selective lithium ion diffusion via conduction paths consisting of lithium bis(trifluoromethanesulfonyl)amide (LiTFSA) and small molecules such as ether or amine compounds. In the present review, the correlation between the crystal structure and ion conductivity of the obtained molecular crystals is addressed based on the systematic structural control of the ionic conduction paths through the modification of the component molecules. The relationship between the crystal structure and ion conductivity of the molecular crystals provides a guideline for the development of solid electrolytes based on supramolecular solids exhibiting rapid and selective lithium ion conduction.

Fluorescence-correlation spectroscopy study of molecular transport within reversed-phase chromatographic particles compared to planar model surfaces.

PubMed

Cooper, Justin; Harris, Joel M

2014-12-02

Reversed-phase liquid chromatography (RPLC) is a widely used technique for molecular separations. Stationary-phase materials for RPLC generally consist of porous silica-gel particles functionalized with n-alkane ligands. Understanding motions of molecules within the interior of these particles is important for developing efficient chromatographic materials and separations. To characterize these dynamics, time-resolved spectroscopic methods (photobleach recovery, fluorescence correlation, single-molecule imaging) have been adapted to measure molecular diffusion rates, typically at n-alkane-modified planar silica surfaces, which serve as models of chromatographic interfaces. A question arising from these studies is how dynamics of molecules on a planar surface relate to motions of molecules within the interior of a porous chromatographic particle. In this paper, imaging-fluorescence-correlation spectroscopy is used to measure diffusion rates of a fluorescent probe molecule 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) within authentic RPLC porous silica particles and compared with its diffusion at a planar C18-modified surface. The results show that surface diffusion on the planar C18 substrate is much faster than the diffusion rate of the probe molecule through a chromatographic particle. Surface diffusion within porous particles, however, is governed by molecular trajectories along the tortuous contours of the interior surface of the particles. By accounting for the greater surface area that a molecule must explore to diffuse macroscopic distances through the particle, the molecular-scale diffusion rates on the two surfaces can be compared, and they are virtually identical. These results provide support for the relevance of surface-diffusion measurements made on planar model surfaces to the dynamic behavior of molecules on the internal surfaces of porous chromatographic particles.

Surface diffusion of CO on silica-supported Ru particles: 13C nuclear magnetic resonance studies

NASA Astrophysics Data System (ADS)

Duncan, T. M.; Thayer, A. M.; Root, T. W.

1990-02-01

Portions of CO adsorbed on Ru particles, selected by the orientation of the C-O bond relative to an external magnetic field, are labeled by inversion of the 13C nuclear magnetic dipole. Changes in the orientation of the CO bond of these labeled molecules are then observed with 13C NMR spectroscopy. The temperature dependence and rate of reorientation are consistent with surface diffusion on Ru particles with small numbers of flat faces. The insensitivity to CO pressure in the range 0.5-100 Torr discounts stimulated desorption by gas-phase CO.

Adsorption of gas molecules on Cu impurities embedded monolayer MoS2: A first- principles study

NASA Astrophysics Data System (ADS)

Zhao, B.; Li, C. Y.; Liu, L. L.; Zhou, B.; Zhang, Q. K.; Chen, Z. Q.; Tang, Z.

2016-09-01

Adsorption of small gas molecules (O2, NO, NO2 and NH3) on transition-metal Cu atom embedded monolayer MoS2 was investigated by first-principles calculations based on the density-functional theory (DFT). The embedded Cu atom is strongly constrained on the sulfur vacancy of monolayer MoS2 with a high diffusion barrier. The stable adsorption geometry, charge transfer and electronic structures of these gas molecules on monolayer MoS2 embedded with transition-metal Cu atom are discussed in detail. It is found that the monolayer MoS2 with embedded Cu atom can effectively capture these gas molecules with high adsorption energy. The NH3 molecule acts as electron donor after adsorption, which is different from the other gas molecules (O2, NO, and NO2). The results suggest that MoS2-Cu system may be promising for future applications in gas molecules sensing and catalysis, which is similar to those of the transition-metal embedded graphene.

Inferring diffusion in single live cells at the single-molecule level

PubMed Central

Robson, Alex; Burrage, Kevin; Leake, Mark C.

2013-01-01

The movement of molecules inside living cells is a fundamental feature of biological processes. The ability to both observe and analyse the details of molecular diffusion in vivo at the single-molecule and single-cell level can add significant insight into understanding molecular architectures of diffusing molecules and the nanoscale environment in which the molecules diffuse. The tool of choice for monitoring dynamic molecular localization in live cells is fluorescence microscopy, especially so combining total internal reflection fluorescence with the use of fluorescent protein (FP) reporters in offering exceptional imaging contrast for dynamic processes in the cell membrane under relatively physiological conditions compared with competing single-molecule techniques. There exist several different complex modes of diffusion, and discriminating these from each other is challenging at the molecular level owing to underlying stochastic behaviour. Analysis is traditionally performed using mean square displacements of tracked particles; however, this generally requires more data points than is typical for single FP tracks owing to photophysical instability. Presented here is a novel approach allowing robust Bayesian ranking of diffusion processes to discriminate multiple complex modes probabilistically. It is a computational approach that biologists can use to understand single-molecule features in live cells. PMID:23267182

Determination of Molecular Self-Diffusion Coefficients Using Pulsed-Field-Gradient NMR: An Experiment for Undergraduate Physical Chemistry Laboratory

ERIC Educational Resources Information Center

Harmon, Jennifer; Coffman, Cierra; Villarrial, Spring; Chabolla, Steven; Heisel, Kurt A.; Krishnan, Viswanathan V.

2012-01-01

NMR spectroscopy has become one of the primary tools that chemists utilize to characterize a range of chemical species in the solution phase, from small organic molecules to medium-sized proteins. A discussion of NMR spectroscopy is an essential component of physical and biophysical chemistry lecture courses, and a number of instructional…

Stochastic algorithm for simulating gas transport coefficients

NASA Astrophysics Data System (ADS)

Rudyak, V. Ya.; Lezhnev, E. V.

2018-02-01

The aim of this paper is to create a molecular algorithm for modeling the transport processes in gases that will be more efficient than molecular dynamics method. To this end, the dynamics of molecules are modeled stochastically. In a rarefied gas, it is sufficient to consider the evolution of molecules only in the velocity space, whereas for a dense gas it is necessary to model the dynamics of molecules also in the physical space. Adequate integral characteristics of the studied system are obtained by averaging over a sufficiently large number of independent phase trajectories. The efficiency of the proposed algorithm was demonstrated by modeling the coefficients of self-diffusion and the viscosity of several gases. It was shown that the accuracy comparable to the experimental one can be obtained on a relatively small number of molecules. The modeling accuracy increases with the growth of used number of molecules and phase trajectories.

Fluctuation correlation models for receptor immobilization

NASA Astrophysics Data System (ADS)

Fourcade, B.

2017-12-01

Nanoscale dynamics with cycles of receptor diffusion and immobilization by cell-external-or-internal factors is a key process in living cell adhesion phenomena at the origin of a plethora of signal transduction pathways. Motivated by modern correlation microscopy approaches, the receptor correlation functions in physical models based on diffusion-influenced reaction is studied. Using analytical and stochastic modeling, this paper focuses on the hybrid regime where diffusion and reaction are not truly separable. The time receptor autocorrelation functions are shown to be indexed by different time scales and their asymptotic expansions are given. Stochastic simulations show that this analysis can be extended to situations with a small number of molecules. It is also demonstrated that this analysis applies when receptor immobilization is coupled to environmental noise.

Monitoring and Manipulating Motions of Single Molecules/Nanoparticles

NASA Astrophysics Data System (ADS)

Chen, Fang

This dissertation has two main research components: 1. the study of mass transport in confined environments; 2. the effort toward driving a molecular car on a solid surface. Understanding mass transport processes, e.g., diffusion, migration, and adsorption/desorption in confined space is important not only to fundamental sciences but also to advanced applications. So far, they are poorly understood because of technical challenges: insufficient spatial and/or temporal resolutions. In this dissertation, we made efforts toward understanding molecular/particular dynamics in confined space by combining a recently developed super resolution technique, stimulated depletion emission microscopy (STED), with the high temporal resolution technique, fluorescence correlation spectroscopy (FCS). We first explored the feasibility of using conventional FCS to study diffusion in a model confined space: cylindrical pores. Since there is no analytical solution to solve the autocorrelation function (ACF) in confined space, we simulated single particle diffusion in hundred-nanometer pores using Monte Carlo simulation. We found that confined 2D diffusion and unconfined 1D diffusion dynamics are separated in both intensity traces and autocorrelation functions, which gives a new opportunity to extract the axial diffusion coefficient in cylindrical pores. We then experimentally studied 45 nm particles diffusing in 300 nm alumina pores. The acquired axial diffusion coefficient is consistent with the expected value. Conventional confocal FCS is insufficient to resolve lateral diffusion in confined space because of the diffraction limit in spatial resolution. To pave the way of using STED microscopy to study the anisotropic diffusion in confined space, we theoretically investigated STED-FCS in cylindrical pores. It showed that by reducing the spatial resolution from 250 nm to 50 nm in STED microscopy, we would be able to determine both lateral and axial diffusion coefficients in hundred-nanometer pores in theory. We then experimentally studied nanoparticles diffusing on membrane filters containing 200 nm polyethyleneglycol- or C18-modified pores. Using STED microscopy, we resolved for the first time how small particles are retained by the pores. Trapping by the pore entrances rather than adsorption is responsible for the retention. Further studies on C18-modified pores showed consistency in Gibbs free energy about the retention process. In addition, in order to understand how nanoparticles interact with the surface when they are forced to be on, or very close to, the surface, we studied nanosecond rotation dynamics of gold nanorods with one end attached on the surface. We found that the nanorod motion is dominated by van der Waals interaction-induced immobilization rather Brownian rotational diffusion as previously thought. The actual rotation, during which the nanorod transits from one immobilized state to the other, slows down by 50 times. The second part of the research is the collaboration with Tour's group in Rice University. The ultimate goal is to use light to drive a motorized nanocar at ambient conditions. To fulfill this goal, we first studied the moving kinetics of adamantane-wheeled nanocars on hydroxylated and PEG-modified surfaces using single molecule fluorescence microscopy. We found that nanocars' diffusion slows down on solid surface over time, which is possibly caused by the increased hydrophobicity of the substrate surface due to the adsorbates from the air. A sticky-spots model was proposed to explain the observed slowing down. To find out whether a light-activatable motor works when it is incorporated into a nanocar, we carefully designed a series of molecules containing a regular motor, a slow motor, a nonunidirectional motor, and no motor. We found that a fast unidirectional rotating motor enhanced the diffusion of the molecule in solution upon UV-illumination. Detailed analysis suggested that the unimolecular submersible nanomachine (USN) will give 9-nm step upon each motor actuation. This is the first nanomachine that gives mechanical motion at small molecular scale.

Reduction of diffusional defocusing in hydrodynamically focused flows

DOEpatents

Affleck, Rhett L.; Demas, James N.; Goodwin, Peter M.; Keller, Richard; Wu, Ming

1998-01-01

An analyte fluid stream with first molecules having relatively low molecular weight and a corresponding high coefficient of diffusion has reduced diffusional defocusing out of an analyte fluid stream. The analyte fluid stream of first molecules is associated with second molecules of relatively high molecular weight having a relatively low coefficient of diffusion and a binding constant effective to associate with the first molecules. A focused analyte fluid stream is maintained since the combined molecular weight of the associated first and second molecules is effective to minimize diffusion of the first molecules out of the analyte fluid stream.

Reduction of diffusional defocusing in hydrodynamically focused flows

DOEpatents

Affleck, R.L.; Demas, J.N.; Goodwin, P.M.; Keller, R.; Wu, M.

1998-09-01

An analyte fluid stream with first molecules having relatively low molecular weight and a corresponding high coefficient of diffusion has reduced diffusional defocusing out of an analyte fluid stream. The analyte fluid stream of first molecules is associated with second molecules of relatively high molecular weight having a relatively low coefficient of diffusion and a binding constant effective to associate with the first molecules. A focused analyte fluid stream is maintained since the combined molecular weight of the associated first and second molecules is effective to minimize diffusion of the first molecules out of the analyte fluid stream. 6 figs.

Multiscale Modeling of Diffusion in a Crowded Environment.

PubMed

Meinecke, Lina

2017-11-01

We present a multiscale approach to model diffusion in a crowded environment and its effect on the reaction rates. Diffusion in biological systems is often modeled by a discrete space jump process in order to capture the inherent noise of biological systems, which becomes important in the low copy number regime. To model diffusion in the crowded cell environment efficiently, we compute the jump rates in this mesoscopic model from local first exit times, which account for the microscopic positions of the crowding molecules, while the diffusing molecules jump on a coarser Cartesian grid. We then extract a macroscopic description from the resulting jump rates, where the excluded volume effect is modeled by a diffusion equation with space-dependent diffusion coefficient. The crowding molecules can be of arbitrary shape and size, and numerical experiments demonstrate that those factors together with the size of the diffusing molecule play a crucial role on the magnitude of the decrease in diffusive motion. When correcting the reaction rates for the altered diffusion we can show that molecular crowding either enhances or inhibits chemical reactions depending on local fluctuations of the obstacle density.

Diffusion in Brain Extracellular Space

PubMed Central

Syková, Eva; Nicholson, Charles

2009-01-01

Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecules in the brain. Deviations from the equation reveal loss of molecules across the blood-brain barrier, through cellular uptake, binding or other mechanisms. Early diffusion measurements used radiolabeled sucrose and other tracers. Presently, the real-time iontophoresis (RTI) method is employed for small ions and the integrative optical imaging (IOI) method for fluorescent macromolecules, including dextrans or proteins. Theoretical models and simulations of the ECS have explored the influence of ECS geometry, effects of dead-space microdomains, extracellular matrix and interaction of macromolecules with ECS channels. Extensive experimental studies with the RTI method employing the cation tetramethylammonium (TMA) in normal brain tissue show that the volume fraction of the ECS typically is about 20% and the tortuosity about 1.6 (i.e. free diffusion coefficient of TMA is reduced by 2.6), although there are regional variations. These parameters change during development and aging. Diffusion properties have been characterized in several interventions, including brain stimulation, osmotic challenge and knockout of extracellular matrix components. Measurements have also been made during ischemia, in models of Alzheimer's and Parkinson's diseases and in human gliomas. Overall, these studies improve our conception of ECS structure and the roles of glia and extracellular matrix in modulating the ECS microenvironment. Knowledge of ECS diffusion properties are valuable in contexts ranging from understanding extrasynaptic volume transmission to the development of paradigms for drug delivery to the brain. PMID:18923183

The Effect of a Fluorophore Photo-Physics on the Lipid Vesicle Diffusion Coefficient Studied by Fluorescence Correlation Spectroscopy.

PubMed

Drabik, Dominik; Przybyło, Magda; Sikorski, Aleksander; Langner, Marek

2016-03-01

Fluorescence Correlation Spectroscopy (FCS) is a technique, which allows determination of the diffusion coefficient and concentration of fluorescent objects suspended in the solution. The measured parameter is the fluctuation of the fluorescence signal emitted by diffusing molecules. When 100 nm DOPC vesicles labeled with various fluorescent dyes (Fluorescein-PE, NBD-PE, Atto488 DOPE or βBodipy FL) were measured, different values of diffusion coefficients have been obtained. These diffusion coefficients were different from the expected values measured using the dynamic light scattering method (DLS). The FCS was initially developed for solutions containing small fluorescent molecules therefore the observed inconsistency may result from the nature of vesicle suspension itself. The duration of the fluorescence signal may depend on the following factors: the exposure time of the labeled object to the excitation beam, the photo-physical properties (e.g., stability) of a fluorophore, the theoretical model used for the calculations of the diffusion coefficient and optical properties of the vesicle suspension. The diffusion coefficients determined for differently labeled liposomes show that its dependence on vesicle size and quantity of fluorescent probed used for labeling was significant demonstrating that the fluorescence properties of the fluorophore itself (bleaching and/or blinking) were critical factors for a correct outcome of FCS experiment. The new, based on combined FCS and DLS measurements, method for the determination of the focal volume prove itself to be useful for the evaluation of a fluorescence dye with respect to its applicability for FCS experiment.

Counting polymers moving through a single ion channel

NASA Astrophysics Data System (ADS)

Bezrukov, Sergey M.; Vodyanoy, Igor; Parsegian, V. Adrian

1994-07-01

THE change in conductance of a small electrolyte-filled capillary owing to the passage of sub-micrometre-sized particles has long been used for particle counting and sizing. A commercial device for such measurements, the Coulter counter, is able to detect particles of sizes down to several tenths of a micrometre1-3. Nuclepore technology (in which pores are etched particle tracks) has extended the lower limit of size detection to 60-nm particles by using a capillary of diameter 0.45 μm (ref. 4). Here we show that natural channel-forming peptides incorporated into a bilayer lipid membrane can be used to detect the passage of single molecules with gyration radii as small as 5-15 Å. From our experiments with alamethicin pores we infer both the average number and the diffusion coefficients of poly(ethylene glycol) molecules in the pore. Our approach provides a means of observing the statistics and mechanics of flexible polymers moving within the confines of precisely defined single-molecule structures.

Towards a minimal stochastic model for a large class of diffusion-reactions on biological membranes.

PubMed

Chevalier, Michael W; El-Samad, Hana

2012-08-28

Diffusion of biological molecules on 2D biological membranes can play an important role in the behavior of stochastic biochemical reaction systems. Yet, we still lack a fundamental understanding of circumstances where explicit accounting of the diffusion and spatial coordinates of molecules is necessary. In this work, we illustrate how time-dependent, non-exponential reaction probabilities naturally arise when explicitly accounting for the diffusion of molecules. We use the analytical expression of these probabilities to derive a novel algorithm which, while ignoring the exact position of the molecules, can still accurately capture diffusion effects. We investigate the regions of validity of the algorithm and show that for most parameter regimes, it constitutes an accurate framework for studying these systems. We also document scenarios where large spatial fluctuation effects mandate explicit consideration of all the molecules and their positions. Taken together, our results derive a fundamental understanding of the role of diffusion and spatial fluctuations in these systems. Simultaneously, they provide a general computational methodology for analyzing a broad class of biological networks whose behavior is influenced by diffusion on membranes.

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

Lv, Chao; Aitchison, Erick W.; Wu, Dongsheng

Hydrogen sulfide (H 2S), a commonly known toxic gas compound, possesses unique chemical features that allow this small solute molecule to quickly diffuse through cell membranes. Taking advantage of the recent orthogonal space tempering (OST) method, we comparatively mapped the transmembrane free energy landscapes of H 2S and its structural analogue, water (H 2O), seeking to decipher the molecular determinants that govern their drastically different permeabilities. Here, as revealed by our OST sampling results, in contrast to the highly polar water solute, hydrogen sulfide is evidently amphipathic, and thus inside membrane is favorably localized at the interfacial region, that is,more » the interface between the polar head-group and nonpolar acyl chain regions. Because the membrane binding affinity of H 2S is mainly governed by its small hydrophobic moiety and the barrier height inbetween the interfacial region and the membrane center is largely determined by its moderate polarity, the transmembrane free energy barriers to encounter by this toxic molecule are very small. Moreover when H2S diffuses from the bulk solution to the membrane center, the above two effects nearly cancel each other, so as to lead to a negligible free energy difference. Lastly, this study not only explains why H 2S can quickly pass through cell membranes but also provides a practical illustration on how to use the OST free energy sampling method to conveniently analyze complex molecular processes.« less

Time scale of diffusion in molecular and cellular biology

NASA Astrophysics Data System (ADS)

Holcman, D.; Schuss, Z.

2014-05-01

Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

Tin-phthalocyanine adsorption and diffusion on Cu and Au (111) surfaces: A density functional theory study

NASA Astrophysics Data System (ADS)

Qin, Dan; Ge, Xu-Jin; Lü, Jing-Tao

2018-05-01

Through density functional theory based calculations, we study the adsorption and diffusion of tin phthalocyanine (SnPc) molecule on Au(111) and Cu(111) surfaces. SnPc has two conformers with Sn pointing to the vacuum (Sn-up) and substrate (Sn-down), respectively. The binding energies of the two conformers with different adsorption sites on the two surfaces, including top, bridge, fcc, hcp, are calculated and compared. It is found that the SnPc molecule binds stronger on Cu(111) surface, with binding energy about 1 eV larger than that on Au(111). Only the bridge and top adsorption sites are stable on Cu(111), while all the four adsorption sites are stable on Au(111), with small diffusion barriers between them. Moreover, the flipping barrier from Sn-up to Sn-down conformer is of the same magnitude on the two metal surfaces. These results are consistent with a recent experiment [Zhang, et al., Angew. Chem., 56, 11769 (2017)], which shows that conformation change from Sn-up to Sn-down on Cu(111) surface can be induced by a C60-functionalized STM tip, while similar change is difficult to realize on Au(111), due to smaller diffusion barrier on Au(111).

A systems approach for tumor pharmacokinetics.

PubMed

Thurber, Greg Michael; Weissleder, Ralph

2011-01-01

Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction of a myriad of new differently sized agents into the clinic. The differences in small and large molecule delivery are becoming increasingly important in combination therapies as well as the use of drugs that modify the physiology of tumors such as anti-angiogenic treatment. The complexity of targeting has led to the development of mathematical models to facilitate understanding, but unfortunately, these studies are often only applicable to a particular molecule, making pharmacokinetic comparisons difficult. Here we develop and describe a framework for categorizing primary pharmacokinetics of drugs in tumors. For modeling purposes, we define drugs not by their mechanism of action but rather their rate-limiting step of delivery. Our simulations account for variations in perfusion, vascularization, interstitial transport, and non-linear local binding and metabolism. Based on a comparison of the fundamental rates determining uptake, drugs were classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism. Simulations comparing small molecule versus macromolecular drugs show a sharp difference in distribution, which has implications for multi-drug therapies. The tissue-level distribution differs widely in tumors for small molecules versus macromolecular biologic drugs, and this should be considered in the design of agents and treatments. An example using antibodies in mouse xenografts illustrates the different in vivo behavior. This type of transport analysis can be used to aid in model development, experimental data analysis, and imaging and therapeutic agent design.

Diffusion of biomass pyrolysis products in H-ZSM-5 by molecular dynamics simulations

DOE PAGES

Bu, Lintao; Nimlos, Mark R.; Robichaud, David J.; ...

2016-12-13

Diffusion of biomass pyrolysis vapors and their upgraded products is an essential catalytic property of zeolites during catalytic fast pyrolysis and likely plays a critical role in the selectivity of these catalysts. Characterizing the diffusivities of representative biofuel molecules is critical to understand shape selectivity and interpret product distribution. Yet, experimental measurements on the diffusivities of oxygenated biofuel molecules at pyrolysis temperatures are very limited in the literature. As an alternative approach, we conducted MD simulations to measure the diffusion coefficients of several selected molecules that are representative of biomass pyrolysis vapors, namely water, methanol, glycolaldehyde, and toluene in H-ZSM-5more » zeolite. The results show the diffusion coefficients calculated via MD simulations are consistent with available NMR measurements at room temperature. The effect of molecular weight and molecular critical diameter on the diffusivity among the chosen model compounds is also examined. Furthermore, we have characterized the diffusivities of representative biofuel molecules, namely xylene isomers, in H-ZSM-5. Our calculations determined that the ratio of the diffusion coefficients for xylene isomers is p-xylene: o-xylene: m-xylene ≈ 83:3:1 at 700 K. Furthermore, our results also demonstrate the different diffusivity between p-xylene and toluene is due to the molecular orientations when the molecules diffuse along the channels in H-ZSM-5 and provide deep insight into the effect of molecular orientation on its diffusivity.« less

γ-Heptalactone is an endogenously produced quorum-sensing molecule regulating growth and secondary metabolite production by Aspergillus nidulans.

PubMed

Williams, Headley E; Steele, Jonathan C P; Clements, Mark O; Keshavarz, Tajalli

2012-11-01

Microbes monitor their population density through a mechanism termed quorum sensing. It is believed that quorum-sensing molecules diffuse from the microbial cells and circulate in the surrounding environment as a function of cell density. When these molecules reach a threshold concentration, the gene expression of the entire population is altered in a coordinated manner. This work provides evidence that Aspergillus nidulans produces at least one small diffusible molecule during its growth cycle which accumulates at high cell density and alters the organism's behaviour. When added to low-density cell cultures, ethyl acetate extracts from stationary phase culture supernatants of A. nidulans resulted in the abolition of the lag phase, induced an earlier deceleration phase with 16.3 % decrease in the final cell dry weight and resulted in a 37.8 % increase in the expression of ipnA::lacZ reporter gene construct, which was used as a marker for penicillin production compared to non-treated controls. The bioactive molecule present in the stationary phase extract was purified to homogeneity and was identified by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy to be γ-heptalactone. This study provides the first evidence that A. nidulans produces γ-heptalactone at a high cell density and it can alter the organism's behaviour at a low cell density. γ-Heptalactone hence acts as a quorum-sensing molecule in the producing strain.

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

Mermigkis, Panagiotis G.; Tsalikis, Dimitrios G.; Institute of Chemical Engineering and High Temperature Chemical Processes, GR 26500 Patras

A kinetic Monte Carlo (kMC) simulation algorithm is developed for computing the effective diffusivity of water molecules in a poly(methyl methacrylate) (PMMA) matrix containing carbon nanotubes (CNTs) at several loadings. The simulations are conducted on a cubic lattice to the bonds of which rate constants are assigned governing the elementary jump events of water molecules from one lattice site to another. Lattice sites belonging to PMMA domains of the membrane are assigned different rates than lattice sites belonging to CNT domains. Values of these two rate constants are extracted from available numerical data for water diffusivity within a PMMA matrixmore » and a CNT pre-computed on the basis of independent atomistic molecular dynamics simulations, which show that water diffusivity in CNTs is 3 orders of magnitude faster than in PMMA. Our discrete-space, continuum-time kMC simulation results for several PMMA-CNT nanocomposite membranes (characterized by different values of CNT length L and diameter D and by different loadings of the matrix in CNTs) demonstrate that the overall or effective diffusivity, D{sub eff}, of water in the entire polymeric membrane is of the same order of magnitude as its diffusivity in PMMA domains and increases only linearly with the concentration C (vol. %) in nanotubes. For a constant value of the concentration C, D{sub eff} is found to vary practically linearly also with the CNT aspect ratio L/D. The kMC data allow us to propose a simple bilinear expression for D{sub eff} as a function of C and L/D that can describe the numerical data for water mobility in the membrane extremely accurately. Additional simulations with two different CNT configurations (completely random versus aligned) show that CNT orientation in the polymeric matrix has only a minor effect on D{sub eff} (as long as CNTs do not fully penetrate the membrane). We have also extensively analyzed and quantified sublinear (anomalous) diffusive phenomena over small to moderate times and correlated them with the time needed for penetrant water molecules to explore the available large, fast-diffusing CNT pores before Fickian diffusion is reached.« less

Brain Extracellular Space: The Final Frontier of Neuroscience.

PubMed

Nicholson, Charles; Hrabětová, Sabina

2017-11-21

Brain extracellular space is the narrow microenvironment that surrounds every cell of the central nervous system. It contains a solution that closely resembles cerebrospinal fluid with the addition of extracellular matrix molecules. The space provides a reservoir for ions essential to the electrical activity of neurons and forms an intercellular chemical communication channel. Attempts to reveal the size and structure of the extracellular space using electron microscopy have had limited success; however, a biophysical approach based on diffusion of selected probe molecules has proved useful. A point-source paradigm, realized in the real-time iontophoresis method using tetramethylammonium, as well as earlier radiotracer methods, have shown that the extracellular space occupies ∼20% of brain tissue and small molecules have an effective diffusion coefficient that is two-fifths that in a free solution. Monte Carlo modeling indicates that geometrical constraints, including dead-space microdomains, contribute to the hindrance to diffusion. Imaging the spread of macromolecules shows them increasingly hindered as a function of size and suggests that the gaps between cells are predominantly ∼40 nm with wider local expansions that may represent dead-spaces. Diffusion measurements also characterize interactions of ions and proteins with the chondroitin and heparan sulfate components of the extracellular matrix; however, the many roles of the matrix are only starting to become apparent. The existence and magnitude of bulk flow and the so-called glymphatic system are topics of current interest and controversy. The extracellular space is an exciting area for research that will be propelled by emerging technologies. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Unifying diffusion and seepage for nonlinear gas transport in multiscale porous media

NASA Astrophysics Data System (ADS)

Song, Hongqing; Wang, Yuhe; Wang, Jiulong; Li, Zhengyi

2016-09-01

We unify the diffusion and seepage process for nonlinear gas transport in multiscale porous media via a proposed new general transport equation. A coherent theoretical derivation indicates the wall-molecule and molecule-molecule collisions drive the Knudsen and collective diffusive fluxes, and constitute the system pressure across the porous media. A new terminology, nominal diffusion coefficient can summarize Knudsen and collective diffusion coefficients. Physical and numerical experiments show the support of the new formulation and provide approaches to obtain the diffusion coefficient and permeability simultaneously. This work has important implication for natural gas extraction and greenhouse gases sequestration in geological formations.

Diffusion Rates of Organic Molecules in Secondary Organic Aerosol Particle

NASA Astrophysics Data System (ADS)

Bertram, A. K.; Chenyakin, Y.; Song, M.; Grayson, J. W.; Ullmann, D.; Evoy, E.; Renbaum-Wolff, L.; Liu, P.; Zhang, Y.; Kamal, S.; Martin, S. T.

2016-12-01

Information on the diffusion rates of organic molecules in secondary organic aerosol (SOA) particles are needed when predicting their size distribution, growth rates, photochemistry and heterogeneous chemistry. We have used two approaches to determine diffusion rates of organic molecules in SOA particles and proxies of SOA. In the first approach, we measured viscosities and then predicted diffusion rates using the Stokes-Einstein relation. In the second approach, we measured diffusion rates directly using a technique referred to as fluorescence recovery after photobleaching. Results from these measurements, including diffusion coefficients as a function of water activity, will be presented and the implications discussed.

Structural and water diffusion of poly(acryl amide)/poly(vinyl alcohol) blend films: Experiment and molecular dynamics simulations.

PubMed

Wang, Yanen; Wei, Qinghua; Wang, Shuzhi; Chai, Weihong; Zhang, Yingfeng

2017-01-01

To study the effects of composition ratios and temperature on the diffusion of water molecules in PVA/PAM blend films, five simulation models of PVA/PAM with ten water molecules at different composition ratios (4/0, 3/1, 2/2, 1/3, 0/4) were constructed and simulated by using a molecular dynamics (MD) simulation. The diffusion behavior of water molecules in blends were investigated from the aspects of the diffusion coefficient, free volume, pair correlation function (PCF) and trajectories of water molecules, respectively. And the hydrophilicity of blend composite was studied based on the contact angle and equilibrium water content (EWC) of the blend films. The simulation results show that the diffusion coefficient of water molecules and fractional free volume (FFV) of blend membranes increase with the addition of PAM, and a higher temperature can also improve the diffusion of water molecules. Additionally, the analysis of PCFs reveals the main reason why the diffusion coefficient of water in blend system increases with the addition of PAM. The measurement results of contact angle and EWC of blend films indicate that the hydrophilicity of blend films decreases with the addition of PAM, but the EWC of blends increases with the addition of PAM. Copyright © 2016 Elsevier Inc. All rights reserved.

Penetration of analogues of H2O and CO2 in proteins studied by room temperature phosphorescence of tryptophan.

PubMed

Wright, W W; Owen, C S; Vanderkooi, J M

1992-07-21

The influence of the protein matrix on the reactivity of external molecules with a species buried within the protein interior is considered in two general ways: (1) there may be structural fluctuations that allow for the diffusive penetration of the small molecules and/or (2) the external molecule may react over a distance. As a means to study the protein matrix, a reactive species within the protein can be formed by exciting tryptophan to the triplet state, and then the reaction of the triplet-state molecule with an external molecule can be monitored by a decrease in phosphorescence. In this work, the quenching ability (i.e., reactivity) was examined for H2S, CS2, and NO2- acting on tryptophan phosphorescence in parvalbumin, azurin, horse liver alcohol dehydrogenase, and alkaline phosphatase. A comparison of charged versus uncharged quenchers (H2S vs SH- and CS2 vs NO2-) reveals that the uncharged molecules are much more effective than charged species in quenching the phosphorescence of fully buried tryptophan, whereas the quenching for exposed tryptophan is relatively independent of the charge of the quencher. This is consistent with the view that uncharged triatomic molecules can penetrate the protein matrix to some extent. The energies of activation of the quenching reaction are low for the charged quenchers and higher for the uncharged CS2. A model is presented in which the quenchability of a buried tryptophan is inversely related to the distance from the surface when diffusion through the protein is the rate-limiting step.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP)

NASA Astrophysics Data System (ADS)

Snyder, David A.; Chantova, Mihaela; Chaudhry, Saadia

2015-06-01

NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase.

Facilitated transport of small molecules and ions for energy-efficient membranes.

PubMed

Li, Yifan; Wang, Shaofei; He, Guangwei; Wu, Hong; Pan, Fusheng; Jiang, Zhongyi

2015-01-07

In nature, the biological membrane can selectively transport essential small molecules/ions through facilitated diffusion via carrier proteins. Intrigued by this phenomenon and principle, membrane researchers have successfully employed synthetic carriers and carrier-mediated reversible reactions to enhance the separation performance of synthetic membranes. However, the existing facilitated transport membranes as well as the relevant facilitated transport theories have scarcely been comprehensively reviewed in the literature. This tutorial review primarily covers the two aspects of facilitated transport theories: carrier-mediated transport mechanisms and facilitated transport chemistries, including the design and fabrication of facilitated transport membranes. The applications of facilitated transport membranes in energy-intensive membrane processes (gas separation, pervaporation, and proton exchange membrane fuel cells) have also been discussed. Hopefully, this review will provide guidelines for the future research and development of facilitated transport membranes with high energy efficiency.

Selective photocatalytic transformations on microporous titanosilicate ETS-10 driven by size and polarity of molecules.

PubMed

Shiraishi, Yasuhiro; Tsukamoto, Daijiro; Hirai, Takayuki

2008-11-04

Photocatalytic activity of microporous titanosilicate ETS-10 has been studied in water. The photoactivated ETS-10 shows catalytic activity driven by size and polarity of substrates. ETS-10 efficiently catalyzes a conversion of substrates with a size larger than the pore diameter of ETS-10. In contrast, the reactivity of small substrates depends strongly on substrate polarity; less polar substrates show higher reactivity on ETS-10. Electron spin resonance analysis reveals that large substrates or less polar substrates scarcely diffuse inside the highly polarized micropores of ETS-10 and, hence, react efficiently with hydroxyl radicals (*OH) formed on titanol (Ti-OH) groups exposed on the external surface of ETS-10. In contrast, small polar substrates diffuse easily inside the micropores of ETS-10 and scarcely react with *OH, resulting in low reactivity. The photocatalytic activity of ETS-10 is successfully applicable to selective transformations of large reactants or less polar reactants to small polar products, enabling highly selective dehalogenation and hydroxylation of aromatics.

Imaging and quantification of trans-membrane protein diffusion in living bacteria.

PubMed

Oswald, Felix; L M Bank, Ernst; Bollen, Yves J M; Peterman, Erwin J G

2014-07-07

The cytoplasmic membrane forms the barrier between any cell's interior and the outside world. It contains many proteins that enable essential processes such as the transmission of signals, the uptake of nutrients, and cell division. In the case of prokaryotes, which do not contain intracellular membranes, the cytoplasmic membrane also contains proteins for respiration and protein folding. Mutual interactions and specific localization of these proteins depend on two-dimensional diffusion driven by thermal fluctuations. The experimental investigation of membrane-protein diffusion in bacteria is challenging due to their small size, only a few times larger than the resolution of an optical microscope. Here, we review fluorescence microscopy-based methods to study diffusion of membrane proteins in living bacteria. The main focus is on data-analysis tools to extract diffusion coefficients from single-particle tracking data obtained by single-molecule fluorescence microscopy. We introduce a novel approach, IPODD (inverse projection of displacement distributions), to obtain diffusion coefficients from the usually obtained 2-D projected diffusion trajectories of the highly 3-D curved bacterial membrane. This method provides, in contrast to traditional mean-squared-displacement methods, correct diffusion coefficients and allows unravelling of heterogeneously diffusing populations.

A hybrid continuous-discrete method for stochastic reaction–diffusion processes

PubMed Central

Zheng, Likun; Nie, Qing

2016-01-01

Stochastic fluctuations in reaction–diffusion processes often have substantial effect on spatial and temporal dynamics of signal transductions in complex biological systems. One popular approach for simulating these processes is to divide the system into small spatial compartments assuming that molecules react only within the same compartment and jump between adjacent compartments driven by the diffusion. While the approach is convenient in terms of its implementation, its computational cost may become prohibitive when diffusive jumps occur significantly more frequently than reactions, as in the case of rapid diffusion. Here, we present a hybrid continuous-discrete method in which diffusion is simulated using continuous approximation while reactions are based on the Gillespie algorithm. Specifically, the diffusive jumps are approximated as continuous Gaussian random vectors with time-dependent means and covariances, allowing use of a large time step, even for rapid diffusion. By considering the correlation among diffusive jumps, the approximation is accurate for the second moment of the diffusion process. In addition, a criterion is obtained for identifying the region in which such diffusion approximation is required to enable adaptive calculations for better accuracy. Applications to a linear diffusion system and two nonlinear systems of morphogens demonstrate the effectiveness and benefits of the new hybrid method. PMID:27703710

Diffusion properties of molecules at the blood-brain interface: potential contributions of astrocyte endfeet to diffusion barrier functions.

PubMed

Nuriya, Mutsuo; Shinotsuka, Takanori; Yasui, Masato

2013-09-01

Molecular diffusion in the extracellular space (ECS) plays a key role in determining tissue physiology and pharmacology. The blood-brain barrier regulates the exchange of substances between the brain and the blood, but the diffusion properties of molecules at this blood-brain interface, particularly around the astrocyte endfeet, are poorly characterized. In this study, we used 2-photon microscopy and acute brain slices of mouse neocortex and directly assessed the diffusion patterns of fluorescent molecules. By observing the diffusion of unconjugated and 10-kDa dextran-conjugated Alexa Fluor 488 from the ECS of the brain parenchyma to the blood vessels, we find various degrees of diffusion barriers at the endfeet: Some allow the invasion of dye inside the endfoot network while others completely block it. Detailed analyses of the time course for dye clearance support the existence of a tight endfoot network capable of acting as a diffusion barrier. Finally, we show that this diffusion pattern collapses under pathological conditions. These data demonstrate the heterogeneous nature of molecular diffusion dynamics around the endfeet and suggest that these structures can serve as the diffusion barrier. Therefore, astrocyte endfeet may add another layer of regulation to the exchange of molecules between blood vessels and brain parenchyma.

Evaporation enhancement in soils: a critical review

NASA Astrophysics Data System (ADS)

Rutten, Martine; van de Giesen, Nick

2015-04-01

Temperature gradients in the top layer of the soil are, especially during the daytime, steeper than would be expected if thermal conduction was the primary heat transfer mechanism. Evaporation seems to have significant influence on the soil heat budget. Only part of the surface soil heat flux is conducted downwards, increasing the soil temperatures, and part is used for evaporation, acting as a sink to the soil heat budget. For moist soils, the evaporation is limited by the transport of water molecules to the surface. The classical view is that water vapor is transported from the evaporation front to the surface by diffusion. Diffusion is mixing due to the random movement of molecules resulting in flattening concentration gradients. In soil, the diffusive vapor flux and the resulting latent heat flux are generally small. We found that transport enhancement is necessary in order to sustain vapor fluxes that are large enough to sustain latent heat fluxes, as well as being large enough to explain the observed temperature gradients. Enhancement of vapor diffusion is a known phenomenon, subject to debate on the explanations of underlying mechanism. In an extensive literature review on vapor enhancement in soils, the plausibility of various mechanisms was assessed. We reviewed mechanisms based on (combinations of) diffusive, viscous, buoyant, capillary and external pressure forces including: thermodiffusion, dispersion, Stefan's flow, Knudsen diffusion, liquid island effect, hydraulic lift, free convection, double diffusive convection and forced convection. The analysis of the order of magnitude of the mechanisms based on first principles clearly distinguished between plausible and implausible mechanisms. Thermodiffusion, Stefan's flow, Knudsen effects, liquid islands do not significantly contribute to enhanced evaporation. Double diffusive convection seemed unlikely due to lack of experimental evidence, but could not be completely excluded from the list of potential mechanisms. Hydraulic lift, the mechanism that small capillaries lift liquid water to the surface where it evaporates, does significantly contribute to enhanced evaporation from soils, also from dryer soils. The experimental evidence for and the theoretical underpinnings of this mechanism are convincing. However, we sought mechanisms that both explain enhanced evaporation and steep temperature gradients in the soil during the daytime. These often observed gradients consist of a sharp decrease of temperature with a depth up to the depth of the evaporation front. Hydraulic lift cannot explain this because the evaporation front is located at the surface. One remaining mechanism is forced convection due to atmospheric pressure fluctuations, also referred to as wind pumping. Wind pumping causes displacement and flow velocities too small for significant convective and too small for significant dispersive transport, when steady state dispersion formulations are used. However, experiments do indicate significant dispersive transport that can be explained by dispersion under unsteady flow conditions. Forced convection due to pressure fluctuations seems to be the only mechanism that can explain both enhanced evaporation and the steep temperature gradients.

A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects.

PubMed

Galgoczy, Roland; Pastor, Isabel; Colom, Adai; Giménez, Alicia; Mas, Francesc; Alcaraz, Jordi

2014-08-01

The design of 3D culture studies remains challenging due to the limited understanding of extracellular matrix (ECM)-dependent hindered diffusion and the lack of simple diffusivity assays. To address these limitations, we set up a cost-effective diffusivity assay based on a Transwell plate and the spectrophotometer of a Microplate Reader, which are readily accessible to cell biology groups. The spectrophotometer-based assay was used to assess the apparent diffusivity D of FITC-dextrans with molecular weight (4-70kDa) spanning the physiological range of signaling factors in a panel of acellular ECM gels including Matrigel, fibrin and type I collagen. Despite their technical differences, D data exhibited ∼15% relative difference with respect to FRAP measurements. Our results revealed that diffusion hindrance of small particles is controlled by the enhanced viscosity of the ECM gel in conformance with the Stokes-Einstein equation rather than by geometrical factors. Moreover, we provided a strong rationale that the enhanced ECM viscosity is largely contributed to by unassembled ECM macromolecules. We also reported that gels with the lowest D exhibited diffusion hindrance closest to the large physiologic hindrance of brain tissue, which has a typical pore size much smaller than ECM gels. Conversely, sparse gels (≤1mg/ml), which are extensively used in 3D cultures, failed to reproduce the hindered diffusion of tissues, thereby supporting that dense (but not sparse) ECM gels are suitable tissue surrogates in terms of macromolecular transport. Finally, the consequences of reduced diffusivity in terms of optimizing the design of 3D culture experiments were addressed in detail. Copyright © 2014 Elsevier B.V. All rights reserved.

Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc04643j

PubMed Central

Miguel-Ávila, Joan; Tomás-Gamasa, María; Olmos, Andrea

2018-01-01

The archetype reaction of “click” chemistry, namely, the copper-promoted azide–alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interior of mammalian cells, are essentially unknown. Herein we demonstrate that isolated, well-defined copper(i)–tris(triazolyl) complexes featuring designed ligands can readily enter mammalian cells and promote intracellular CuAAC annulations of small, freely diffusible molecules. In addition to simplifying protocols and avoiding the addition of “non-innocent” reductants, the use of these premade copper complexes leads to more efficient processes than with the alternative, in situ made copper species prepared from Cu(ii) sources, tris(triazole) ligands and sodium ascorbate. Under the reaction conditions, the well-defined copper complexes exhibit very good cell penetration properties, and do not present significant toxicities. PMID:29675241

Influence of cell shape, inhomogeneities and diffusion barriers in cell polarization models

NASA Astrophysics Data System (ADS)

Giese, Wolfgang; Eigel, Martin; Westerheide, Sebastian; Engwer, Christian; Klipp, Edda

2015-12-01

In silico experiments bear the potential for further understanding of biological transport processes by allowing a systematic modification of any spatial property and providing immediate simulation results. Cell polarization and spatial reorganization of membrane proteins are fundamental for cell division, chemotaxis and morphogenesis. We chose the yeast Saccharomyces cerevisiae as an exemplary model system which entails the shuttling of small Rho GTPases such as Cdc42 and Rho, between an active membrane-bound form and an inactive cytosolic form. We used partial differential equations to describe the membrane-cytosol shuttling of proteins. In this study, a consistent extension of a class of 1D reaction-diffusion systems into higher space dimensions is suggested. The membrane is modeled as a thin layer to allow for lateral diffusion and the cytosol is modeled as an enclosed volume. Two well-known polarization mechanisms were considered. One shows the classical Turing-instability patterns, the other exhibits wave-pinning dynamics. For both models, we investigated how cell shape and diffusion barriers like septin structures or bud scars influence the formation of signaling molecule clusters and subsequent polarization. An extensive set of in silico experiments with different modeling hypotheses illustrated the dependence of cell polarization models on local membrane curvature, cell size and inhomogeneities on the membrane and in the cytosol. In particular, the results of our computer simulations suggested that for both mechanisms, local diffusion barriers on the membrane facilitate Rho GTPase aggregation, while diffusion barriers in the cytosol and cell protrusions limit spontaneous molecule aggregations of active Rho GTPase locally.

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery.

PubMed

Römgens, Anne M; Bader, Dan L; Bouwstra, Joke A; Baaijens, Frank P T; Oomens, Cees W J

2015-10-01

Delivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the outer layer of the skin in therapeutic amounts, but also macromolecules. To provide insight into the administration of these molecules into the skin, the aim of this study was to assess the transport of macromolecules within and between its various layers. The diffusion coefficients in the epidermis and several locations in the papillary and reticular dermis were determined for fluorescein dextran of 40 and 500 kDa using a combination of fluorescent recovery after photobleaching experiments and finite element analysis. The diffusion coefficient was significantly higher for 40 kDa than 500 kDa dextran, with median values of 23 and 9 µm(2)/s in the dermis, respectively. The values only marginally varied within and between papillary and reticular dermis. For the 40 kDa dextran, the diffusion coefficient in the epidermis was twice as low as in the dermis layers. The adopted method may be used for other macromolecules, which are of interest for dermal and transdermal drug delivery. The knowledge about diffusion in the skin is useful to optimize (trans)dermal drug delivery systems to target specific layers or cells in the human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metal-atom Interactions and Clustering in Organic Semiconductor Systems

NASA Astrophysics Data System (ADS)

Tomita, Yoko; Park, Tea-uk; Nakayama, Takashi

2017-07-01

The interatomic interactions and clustering of metal atoms have been studied by first-principles calculations in graphene, pentacene, and polyacetylene as representative organic systems. It is shown that long-range repulsive Coulomb interaction appears between metal atoms with small electronegativity such as Al due to their ionization on host organic molecules, inducing their scattered distribution in organic systems. On the other hand, metal atoms with large electronegativity such as Au are weakly bonded to organic molecules, easily diffuse in molecular solids, and prefer to combine with each other owing to their short-range strong metallic-bonding interaction, promoting metal cluster generation in organic systems.

Various diffusion magnetic resonance imaging techniques for pancreatic cancer

PubMed Central

Tang, Meng-Yue; Zhang, Xiao-Ming; Chen, Tian-Wu; Huang, Xiao-Hua

2015-01-01

Pancreatic cancer is one of the most common malignant tumors and remains a treatment-refractory cancer with a poor prognosis. Currently, the diagnosis of pancreatic neoplasm depends mainly on imaging and which methods are conducive to detecting small lesions. Compared to the other techniques, magnetic resonance imaging (MRI) has irreplaceable advantages and can provide valuable information unattainable with other noninvasive or minimally invasive imaging techniques. Advances in MR hardware and pulse sequence design have particularly improved the quality and robustness of MRI of the pancreas. Diffusion MR imaging serves as one of the common functional MRI techniques and is the only technique that can be used to reflect the diffusion movement of water molecules in vivo. It is generally known that diffusion properties depend on the characterization of intrinsic features of tissue microdynamics and microstructure. With the improvement of the diffusion models, diffusion MR imaging techniques are increasingly varied, from the simplest and most commonly used technique to the more complex. In this review, the various diffusion MRI techniques for pancreatic cancer are discussed, including conventional diffusion weighted imaging (DWI), multi-b DWI based on intra-voxel incoherent motion theory, diffusion tensor imaging and diffusion kurtosis imaging. The principles, main parameters, advantages and limitations of these techniques, as well as future directions for pancreatic diffusion imaging are also discussed. PMID:26753059

The quantitative impact of the mesopore size on the mass transfer mechanism of the new 1.9μm fully porous Titan-C18 particles. I: analysis of small molecules.

PubMed

Gritti, Fabrice; Guiochon, Georges

2015-03-06

Previous data have shown that could deliver a minimum reduced plate height as small as 1.7. Additionally, the reduction of the mesopore size after C18 derivatization and the subsequent restriction for sample diffusivity across the Titan-C18 particles were found responsible for the unusually small value of the experimental optimum reduced velocity (5 versus 10 for conventional particles) and for the large values of the average reduced solid-liquid mass transfer resistance coefficients (0.032 versus 0.016) measured for a series of seven n-alkanophenones. The improvements in column efficiency made by increasing the average mesopore size of the Titan silica from 80 to 120Å are investigated from a quantitative viewpoint based on the accurate measurements of the reduced coefficients (longitudinal diffusion, trans-particle mass transfer resistance, and eddy diffusion) and of the intra-particle diffusivity, pore, and surface diffusion for the same series of n-alkanophenone compounds. The experimental results reveal an increase (from 0% to 30%) of the longitudinal diffusion coefficients for the same sample concentration distribution (from 0.25 to 4) between the particle volume and the external volume of the column, a 40% increase of the intra-particle diffusivity for the same sample distribution (from 1 to 7) between the particle skeleton volume and the bulk phase, and a 15-30% decrease of the solid-liquid mass transfer coefficient for the n-alkanophenone compounds. Pore and surface diffusion are increased by 60% and 20%, respectively. The eddy dispersion term and the maximum column efficiency (295000plates/m) remain virtually unchanged. The rate of increase of the total plate height with increasing the chromatographic speed is reduced by 20% and it is mostly controlled (75% and 70% for 80 and 120Å pore size) by the flow rate dependence of the eddy dispersion term. Copyright © 2015 Elsevier B.V. All rights reserved.

Using fluorescence correlation spectroscopy to study conformational changes in denatured proteins.

PubMed

Sherman, Eilon; Itkin, Anna; Kuttner, Yosef Yehuda; Rhoades, Elizabeth; Amir, Dan; Haas, Elisha; Haran, Gilad

2008-06-01

Fluorescence correlation spectroscopy (FCS) is a sensitive analytical tool that allows dynamics and hydrodynamics of biomolecules to be studied under a broad range of experimental conditions. One application of FCS of current interest is the determination of the size of protein molecules in the various states they sample along their folding reaction coordinate, which can be accessed through the measurement of diffusion coefficients. It has been pointed out that the analysis of FCS curves is prone to artifacts that may lead to erroneous size determination. To set the stage for FCS studies of unfolded proteins, we first show that the diffusion coefficients of small molecules as well as proteins can be determined accurately even in the presence of high concentrations of co-solutes that change the solution refractive index significantly. Indeed, it is found that the Stokes-Einstein relation between the measured diffusion coefficient and solution viscosity holds even in highly concentrated glycerol or guanidinium hydrochloride (GuHCl) solutions. These measurements form the basis for an investigation of the structure of the denatured state of two proteins, the small protein L and the larger, three-domain protein adenylate kinase (AK). FCS is found useful for probing expansion in the denatured state beyond the unfolding transition. It is shown that the denatured state of protein L expands as the denaturant concentration increases, in a process akin to the transition from a globule to a coil in polymers. This process continues at least up to 5 M GuHCl. On the other hand, the denatured state of AK does not seem to expand much beyond 2 M GuHCl, a result that is in qualitative accord with single-molecule fluorescence histograms. Because both the unfolding transition and the coil-globule transition of AK occur at a much lower denaturant concentration than those of protein L, a possible correlation between the two phenomena is suggested.

Toward Computational Design of High-Efficiency Photovoltaics from First-Principles

DTIC Science & Technology

2016-08-15

dependence of exciton diffusion in conjugated small molecules, Applied Physics Letters, (04 2014): 0. doi: 10.1063/1.4871303 Guangfen Wu, Zi Li, Xu...principle approach based on the time- dependent density functional theory (TDDFT) to describe exciton states, including energy levels and many-body wave... depends more sensitively on the dimension and crystallinity of the acceptor parallel to the interface than normal to the interface. Reorganization

Biomimetic light-harvesting funnels for re-directioning of diffuse light.

PubMed

Pieper, Alexander; Hohgardt, Manuel; Willich, Maximilian; Gacek, Daniel Alexander; Hafi, Nour; Pfennig, Dominik; Albrecht, Andreas; Walla, Peter Jomo

2018-02-14

Efficient sunlight harvesting and re-directioning onto small areas has great potential for more widespread use of precious high-performance photovoltaics but so far intrinsic solar concentrator loss mechanisms outweighed the benefits. Here we present an antenna concept allowing high light absorption without high reabsorption or escape-cone losses. An excess of randomly oriented pigments collects light from any direction and funnels the energy to individual acceptors all having identical orientations and emitting ~90% of photons into angles suitable for total internal reflection waveguiding to desired energy converters (funneling diffuse-light re-directioning, FunDiLight). This is achieved using distinct molecules that align efficiently within stretched polymers together with others staying randomly orientated. Emission quantum efficiencies can be >80% and single-foil reabsorption <0.5%. Efficient donor-pool energy funneling, dipole re-orientation, and ~1.5-2 nm nearest donor-acceptor transfer occurs within hundreds to ~20 ps. Single-molecule 3D-polarization experiments confirm nearly parallel emitters. Stacked pigment selection may allow coverage of the entire solar spectrum.

Handheld Diffusion Test Cells

NASA Technical Reports Server (NTRS)

2001-01-01

This photo shows the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells (inside the plastic box) will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

Handheld Diffusion Test Cells

NASA Technical Reports Server (NTRS)

2001-01-01

This photo shows an individual cell from the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

Adsorption of small inorganic molecules on a defective MoS2 monolayer.

PubMed

González, César; Biel, Blanca; Dappe, Yannick J

2017-04-05

We present a theoretical study of molecular adsorption on defects on a MoS 2 monolayer. Based on Density Functional Theory, our calculations confirm that small inorganic molecules, such as CO 2 , CO, H 2 O, NO, NO 2 , H 2 and N 2 , remain bonded to the pristine monolayer through weak van der Waals interactions, suggesting that the molecules may easily diffuse over the clean monolayer. On the other hand, the introduction of defects can lead to three different situations, depending on the defect and the molecule considered: physisorption, chemical (strong) bonding to the metallic defects, namely the Mo substitutional atoms on the S vacancies, and dissociation, that can take place spontaneously at 0 K in some specific cases or by the effect of thermal agitation in molecules such as CO 2 or NO 2 on the S vacancy. Our energetic and electronic analyses provide an explanation to such bonding possibilities, showing that in the low interacting situations, the molecules tend to adopt a planar configuration parallel to the monolayer, while a molecular rotation is favored in order to facilitate the bond formation on the reactive sites. Finally, the ab initio based Scanning Tunneling Microscopy (STM) simulations show the fingerprint of each molecule adsorbed on the most reactive site. This work opens the way to the possibility of tuning the catalytic properties of MoS 2 by controlling the creation of specific defects in the MoS 2 monolayer.

Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling

DOE PAGES

Lv, Chao; Aitchison, Erick W.; Wu, Dongsheng; ...

2015-06-29

Hydrogen sulfide (H 2S), a commonly known toxic gas compound, possesses unique chemical features that allow this small solute molecule to quickly diffuse through cell membranes. Taking advantage of the recent orthogonal space tempering (OST) method, we comparatively mapped the transmembrane free energy landscapes of H 2S and its structural analogue, water (H 2O), seeking to decipher the molecular determinants that govern their drastically different permeabilities. Here, as revealed by our OST sampling results, in contrast to the highly polar water solute, hydrogen sulfide is evidently amphipathic, and thus inside membrane is favorably localized at the interfacial region, that is,more » the interface between the polar head-group and nonpolar acyl chain regions. Because the membrane binding affinity of H 2S is mainly governed by its small hydrophobic moiety and the barrier height inbetween the interfacial region and the membrane center is largely determined by its moderate polarity, the transmembrane free energy barriers to encounter by this toxic molecule are very small. Moreover when H2S diffuses from the bulk solution to the membrane center, the above two effects nearly cancel each other, so as to lead to a negligible free energy difference. Lastly, this study not only explains why H 2S can quickly pass through cell membranes but also provides a practical illustration on how to use the OST free energy sampling method to conveniently analyze complex molecular processes.« less

Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling.

PubMed

Lv, Chao; Aitchison, Erick W; Wu, Dongsheng; Zheng, Lianqing; Cheng, Xiaolin; Yang, Wei

2016-03-05

Hydrogen sulfide (H2 S), a commonly known toxic gas compound, possesses unique chemical features that allow this small solute molecule to quickly diffuse through cell membranes. Taking advantage of the recent orthogonal space tempering (OST) method, we comparatively mapped the transmembrane free energy landscapes of H2 S and its structural analogue, water (H2 O), seeking to decipher the molecular determinants that govern their drastically different permeabilities. As revealed by our OST sampling results, in contrast to the highly polar water solute, hydrogen sulfide is evidently amphipathic, and thus inside membrane is favorably localized at the interfacial region, that is, the interface between the polar head-group and nonpolar acyl chain regions. Because the membrane binding affinity of H2 S is mainly governed by its small hydrophobic moiety and the barrier height inbetween the interfacial region and the membrane center is largely determined by its moderate polarity, the transmembrane free energy barriers to encounter by this toxic molecule are very small. Moreover when H2 S diffuses from the bulk solution to the membrane center, the above two effects nearly cancel each other, so as to lead to a negligible free energy difference. This study not only explains why H2 S can quickly pass through cell membranes but also provides a practical illustration on how to use the OST free energy sampling method to conveniently analyze complex molecular processes. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Visualizing repetitive diffusion activity of double-strand RNA binding proteins by single molecule fluorescence assays.

PubMed

Koh, Hye Ran; Wang, Xinlei; Myong, Sua

2016-08-01

TRBP, one of double strand RNA binding proteins (dsRBPs), is an essential cofactor of Dicer in the RNA interference pathway. Previously we reported that TRBP exhibits repetitive diffusion activity on double strand (ds)RNA in an ATP independent manner. In the TRBP-Dicer complex, the diffusion mobility of TRBP facilitates Dicer-mediated RNA cleavage. Such repetitive diffusion of dsRBPs on a nucleic acid at the nanometer scale can be appropriately captured by several single molecule detection techniques. Here, we provide a step-by-step guide to four different single molecule fluorescence assays by which the diffusion activity of dsRBPs on dsRNA can be detected. One color assay, termed protein induced fluorescence enhancement enables detection of unlabeled protein binding and diffusion on a singly labeled RNA. Two-color Fluorescence Resonance Energy Transfer (FRET) in which labeled dsRBPs is applied to labeled RNA, allows for probing the motion of protein along the RNA axis. Three color FRET reports on the diffusion movement of dsRBPs from one to the other end of RNA. The single molecule pull down assay provides an opportunity to collect dsRBPs from mammalian cells and examine the protein-RNA interaction at single molecule platform. Copyright © 2016 Elsevier Inc. All rights reserved.

Single Molecule Spectral Diffusion in a Solid Detected Via Fluorescence Spectroscopy

DTIC Science & Technology

1991-10-15

other local fields) at the position of the molecule, the spectral jumps may occur because the class II pentacene molecules are coupled to an...and identify by block number) FIELD jGROUP SUB-GROUP_ Single molecule spectroscopy Precision detection Spectral diffusion, Pentacene in p-terphenyl 19...significant increases in detection sensitivity for single pentacene molecules in crystals of p-terphenyl at low temperatures. With the increased signal to

Method of fabricating an optoelectronic device having a bulk heterojunction

DOEpatents

Shtein, Max [Ann Arbor, MI; Yang, Fan [Princeton, NJ; Forrest, Stephen R [Princeton, NJ

2008-10-14

A method of fabricating an optoelectronic device comprises: depositing a first layer having protrusions over a first electrode, in which the first layer comprises a first organic small molecule material; depositing a second layer on the first layer such that the second layer is in physical contact with the first layer; in which the smallest lateral dimension of the protrusions are between 1 to 5 times the exciton diffusion length of the first organic small molecule material; and depositing a second electrode over the second layer to form the optoelectronic device. A method of fabricating an organic optoelectronic device having a bulk heterojunction is also provided and comprises: depositing a first layer with protrusions over an electrode by organic vapor phase deposition; depositing a second layer on the first layer where the interface of the first and second layers forms a bulk heterojunction; and depositing another electrode over the second layer.

110 Years of the Meyer–Overton Rule: Predicting Membrane Permeability of Gases and Other Small Compounds

PubMed Central

Missner, Andreas; Pohl, Peter

2010-01-01

The transport of gaseous compounds across biological membranes is essential in all forms of life. Although it was generally accepted that gases freely penetrate the lipid matrix of biological membranes, a number of studies challenged this doctrine as they found biological membranes to have extremely low gas-permeability values. These observations led to the identification of several membrane-embedded “gas” channels, which facilitate the transport of biological active gases, such as carbon dioxide, nitric oxide, and ammonia. However, some of these findings are in contrast to the well-established solubility–diffusion model (also known as the Meyer–Overton rule), which predicts membrane permeabilities from the molecule's oil–water partition coefficient. Herein, we discuss recently reported violations of the Meyer–Overton rule for small molecules, including carboxylic acids and gases, and show that Meyer and Overton continue to rule. PMID:19514034

Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging.

PubMed

Kikuchi, Shingo; Onuki, Yoshinori; Kuribayashi, Hideto; Takayama, Kozo

2012-01-01

We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.

Multi-Algorithm Particle Simulations with Spatiocyte.

PubMed

Arjunan, Satya N V; Takahashi, Koichi

2017-01-01

As quantitative biologists get more measurements of spatially regulated systems such as cell division and polarization, simulation of reaction and diffusion of proteins using the data is becoming increasingly relevant to uncover the mechanisms underlying the systems. Spatiocyte is a lattice-based stochastic particle simulator for biochemical reaction and diffusion processes. Simulations can be performed at single molecule and compartment spatial scales simultaneously. Molecules can diffuse and react in 1D (filament), 2D (membrane), and 3D (cytosol) compartments. The implications of crowded regions in the cell can be investigated because each diffusing molecule has spatial dimensions. Spatiocyte adopts multi-algorithm and multi-timescale frameworks to simulate models that simultaneously employ deterministic, stochastic, and particle reaction-diffusion algorithms. Comparison of light microscopy images to simulation snapshots is supported by Spatiocyte microscopy visualization and molecule tagging features. Spatiocyte is open-source software and is freely available at http://spatiocyte.org .

Nonisothermal Brownian motion: Thermophoresis as the macroscopic manifestation of thermally biased molecular motion.

PubMed

Brenner, Howard

2005-12-01

A quiescent single-component gravity-free gas subject to a small steady uniform temperature gradient T, despite being at rest, is shown to experience a drift velocity UD=-D* gradient ln T, where D* is the gas's nonisothermal self-diffusion coefficient. D* is identified as being the gas's thermometric diffusivity alpha. The latter differs from the gas's isothermal isotopic self-diffusion coefficient D, albeit only slightly. Two independent derivations are given of this drift velocity formula, one kinematical and the other dynamical, both derivations being strictly macroscopic in nature. Within modest experimental and theoretical uncertainties, this virtual drift velocity UD=-alpha gradient ln T is shown to be constitutively and phenomenologically indistinguishable from the well-known experimental and theoretical formulas for the thermophoretic velocity U of a macroscopic (i.e., non-Brownian) non-heat-conducting particle moving under the influence of a uniform temperature gradient through an otherwise quiescent single-component rarefied gas continuum at small Knudsen numbers. Coupled with the size independence of the particle's thermophoretic velocity, the empirically observed equality, U=UD, leads naturally to the hypothesis that these two velocities, the former real and the latter virtual, are, in fact, simply manifestations of the same underlying molecular phenomenon, namely the gas's Brownian movement, albeit biased by the temperature gradient. This purely hydrodynamic continuum-mechanical equality is confirmed by theoretical calculations effected at the kinetic-molecular level on the basis of an existing solution of the Boltzmann equation for a quasi-Lorentzian gas, modulo small uncertainties pertaining to the choice of collision model. Explicitly, this asymptotically valid molecular model allows the virtual drift velocity UD of the light gas and the thermophoretic velocity U of the massive, effectively non-Brownian, particle, now regarded as the tracer particle of the light gas's drift velocity, to each be identified with the Chapman-Enskog "thermal diffusion velocity" of the quasi-Lorentzian gas, here designated by the symbol UM/M, as calculated by de la Mora and Mercer. It is further pointed out that, modulo the collective uncertainties cited above, the common velocities UD,U, and UM/M are identical to the single-component gas's diffuse volume current jv, the latter representing yet another, independent, strictly continuum-mechanical concept. Finally, comments are offered on the extension of the single-component drift velocity notion to liquids, and its application towards rationalizing Soret thermal-diffusion separation phenomena in quasi-Lorentzian liquid-phase binary mixtures composed of disparately sized solute and solvent molecules, with the massive Brownian solute molecules (e.g., colloidal particles) present in disproportionately small amounts relative to that of the solvent.

Techniques to measure sorption and migration between small molecules and packaging. A critical review.

PubMed

Kadam, Ashish A; Karbowiak, Thomas; Voilley, Andrée; Debeaufort, Frédéric

2015-05-01

The mass transfer parameters diffusion and sorption in food and packaging or between them are the key parameters for assessing a food product's shelf-life in reference to consumer safety. This has become of paramount importance owing to the legislations set by the regulated markets. The technical capabilities that can be exploited for analyzing product-package interactions have been growing rapidly. Different techniques categorized according to the state of the diffusant (gas or liquid) in contact with the packaging material are emphasized in this review. Depending on the diffusant and on the analytical question under review, the different ways to study sorption and/or migration are presented and compared. Some examples have been suggested to reach the best possible choice, consisting of a single technique or a combination of different approaches. © 2014 Society of Chemical Industry.

Study of water diffusion on single-supported bilayer lipid membranes by quasielastic neutron scattering

NASA Astrophysics Data System (ADS)

Bai, M.; Miskowiec, A.; Hansen, F. Y.; Taub, H.; Jenkins, T.; Tyagi, M.; Diallo, S. O.; Mamontov, E.; Herwig, K. W.; Wang, S.-K.

2012-05-01

High-energy-resolution quasielastic neutron scattering has been used to elucidate the diffusion of water molecules in proximity to single bilayer lipid membranes supported on a silicon substrate. By varying sample temperature, level of hydration, and deuteration, we identify three different types of diffusive water motion: bulk-like, confined, and bound. The motion of bulk-like and confined water molecules is fast compared to those bound to the lipid head groups (7-10 H2O molecules per lipid), which move on the same nanosecond time scale as H atoms within the lipid molecules.

Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP).

PubMed

Snyder, David A; Chantova, Mihaela; Chaudhry, Saadia

2015-06-01

NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase. Copyright © 2015 Elsevier Inc. All rights reserved.

Structure and dynamics of water and lipid molecules in charged anionic DMPG lipid bilayer membranes

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

Rønnest, A. K.; Peters, G. H.; Hansen, F. Y., E-mail: flemming@kemi.dtu.dk

2016-04-14

Molecular dynamics simulations have been used to investigate the influence of the valency of counter-ions on the structure of freestanding bilayer membranes of the anionic 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) lipid at 310 K and 1 atm. At this temperature, the membrane is in the fluid phase with a monovalent counter-ion and in the gel phase with a divalent counter-ion. The diffusion constant of water as a function of its depth in the membrane has been determined from mean-square-displacement calculations. Also, calculated incoherent quasielastic neutron scattering functions have been compared to experimental results and used to determine an average diffusion constant for allmore » water molecules in the system. On extrapolating the diffusion constants inferred experimentally to a temperature of 310 K, reasonable agreement with the simulations is obtained. However, the experiments do not have the sensitivity to confirm the diffusion of a small component of water bound to the lipids as found in the simulations. In addition, the orientation of the dipole moment of the water molecules has been determined as a function of their depth in the membrane. Previous indirect estimates of the electrostatic potential within phospholipid membranes imply an enormous electric field of 10{sup 8}–10{sup 9} V m{sup −1}, which is likely to have great significance in controlling the conformation of translocating membrane proteins and in the transfer of ions and molecules across the membrane. We have calculated the membrane potential for DMPG bilayers and found ∼1 V (∼2 ⋅ 10{sup 8} V m{sup −1}) when in the fluid phase with a monovalent counter-ion and ∼1.4 V (∼2.8 ⋅ 10{sup 8} V m{sup −1}) when in the gel phase with a divalent counter-ion. The number of water molecules for a fully hydrated DMPG membrane has been estimated to be 9.7 molecules per lipid in the gel phase and 17.5 molecules in the fluid phase, considerably smaller than inferred experimentally for 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) membranes but comparable to the number inferred for 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE) membranes. Some of the properties of the DMPG membrane are compared with those of the neutral zwitterionic DMPC bilayer membrane at 303 K and 1 atm, which is the same reduced temperature with respect to the gel-to-fluid transition temperature as 310 K is for the DMPG bilayer membrane.« less

Dynamics of Phenanthrenequinone on Carbon Nano-Onion Surfaces Probed by Quasielastic Neutron Scattering

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

Anjos, Daniela M; Mamontov, Eugene; Brown, Gilbert M

We used quasielastic neutron scattering (QENS) to study the dynamics of phenanthrenequinone (PQ) on the surface of onion-like carbon (OLC), or so called carbon onions, as a function of surface coverage and temperature. For both the high- and low-coverage samples, we observed two diffusion processes; a faster process and nearly an order of magnitude slower process. On the high-coverage surface, the slow diffusion process is of long-range translational character, whereas the fast diffusion process is spatially localized on the length scale of ~ 4.7 . On the low-coverage surface, both diffusion processes are spatially localized; on the same length scalemore » of ~ 4.7 for the fast diffusion and a somewhat larger length scale for the slow diffusion. Arrhenius temperature dependence is observed except for the long-range diffusion on the high-coverage surface. We attribute the fast diffusion process to the generic localized in-cage dynamics of PQ molecules, and the slow diffusion process to the long-range translational dynamics of PQ molecules, which, depending on the coverage, may be either spatially restricted, or long-range. On the low-coverage surface, uniform surface coverage is not attained, and the PQ molecules experience the effect of spatial constraints on their long-range translational dynamics. Unexpectedly, the dynamics of PQ molecules on OLC as a function of temperature and surface coverage bears qualitative resemblance to the dynamics of water molecules on oxide surfaces, including practically temperature-independent residence times for the low-coverage surface. The dynamics features that we observed may be universal across different classes of surface adsorbates.« less

Diffusion of aqueous solutions of ionic, zwitterionic, and polar solutes

NASA Astrophysics Data System (ADS)

Teng, Xiaojing; Huang, Qi; Dharmawardhana, Chamila Chathuranga; Ichiye, Toshiko

2018-06-01

The properties of aqueous solutions of ionic, zwitterionic, and polar solutes are of interest to many fields. For instance, one of the many anomalous properties of aqueous solutions is the behavior of water diffusion in different monovalent salt solutions. In addition, solutes can affect the stabilities of macromolecules such as proteins in aqueous solution. Here, the diffusivities of aqueous solutions of sodium chloride, potassium chloride, tri-methylamine oxide (TMAO), urea, and TMAO-urea are examined in molecular dynamics simulations. The decrease in the diffusivity of water with the concentration of simple ions and urea can be described by a simple model in which the water molecules hydrogen bonded to the solutes are considered to diffuse at the same rate as the solutes, while the remainder of the water molecules are considered to be bulk and diffuse at almost the same rate as pure water. On the other hand, the decrease in the diffusivity of water with the concentration of TMAO is apparently affected by a decrease in the diffusion rate of the bulk water molecules in addition to the decrease due to the water molecules hydrogen bonded to TMAO. In other words, TMAO enhances the viscosity of water, while urea barely affects it. Overall, this separation of water molecules into those that are hydrogen bonded to solute and those that are bulk can provide a useful means of understanding the short- and long-range effects of solutes on water.

Detection of cortisol in saliva with a flow-filtered, portable surface plasmon resonance biosensor system

PubMed Central

Stevens, Richard C.; Soelberg, Scott D.; Near, Steve; Furlong, Clement E.

2011-01-01

Saliva provides a useful and non-invasive alternative to blood for many biomedical diagnostic assays. The level of the hormone cortisol in blood and saliva is related to the level of stress. We present here the development of a portable surface plasmon resonance (SPR) biosensor system for detection of cortisol in saliva. Cortisol-specific monoclonal antibodies were used to develop a competition assay with a 6-channel portable SPR biosensor designed in our laboratory. The detection limit of cortisol in laboratory buffers was 0.36 ng/ml (1.0 nM). An in-line filter based on diffusion through a hollow fiber hydrophilic membrane served to separate small molecules from the complex macromolecular matrix of saliva prior to introduction to the sensor surface. The filtering flow cell provided in-line separation of small molecules from salivary mucins and other large molecules with only a 29% reduction of signal compared with direct flow of the same concentration of analyte over the sensor surface. A standard curve for detection of cortisol in saliva was generated with a detection limit of 1.0 ng/ml (3.6 nM), sufficiently sensitive for clinical use. The system will also be useful for a wide range of applications where small molecular weight analytes are found in complex matrices. PMID:18656950

Effect of Aggregation on Squaraine Fullerene Bulk-Heterojunction Organic Photovoltaic Devices

NASA Astrophysics Data System (ADS)

Jalan, Ishita

Organic photovoltaics (OPV) offer great promise as a low-cost renewable energy source, the relative low efficiency still challenges its commercialization potential. Small conjugated molecules like Squaraine (SQ) molecules show promising advancement in organic photovoltaics (OPV). Advantages of SQ over other materials is that it has a high extinction coefficient (>105), decent photo-stability, good synthetic reproducibility, and tunable molecular structure. With small chemical modifications, the squaraines can have substantial impact on photophysical properties and aggregation pattern, and thus on operational OPV efficiency. The squaraine molecule that will be studied in this work is a symmetric aniline-based squaraine with n-hexyl chain on the molecular arm with di hydroxyl substituents on the aniline, this will be referred to DHSQ(OH) 2. In this work, the assignment of the monomer and aggregate peak is discussed. It is known that crystallinity is important for efficient charge transport and exciton diffusion in the BHJ, this thesis focuses on thermal and solvent vapor annealing the as-cast films to reduce the amorphous regions. It is observed that crystallinity is improved but often at the expense of larger crystal size. Therefore, to achieve optimal OPV efficiency, this tradeoff is controlled to improve the crystallinity while maintaining a small, highly mixed BHJ morphology.

Effects of Shapes of Solute Molecules on Diffusion: A Study of Dependences on Solute Size, Solvent, and Temperature.

PubMed

Chan, T C; Li, H T; Li, K Y

2015-12-24

Diffusivities of basically linear, planar, and spherical solutes at infinite dilution in various solvents are studied to unravel the effects of solute shapes on diffusion. On the basis of the relationship between the reciprocal of diffusivity and the molecular volume of solute molecules with similar shape in a given solvent at constant temperature, the diffusivities of solutes of equal molecular volume but different shapes are evaluated and the effects due to different shapes of two equal-sized solute molecules on diffusion are determined. It is found that the effects are dependent on the size of the solute pairs studied. Evidence of the dependence of the solute-shape effects on solvent properties is also demonstrated and discussed. Here, some new diffusion data of aromatic compounds in methanol at different temperatures are reported. The result for methanol in this study indicates that the effects of solute shape on diffusivity are only weakly dependent on temperature.

Characterization of the organic ligand shell of semiconductor quantum dots by fluorescence quenching experiments.

PubMed

Boldt, Klaus; Jander, Sebastian; Hoppe, Kathrin; Weller, Horst

2011-10-25

We present the characterization of the organic ligand shell of CdSe/Cd(x)Zn(1-x)S/ZnS nanoparticles by means of fluorescence quenching experiments. Both electron scavengers and acceptors for resonance energy transfer were employed as probes. Different quenching behavior for short and long chain thiol ligands in water was found. It could be shown that poly(ethylene oxide) (PEO)-capping of the particles comprises a densely packed inner shell and a loosely packed outer shell in which ions and small molecules diffuse unhindered. A quantitative uptake of quencher molecules into the PEO shell was observed, through which the particle volume including the ligand sphere could be determined.

Diffusion of flexible, charged, nanoscopic molecules in solution: Size and pH dependence for PAMAM dendrimer

NASA Astrophysics Data System (ADS)

Maiti, Prabal K.; Bagchi, Biman

2009-12-01

In order to understand self-diffusion (D) of a charged, flexible, and porous nanoscopic molecule in water, we carry out very long, fully atomistic molecular dynamics simulation of PAMAM dendrimer up to eight generations in explicit salt water under varying pH. We find that while the radius of gyration (Rg) varies as N1/3, the self-diffusion constant (D ) scales, surprisingly, as N-α, with α =0.39 at high pH and 0.5 at neutral pH, indicating a dramatic breakdown of Stokes-Einstein relation for diffusion of charged nanoscopic molecules. The variation in D as a function of radius of gyration demonstrates the importance of treating water and ions explicitly in the diffusion process of a flexible nanoscopic molecule. In agreement with recent experiments, the self-diffusion constant increases with pH, revealing the importance of dielectric friction in the diffusion process. The shape of a dendrimer is found to fluctuate on a nanosecond time scale. We argue that this flexibility (and also the porosity) of the dendrimer may play an important role in determining the mean square displacement of the dendrimer and the breakdown of the Stokes-Einstein relation between diffusion constant and the radius.

Is the wall of a cellulose fiber saturated with liquid whether or not permeable with CO2 dissolved molecules? Application to bubble nucleation in champagne wines.

PubMed

Liger-Belair, Gérard; Topgaard, Daniel; Voisin, Cédric; Jeandet, Philippe

2004-05-11

In this paper, the transversal diffusion coefficient D perpendicular of CO2 dissolved molecules through the wall of a hydrated cellulose fiber was approached, from the liquid bulk diffusion coefficient of CO2 dissolved molecules modified by an obstruction factor. The porous network between the cellulose microfibrils of the fiber wall was assumed being saturated with liquid. We retrieved information from previous NMR experiments on the self-diffusion of water in cellulose fibers to reach an order of magnitude for the transversal diffusion coefficient of CO2 molecules through the fiber wall. A value of about D perpendicular approximately 0.2D0 was proposed, D0 being the diffusion coefficient of CO2 molecules in the liquid bulk. Because most of bubble nucleation sites in a glass poured with carbonated beverage are cellulose fibers cast off from paper or cloth which floated from the surrounding air, or remaining from the wiping process, this result directly applies to the kinetics of carbon dioxide bubble formation from champagne and sparkling wines. If the cellulose fiber wall was impermeable with regard to CO2 dissolved molecules, it was suggested that the kinetics of bubbling would be about three times less than it is.

Multiple Diffusion Mechanisms Due to Nanostructuring in Crowded Environments

PubMed Central

Sanabria, Hugo; Kubota, Yoshihisa; Waxham, M. Neal

2007-01-01

One of the key questions regarding intracellular diffusion is how the environment affects molecular mobility. Mostly, intracellular diffusion has been described as hindered, and the physical reasons for this behavior are: immobile barriers, molecular crowding, and binding interactions with immobile or mobile molecules. Using results from multi-photon fluorescence correlation spectroscopy, we describe how immobile barriers and crowding agents affect translational mobility. To study the hindrance produced by immobile barriers, we used sol-gels (silica nanostructures) that consist of a continuous solid phase and aqueous phase in which fluorescently tagged molecules diffuse. In the case of molecular crowding, translational mobility was assessed in increasing concentrations of 500 kDa dextran solutions. Diffusion of fluorescent tracers in both sol-gels and dextran solutions shows clear evidence of anomalous subdiffusion. In addition, data from the autocorrelation function were analyzed using the maximum entropy method as adapted to fluorescence correlation spectroscopy data and compared with the standard model that incorporates anomalous diffusion. The maximum entropy method revealed evidence of different diffusion mechanisms that had not been revealed using the anomalous diffusion model. These mechanisms likely correspond to nanostructuring in crowded environments and to the relative dimensions of the crowding agent with respect to the tracer molecule. Analysis with the maximum entropy method also revealed information about the degree of heterogeneity in the environment as reported by the behavior of diffusive molecules. PMID:17040979

A network of discrete events for the representation and analysis of diffusion dynamics.

PubMed

Pintus, Alberto M; Pazzona, Federico G; Demontis, Pierfranco; Suffritti, Giuseppe B

2015-11-14

We developed a coarse-grained description of the phenomenology of diffusive processes, in terms of a space of discrete events and its representation as a network. Once a proper classification of the discrete events underlying the diffusive process is carried out, their transition matrix is calculated on the basis of molecular dynamics data. This matrix can be represented as a directed, weighted network where nodes represent discrete events, and the weight of edges is given by the probability that one follows the other. The structure of this network reflects dynamical properties of the process of interest in such features as its modularity and the entropy rate of nodes. As an example of the applicability of this conceptual framework, we discuss here the physics of diffusion of small non-polar molecules in a microporous material, in terms of the structure of the corresponding network of events, and explain on this basis the diffusivity trends observed. A quantitative account of these trends is obtained by considering the contribution of the various events to the displacement autocorrelation function.

Probing the infrared counterparts of diffuse far-ultraviolet sources in the Galaxy

NASA Astrophysics Data System (ADS)

Saikia, Gautam; Shalima, P.; Gogoi, Rupjyoti; Pathak, Amit

2017-12-01

Recent availability of high quality infrared (IR) data for diffuse regions in the Galaxy and external galaxies have added to our understanding of interstellar dust. A comparison of ultraviolet (UV) and IR observations may be used to estimate absorption, scattering and thermal emission from interstellar dust. In this paper, we report IR and UV observations for selective diffuse sources in the Galaxy. Using archival mid-infrared (MIR) and far-infrared (FIR) observations from Spitzer Space Telescope, we look for counterparts of diffuse far-ultraviolet (FUV) sources observed by the Voyager, Far Ultraviolet Spectroscopic Explorer (FUSE) and Galaxy Evolution Explorer (GALEX) telescopes in the Galaxy. IR emission features at 8 μm are generally attributed to Polycyclic Aromatic Hydrocarbon (PAH) molecules, while emission at 24 μm are attributed to Very Small Grains (VSGs). The data presented here is unique and our study tries to establish a relation between various dust populations. By studying the FUV-IR correlations separately at low and high latitude locations, we have identified the grain component responsible for the diffuse FUV emission.

Supramolecular organization of the sperm plasma membrane during maturation and capacitation.

PubMed

Jones, Roy; James, Peter S; Howes, Liz; Bruckbauer, Andreas; Klenerman, David

2007-07-01

In the present study, a variety of high resolution microscopy techniques were used to visualize the organization and motion of lipids and proteins in the sperm's plasma membrane. We have addressed questions such as the presence of diffusion barriers, confinement of molecules to specific surface domains, polarized diffusion and the role of cholesterol in regulating lipid rafts and signal transduction during capacitation. Atomic force microscopy identified a novel region (EqSS) within the equatorial segment of bovine, porcine and ovine spermatozoa that was enriched in constitutively phosphorylated proteins. The EqSS was assembled during epididymal maturation. Fluorescence imaging techniques were then used to follow molecular diffusion on the sperm head. Single lipid molecules were freely exchangeable throughout the plasma membrane and showed no evidence for confinement within domains. Large lipid aggregates, however, did not cross over the boundary between the post-acrosome and equatorial segment suggesting the presence of a molecular filter between these two domains. A small reduction in membrane cholesterol enlarges or increases lipid rafts concomitant with phosphorylation of intracellular proteins. Excessive removal of cholesterol, however, disorganizes rafts with a cessation of phosphorylation. These techniques are forcing a revision of long-held views on how lipids and proteins in sperm membranes are assembled into larger complexes that mediate recognition and fusion with the egg.

Understanding and controlling regime switching in molecular diffusion

NASA Astrophysics Data System (ADS)

Hallerberg, S.; de Wijn, A. S.

2014-12-01

Diffusion can be strongly affected by ballistic flights (long jumps) as well as long-lived sticking trajectories (long sticks). Using statistical inference techniques in the spirit of Granger causality, we investigate the appearance of long jumps and sticks in molecular-dynamics simulations of diffusion in a prototype system, a benzene molecule on a graphite substrate. We find that specific fluctuations in certain, but not all, internal degrees of freedom of the molecule can be linked to either long jumps or sticks. Furthermore, by changing the prevalence of these predictors with an outside influence, the diffusion of the molecule can be controlled. The approach presented in this proof of concept study is very generic and can be applied to larger and more complex molecules. Additionally, the predictor variables can be chosen in a general way so as to be accessible in experiments, making the method feasible for control of diffusion in applications. Our results also demonstrate that data-mining techniques can be used to investigate the phase-space structure of high-dimensional nonlinear dynamical systems.

Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy

PubMed Central

Webb, Thomas R; Slavish, Jake; George, Rani E; Look, A Thomas; Xue, Liquan; Jiang, Qin; Cui, Xiaoli; Rentrop, Walter B; Morris, Stephan W

2009-01-01

Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase in the insulin receptor superfamily, was initially identified in constitutively activated oncogenic fusion forms – the most common being nucleophosmin-ALK – in anaplastic large-cell lymphomas, and subsequent studies have identified ALK fusions in diffuse large B-cell lymphomas, systemic histiocytosis, inflammatory myofibroblastic tumors, esophageal squamous cell carcinomas and non-small-cell lung carcinomas. More recently, genomic DNA amplification and protein overexpression, as well as activating point mutations, of ALK have been described in neuroblastomas. In addition to those cancers for which a causative role for aberrant ALK activity is well validated, more circumstantial links implicate the full-length, normal ALK receptor in the genesis of other malignancies – including glioblastoma and breast cancer – via a mechanism of receptor activation involving autocrine and/or paracrine growth loops with the reported ALK ligands, pleiotrophin and midkine. This review summarizes normal ALK biology, the confirmed and putative roles of ALK in the development of human cancers and efforts to target ALK using small-molecule kinase inhibitors. PMID:19275511

Low Piconewton Towing of CNS Axons against Diffusing and Surface-Bound Repellents Requires the Inhibition of Motor Protein-Associated Pathways

NASA Astrophysics Data System (ADS)

Kilinc, Devrim; Blasiak, Agata; O'Mahony, James J.; Lee, Gil U.

2014-11-01

Growth cones, dynamic structures at axon tips, integrate chemical and physical stimuli and translate them into coordinated axon behaviour, e.g., elongation or turning. External force application to growth cones directs and enhances axon elongation in vitro; however, direct mechanical stimulation is rarely combined with chemotactic stimulation. We describe a microfluidic device that exposes isolated cortical axons to gradients of diffusing and substrate-bound molecules, and permits the simultaneous application of piconewton (pN) forces to multiple individual growth cones via magnetic tweezers. Axons treated with Y-27632, a RhoA kinase inhibitor, were successfully towed against Semaphorin 3A gradients, which repel untreated axons, with less than 12 pN acting on a small number of neural cell adhesion molecules. Treatment with Y-27632 or monastrol, a kinesin-5 inhibitor, promoted axon towing on substrates coated with chondroitin sulfate proteoglycans, potent axon repellents. Thus, modulating key molecular pathways that regulate contractile stress generation in axons counteracts the effects of repellent molecules and promotes tension-induced growth. The demonstration of parallel towing of axons towards inhibitory environments with minute forces suggests that mechanochemical stimulation may be a promising therapeutic approach for the repair of the damaged central nervous system, where regenerating axons face repellent factors over-expressed in the glial scar.

Impact of cholesterol on voids in phospholipid membranes

NASA Astrophysics Data System (ADS)

Falck, Emma; Patra, Michael; Karttunen, Mikko; Hyvönen, Marja T.; Vattulainen, Ilpo

2004-12-01

Free volume pockets or voids are important to many biological processes in cell membranes. Free volume fluctuations are a prerequisite for diffusion of lipids and other macromolecules in lipid bilayers. Permeation of small solutes across a membrane, as well as diffusion of solutes in the membrane interior are further examples of phenomena where voids and their properties play a central role. Cholesterol has been suggested to change the structure and function of membranes by altering their free volume properties. We study the effect of cholesterol on the properties of voids in dipalmitoylphosphatidylcholine (DPPC) bilayers by means of atomistic molecular dynamics simulations. We find that an increasing cholesterol concentration reduces the total amount of free volume in a bilayer. The effect of cholesterol on individual voids is most prominent in the region where the steroid ring structures of cholesterol molecules are located. Here a growing cholesterol content reduces the number of voids, completely removing voids of the size of a cholesterol molecule. The voids also become more elongated. The broad orientational distribution of voids observed in pure DPPC is, with a 30% molar concentration of cholesterol, replaced by a distribution where orientation along the bilayer normal is favored. Our results suggest that instead of being uniformly distributed to the whole bilayer, these effects are localized to the close vicinity of cholesterol molecules.

A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery.

PubMed

Fine, Daniel; Grattoni, Alessandro; Hosali, Sharath; Ziemys, Arturas; De Rosa, Enrica; Gill, Jaskaran; Medema, Ryan; Hudson, Lee; Kojic, Milos; Milosevic, Miljan; Brousseau Iii, Louis; Goodall, Randy; Ferrari, Mauro; Liu, Xuewu

2010-11-21

This manuscript demonstrates a mechanically robust implantable nanofluidic membrane capable of tunable long-term zero-order release of therapeutic agents in ranges relevant for clinical applications. The membrane, with nanochannels as small as 5 nm, allows for the independent control of both dosage and mechanical strength through the integration of high-density short nanochannels parallel to the membrane surface with perpendicular micro- and macrochannels for interfacing with the ambient solutions. These nanofluidic membranes are created using precision silicon fabrication techniques on silicon-on-insulator substrates enabling exquisite control over the monodispersed nanochannel dimensions and surface roughness. Zero-order release of analytes is achieved by exploiting molecule to surface interactions which dominate diffusive transport when fluids are confined to the nanoscale. In this study we investigate the nanofluidic membrane performance using custom diffusion and gas testing apparatuses to quantify molecular release rate and process uniformity as well as mechanical strength using a gas based burst test. The kinetics of the constrained zero-order release is probed with molecules presenting a range of sizes, charge states, and structural conformations. Finally, an optimal ratio of the molecular hydrodynamic diameter to the nanochannel dimension is determined to assure zero-order release for each tested molecule.

Investigation of the dynamics of aqueous proline solutions using neutron scattering and molecular dynamics simulations.

PubMed

Malo de Molina, Paula; Alvarez, Fernando; Frick, Bernhard; Wildes, Andrew; Arbe, Arantxa; Colmenero, Juan

2017-10-18

We applied quasielastic neutron scattering (QENS) techniques to samples with two different contrasts (deuterated solute/hydrogenated solvent and the opposite label) to selectively study the component dynamics of proline/water solutions. Results on diluted and concentrated solutions (31 and 6 water molecules/proline molecule, respectively) were analyzed in terms of the susceptibility and considering a recently proposed model for water dynamics [Arbe et al., Phys. Rev. Lett., 2016, 117, 185501] which includes vibrations and the convolution of localized motions and diffusion. We found that proline molecules not only reduce the average diffusion coefficient of water but also extend the time/frequency range of the crossover region ('cage') between the vibrations and purely diffusive behavior. For the high proline concentration we also found experimental evidence of water heterogeneous dynamics and a distribution of diffusion coefficients. Complementary molecular dynamics simulations show that water molecules start to perform rotational diffusion when they escape the cage regime but before the purely diffusive behavior is established. The rotational diffusion regime is also retarded by the presence of proline molecules. On the other hand, a strong coupling between proline and water diffusive dynamics which persists with decreasing temperature is directly observed using QENS. Not only are the temperature dependences of the diffusion coefficients of both components the same, but their absolute values also approach each other with increasing proline concentration. We compared our results with those reported using other techniques, in particular using dielectric spectroscopy (DS). A simple approach based on molecular hydrodynamics and a molecular treatment of DS allows rationalizing the a priori puzzling inconsistency between QENS and dielectric results regarding the dynamic coupling of the two components. The interpretation proposed is based on general grounds and therefore should be applicable to other biomolecular solutions.

Temperature dependence of water diffusion pools in brain white matter.

PubMed

Dhital, Bibek; Labadie, Christian; Stallmach, Frank; Möller, Harald E; Turner, Robert

2016-02-15

Water diffusion in brain tissue can now be easily investigated using magnetic resonance (MR) techniques, providing unique insights into cellular level microstructure such as axonal orientation. The diffusive motion in white matter is known to be non-Gaussian, with increasing evidence for more than one water-containing tissue compartment. In this study, freshly excised porcine brain white matter was measured using a 125-MHz MR spectrometer (3T) equipped with gradient coils providing magnetic field gradients of up to 35,000 mT/m. The sample temperature was varied between -14 and +19 °C. The hypothesis tested was that white matter contains two slowly exchanging pools of water molecules with different diffusion properties. A Stejskal-Tanner diffusion sequence with very short gradient pulses and b-factors up to 18.8 ms/μm(2) was used. The dependence on b-factor of the attenuation due to diffusion was robustly fitted by a biexponential function, with comparable volume fractions for each component. The diffusion coefficient of each component follows Arrhenius behavior, with significantly different activation energies. The measured volume fractions are consistent with the existence of three water-containing compartments, the first comprising relatively free cytoplasmic and extracellular water molecules, the second of water molecules in glial processes, and the third comprising water molecules closely associated with membranes, as for example, in the myelin sheaths and elsewhere. The activation energy of the slow diffusion pool suggests proton hopping at the surface of membranes by a Grotthuss mechanism, mediated by hydrating water molecules. Copyright © 2015 Elsevier Inc. All rights reserved.

Probing Biological Processes on Supported Lipid Bilayers with Single-Walled Carbon Nanotube Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Zhou, Xinjian; Moran-Mirabal, Jose Manuel; Craighead, Harold; McEuen, Paul

2006-03-01

We have formed supported lipid bilayers (SLBs) by small unilamellar vesicle fusion on substrates containing single-walled carbon nanotube field-effect transistors (SWNT-FETs). We are able to detect the self-assembly of SLBs electrically with SWNT-FETs since their threshold voltages are shifted by this event. The SLB fully covers the NT surface and lipid molecules can diffuse freely in the bilayer surface across the NT. To study the interactions of important biological entities with receptors imbedded within the membrane, we have also integrated a membrane protein, GT1b ganglioside, in the bilayer. While bare gangliosides can diffuse freely across the NT, interestingly the NT acts as a diffusion barrier for the gangliosides when they are bound with tetanus toxin. This experiment opens the possibility of using SWNT-FETs as biosensors for label-free detection.

Confronting Practical Problems for Initiation of On-line Hemodiafiltration Therapy.

PubMed

Kim, Yang Wook; Park, Sihyung

2016-06-01

Conventional hemodialysis, which is based on the diffusive transport of solutes, is the most widely used renal replacement therapy. It effectively removes small solutes such as urea and corrects fluid, electrolyte and acid-base imbalance. However, solute diffusion coefficients decreased rapidly as molecular size increased. Because of this, middle and large molecules are not removed effectively and clinical problem such as dialysis amyloidosis might occur. Online hemodiafiltration which is combined by diffusive and convective therapies can overcome such problems by removing effectively middle and large solutes. Online hemodiafiltration is safe, very effective, economically affordable, improving session tolerance and may improve the mortality superior to high flux hemodialysis. However, there might be some potential limitations for setting up online hemodiafiltaration. In this article, we review the uremic toxins associated with dialysis, definition of hemodiafiltration, indication and prescription of hemodiafiltration and the limitations of setting up hemodiafiltration.

Robust stochastic Turing patterns in the development of a one-dimensional cyanobacterial organism.

PubMed

Di Patti, Francesca; Lavacchi, Laura; Arbel-Goren, Rinat; Schein-Lubomirsky, Leora; Fanelli, Duccio; Stavans, Joel

2018-05-01

Under nitrogen deprivation, the one-dimensional cyanobacterial organism Anabaena sp. PCC 7120 develops patterns of single, nitrogen-fixing cells separated by nearly regular intervals of photosynthetic vegetative cells. We study a minimal, stochastic model of developmental patterns in Anabaena that includes a nondiffusing activator, two diffusing inhibitor morphogens, demographic fluctuations in the number of morphogen molecules, and filament growth. By tracking developing filaments, we provide experimental evidence for different spatiotemporal roles of the two inhibitors during pattern maintenance and for small molecular copy numbers, justifying a stochastic approach. In the deterministic limit, the model yields Turing patterns within a region of parameter space that shrinks markedly as the inhibitor diffusivities become equal. Transient, noise-driven, stochastic Turing patterns are produced outside this region, which can then be fixed by downstream genetic commitment pathways, dramatically enhancing the robustness of pattern formation, also in the biologically relevant situation in which the inhibitors' diffusivities may be comparable.

Accurate reaction-diffusion operator splitting on tetrahedral meshes for parallel stochastic molecular simulations

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

Hepburn, I.; De Schutter, E., E-mail: erik@oist.jp; Theoretical Neurobiology & Neuroengineering, University of Antwerp, Antwerp 2610

Spatial stochastic molecular simulations in biology are limited by the intense computation required to track molecules in space either in a discrete time or discrete space framework, which has led to the development of parallel methods that can take advantage of the power of modern supercomputers in recent years. We systematically test suggested components of stochastic reaction-diffusion operator splitting in the literature and discuss their effects on accuracy. We introduce an operator splitting implementation for irregular meshes that enhances accuracy with minimal performance cost. We test a range of models in small-scale MPI simulations from simple diffusion models to realisticmore » biological models and find that multi-dimensional geometry partitioning is an important consideration for optimum performance. We demonstrate performance gains of 1-3 orders of magnitude in the parallel implementation, with peak performance strongly dependent on model specification.« less

Fluid flow and convective transport of solutes within the intervertebral disc.

PubMed

Ferguson, Stephen J; Ito, Keita; Nolte, Lutz P

2004-02-01

Previous experimental and analytical studies of solute transport in the intervertebral disc have demonstrated that for small molecules diffusive transport alone fulfils the nutritional needs of disc cells. It has been often suggested that fluid flow into and within the disc may enhance the transport of larger molecules. The goal of the study was to predict the influence of load-induced interstitial fluid flow on mass transport in the intervertebral disc. An iterative procedure was used to predict the convective transport of physiologically relevant molecules within the disc. An axisymmetric, poroelastic finite-element structural model of the disc was developed. The diurnal loading was divided into discrete time steps. At each time step, the fluid flow within the disc due to compression or swelling was calculated. A sequentially coupled diffusion/convection model was then employed to calculate solute transport, with a constant concentration of solute being provided at the vascularised endplates and outer annulus. Loading was simulated for a complete diurnal cycle, and the relative convective and diffusive transport was compared for solutes with molecular weights ranging from 400 Da to 40 kDa. Consistent with previous studies, fluid flow did not enhance the transport of low-weight solutes. During swelling, interstitial fluid flow increased the unidirectional penetration of large solutes by approximately 100%. Due to the bi-directional temporal nature of disc loading, however, the net effect of convective transport over a full diurnal cycle was more limited (30% increase). Further study is required to determine the significance of large solutes and the timing of their delivery for disc physiology.

Structural basis for the selective permeability of channels made of communicating junction proteins

PubMed Central

Ek-Vitorin, Jose F.; Burt, Janis M.

2012-01-01

The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore’s limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. PMID:22342665

Molecular Effects of Concentrated Solutes on Protein Hydration, Dynamics, and Electrostatics.

PubMed

Abriata, Luciano A; Spiga, Enrico; Peraro, Matteo Dal

2016-08-23

Most studies of protein structure and function are performed in dilute conditions, but proteins typically experience high solute concentrations in their physiological scenarios and biotechnological applications. High solute concentrations have well-known effects on coarse protein traits like stability, diffusion, and shape, but likely also perturb other traits through finer effects pertinent at the residue and atomic levels. Here, NMR and molecular dynamics investigations on ubiquitin disclose variable interactions with concentrated solutes that lead to localized perturbations of the protein's surface, hydration, electrostatics, and dynamics, all dependent on solute size and chemical properties. Most strikingly, small polar uncharged molecules are sticky on the protein surface, whereas charged small molecules are not, but the latter still perturb the internal protein electrostatics as they diffuse nearby. Meanwhile, interactions with macromolecular crowders are favored mainly through hydrophobic, but not through polar, surface patches. All the tested small solutes strongly slow down water exchange at the protein surface, whereas macromolecular crowders do not exert such strong perturbation. Finally, molecular dynamics simulations predict that unspecific interactions slow down microsecond- to millisecond-timescale protein dynamics despite having only mild effects on pico- to nanosecond fluctuations as corroborated by NMR. We discuss our results in the light of recent advances in understanding proteins inside living cells, focusing on the physical chemistry of quinary structure and cellular organization, and we reinforce the idea that proteins should be studied in native-like media to achieve a faithful description of their function. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Predicting the size-dependent tissue accumulation of agents released from vascular targeted nanoconstructs

NASA Astrophysics Data System (ADS)

de Tullio, Marco D.; Singh, Jaykrishna; Pascazio, Giuseppe; Decuzzi, Paolo

2014-03-01

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vessel wall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate , ranging from to ; the wall filtration velocity , varying from to ; and the agent diffusion coefficient , ranging from to . It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate , and with a decrease in filtration velocity and agent diffusivity . In particular, in tumor microvessels, characterized by lower shear rates () and higher filtration velocities (), an agent with a diffusivity (i.e. a 50 nm particle) is predicted to deposit on the vessel wall up to of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (), are predicted to accumulate up to . In healthy vessels, characterized by higher and lower , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.

Microimaging of transient guest profiles to monitor mass transfer in nanoporous materials

NASA Astrophysics Data System (ADS)

Kärger, Jörg; Binder, Tomas; Chmelik, Christian; Hibbe, Florian; Krautscheid, Harald; Krishna, Rajamani; Weitkamp, Jens

2014-04-01

The intense interactions of guest molecules with the pore walls of nanoporous materials is the subject of continued fundamental research. Stimulated by their thermal energy, the guest molecules in these materials are subject to a continuous, irregular motion, referred to as diffusion. Diffusion, which is omnipresent in nature, influences the efficacy of nanoporous materials in reaction and separation processes. The recently introduced techniques of microimaging by interference and infrared microscopy provide us with a wealth of information on diffusion, hitherto inaccessible from commonly used techniques. Examples include the determination of surface barriers and the sticking coefficient's analogue, namely the probability that, on colliding with the particle surface, a molecule may continue its diffusion path into the interior. Microimaging is further seen to open new vistas in multicomponent guest diffusion (including the detection of a reversal in the preferred diffusion pathways), in guest-induced phase transitions in nanoporous materials and in matching the results of diffusion studies under equilibrium and non-equilibrium conditions.

b matrix errors in echo planar diffusion tensor imaging

PubMed Central

Boujraf, Saïd; Luypaert, Robert; Osteaux, Michel

2001-01-01

Diffusion‐weighted magnetic resonance imaging (DW‐MRI) is a recognized tool for early detection of infarction of the human brain. DW‐MRI uses the signal loss associated with the random thermal motion of water molecules in the presence of magnetic field gradients to derive parameters that reflect the translational mobility of the water molecules in tissues. If diffusion‐weighted images with different values of b matrix are acquired during one individual investigation, it is possible to calculate apparent diffusion coefficient maps that are the elements of the diffusion tensor. The diffusion tensor elements represent the apparent diffusion coefficient of protons of water molecules in each pixel in the corresponding sample. The relation between signal intensity in the diffusion‐weighted images, diffusion tensor, and b matrix is derived from the Bloch equations. Our goal is to establish the magnitude of the error made in the calculation of the elements of the diffusion tensor when the imaging gradients are ignored. PACS number(s): 87.57. –s, 87.61.–c PMID:11602015

Nitrogen diffusion in hafnia and the impact of nitridation on oxygen and hydrogen diffusion: A first-principles study

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

Sathiyanarayanan, Rajesh, E-mail: rajessat@in.ibm.com, E-mail: rajesh.sathiyanarayanan@gmail.com; Pandey, R. K.; Murali, K. V. R. M.

2015-01-21

Using first-principles simulations, we have computed incorporation energies and diffusion barriers of ammonia, the nitrogen molecule and atomic nitrogen in monoclinic hafnia (m-HfO{sub 2}). Our calculations show that ammonia is likely to dissociate into an NH{sub 2} molecular unit, whereas the nitrogen molecule remains as a molecule either in the interstitial space or at an oxygen lattice site. The lowest energy pathway for the diffusion of atomic nitrogen interstitials consists of the hopping of the nitrogen interstitial between neighboring three-coordinated lattice oxygen atoms that share a single Hf atom, and the barrier for such hops is determined by a switchingmore » mechanism. The substitutional nitrogen atom shows a preference for diffusion through the doubly positive oxygen vacancy-mediated mechanism. Furthermore, we have investigated the impact of nitrogen atoms on the diffusion barriers of oxygen and hydrogen interstitials in m-HfO{sub 2}. Our results show that nitrogen incorporation has a significant impact on the barriers for oxygen and hydrogen diffusion: nitrogen atoms attract oxygen and hydrogen interstitials diffusing in the vicinity, thereby slowing down (reducing) their diffusion (diffusion length)« less

MSM/RD: Coupling Markov state models of molecular kinetics with reaction-diffusion simulations

NASA Astrophysics Data System (ADS)

Dibak, Manuel; del Razo, Mauricio J.; De Sancho, David; Schütte, Christof; Noé, Frank

2018-06-01

Molecular dynamics (MD) simulations can model the interactions between macromolecules with high spatiotemporal resolution but at a high computational cost. By combining high-throughput MD with Markov state models (MSMs), it is now possible to obtain long time-scale behavior of small to intermediate biomolecules and complexes. To model the interactions of many molecules at large length scales, particle-based reaction-diffusion (RD) simulations are more suitable but lack molecular detail. Thus, coupling MSMs and RD simulations (MSM/RD) would be highly desirable, as they could efficiently produce simulations at large time and length scales, while still conserving the characteristic features of the interactions observed at atomic detail. While such a coupling seems straightforward, fundamental questions are still open: Which definition of MSM states is suitable? Which protocol to merge and split RD particles in an association/dissociation reaction will conserve the correct bimolecular kinetics and thermodynamics? In this paper, we make the first step toward MSM/RD by laying out a general theory of coupling and proposing a first implementation for association/dissociation of a protein with a small ligand (A + B ⇌ C). Applications on a toy model and CO diffusion into the heme cavity of myoglobin are reported.

The Fe(III) and Ga(III) coordination chemistry of 3-(1-hydroxymethylidene) and 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione: Novel tetramic acid degradation products of homoserine lactone bacterial quorum sensing molecules

PubMed Central

Romano, Ariel A.; Hahn, Tobias; Davis, Nicole; Lowery, Colin A.; Struss, Anjali K.; Janda, Kim D.; Böttger, Lars H.; Matzanke, Berthold F.; Carrano, Carl J.

2011-01-01

Bacteria use small diffusible molecules to exchange information in a process called quorum sensing (QS). An important class of quorum sensing molecules used by Gram-negative bacteria is the family of N-acylhomoserine lactones (HSL). It was recently discovered that a degradation product of the QS molecule 3-oxo-C12-homoserine lactone, the tetramic acid 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, is a potent antibacterial agent, thus implying roles for QS outside of simply communication. Because these tetramic acids also appear to bind iron with appreciable affinity it was suggested that metal binding might contribute to their biological activity. Here, using a variety of spectroscopic tools, we describe the coordination chemistry of both the methylidene and decylidene tetramic acid derivatives with Fe(III) and Ga(III) and discuss the potential biological significance of such metal binding. PMID:22178671

Trapping gases in metal-organic frameworks with a selective surface molecular barrier layer

DOE PAGES

Tan, Kui; Zuluaga, Sebastian; Fuentes, Erika; ...

2016-12-13

The main challenge for gas storage and separation in nanoporous materials is that many molecules of interest adsorb too weakly to be effectively retained. Instead of synthetically modifying the internal surface structure of the entire bulk—as is typically done to enhance adsorption—here we show that post exposure of a prototypical porous metal-organic framework to ethylenediamine can effectively retain a variety of weakly adsorbing molecules (for example, CO, CO 2, SO 2, C 2H 4, NO) inside the materials by forming a monolayer-thick cap at the external surface of microcrystals. Furthermore, this capping mechanism, based on hydrogen bonding as explained bymore » ab initio modelling, opens the door for potential selectivity. For example, water molecules are shown to disrupt the hydrogen-bonded amine network and diffuse through the cap without hindrance and fully displace/release the retained small molecules out of the metal-organic framework at room temperature. Lastly, these findings may provide alternative strategies for gas storage, delivery and separation.« less

Single-Molecule Tracking Photoactivated Localization Microscopy to Map Nano-Scale Structure and Dynamics in Living Spines

PubMed Central

MacGillavry, Harold D.; Blanpied, Thomas A.

2013-01-01

Super-resolution microscopy has rapidly become an indispensable tool in cell biology and neuroscience by enabling measurement in live cells of structures smaller than the classical limit imposed by diffraction. The most widely applied super-resolution method currently is localization microscopy, which takes advantage of the ability to determine the position of individual fluorescent molecules with nanometer accuracy even in cells. By iteratively measuring sparse subsets of photoactivatable fluorescent proteins, protein distribution in macromolecular structures can be accurately reconstructed. Moreover, the motion trajectories of individual molecules within cells can be measured, providing unique ability to measure transport kinetics, exchange rates, and binding affinities of even small subsets of molecules with high temporal resolution and great spatial specificity. This unit describes protocols to measure and quantify the distribution of scaffold proteins within single synapses of cultured hippocampal neurons, and to track and measure the diffusion of intracellular constituents of the neuronal plasma membrane. PMID:25429311

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

Bu, Lintao; Nimlos, Mark R.; Robichaud, David J.

Hierarchical mesoporous zeolites exhibit higher catalytic activities and longer lifetime compared to the traditional microporous zeolites due to improved diffusivity of substrate molecules and their enhanced access to the zeolite active sites. Understanding diffusion of biomass pyrolysis vapors and their upgraded products in such materials is fundamentally important during catalytic fast pyrolysis (CFP) of lignocellulosic biomass, since diffusion makes major contribution to determine shape selectivity and product distribution. However, diffusivities of biomass relevant species in hierarchical mesoporous zeolites are poorly characterized, primarily due to the limitations of the available experimental technology. In this work, molecular dynamics (MD) simulations are utilizedmore » to investigate the diffusivities of several selected coke precursor molecules, benzene, naphthalene, and anthracene, in hierarchical mesoporous H-ZSM-5 zeolite. The effects of temperature and size of mesopores on the diffusivity of the chosen model compounds are examined. The simulation results demonstrate that diffusion within the microspores as well as on the external surface of mesoporous H-ZSM-5 dominates only at low temperature. At pyrolysis relevant temperatures, mass transfer is essentially conducted via diffusion along the mesopores. Additionally, the results illustrate the heuristic diffusion model, such as the extensively used Knudsen diffusion, overestimates the diffusion of bulky molecules in the mesopores, thus making MD simulation a powerful and compulsory approach to explore diffusion in zeolites.« less

Property evaluations and application for separation of small molecules of a nanodiamond-polymer composite monolithic column.

PubMed

Wang, Fengqing; Wei, Aile; Wang, Xixi; Liu, Haiyan; Bai, Ligai; Yan, Hongyuan

2016-07-01

A nanodiamond-polymer composite monolithic column was first prepared successfully with modified nanodiamond (ND) as monomer, ethylene glycol dimethacrylate (EDMA) as cross-linker, 1-dodecanol as porogenic agent and benzoyl peroxide/dimethylacetamide (BPO/DMA) as initiator at 35°C for 2.5h. There was a sharp increase of specific surface area with ND added about 22 times from 0mg (3.90m(2)/g) to 7mg (81.2m(2)/g) determined with BET. Characterizations including scanning electron microscopy (SEM), fourier-transform infrared spectra (FIRT) and mercury intrusion porosimetry (MIP) were used to determine the microstructure, group composition, pore size distribution (≃1.56μm) and porosity (≃0.7484μm) of the monolith. An excellent column stability was confirmed by permeability (1.258x10(-10)cm(2)) and good linearity (R(2)=0.998) corresponding to backpressures measured at different flow rates. The highest swelling ability of the composite was about (5%) and classical RPLC of the column obtained occurred with the acetonitrile concentration increasing from 20% to 85% in the mobile phase, above which another retention model of normal-phase chromatography appeared. The items of the eddy dispersion and the absorption-release kinetics were the decisional factors of the composite column compared with the factors of longitudinal diffusion, and the skeleton-eluent mass transfer resistance due to the finite diffusivity. Good separation of neutral and basic small molecules was obtained (24,350 plates/m for neutral molecules and 22,300 plates/m for basic ones) with the hydrophobicity retention mechanism, but not for the acidic ones except to regulate the pH of the mobile phase. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy.

PubMed

Ugaonkar, Shweta R; Wesenberg, Asa; Wilk, Jolanta; Seidor, Samantha; Mizenina, Olga; Kizima, Larisa; Rodriguez, Aixa; Zhang, Shimin; Levendosky, Keith; Kenney, Jessica; Aravantinou, Meropi; Derby, Nina; Grasperge, Brooke; Gettie, Agegnehu; Blanchard, James; Kumar, Narender; Roberts, Kevin; Robbiani, Melissa; Fernández-Romero, José A; Zydowsky, Thomas M

2015-09-10

Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased risk of HIV-1 acquisition) and prevents unintended pregnancy. Here, we describe a novel core-matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered the MZC combination microbicide and a contraceptive. The MZCL IVR contains four active pharmaceutical ingredients (APIs): MIV-150 (targets HIV-1), zinc acetate (ZA; targets HIV-1 and HSV-2), carrageenan (CG; targets HPV and HSV-2), and levonorgestrel (LNG; targets unintended pregnancy). The elastomeric IVR body (matrix) was produced by hot melt extrusion of the non-water swellable elastomer, ethylene vinyl acetate (EVA-28), containing the hydrophobic small molecules, MIV-150 and LNG. The solid hydrophilic core, embedded within the IVR by compression, contained the small molecule ZA and the macromolecule CG. Hydrated ZA/CG from the core was released by diffusion via a pore on the IVR while the MIV-150/LNG diffused from the matrix continuously for 94 days (d) in vitro and up to 28 d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1ADA-M, HSV-2, and HPV16 PsV in cell-based assays. Serum LNG was at levels associated with local contraceptive effects. The results demonstrate proof-of-concept of a novel core-matrix IVR for sustained and simultaneous delivery of diverse molecules for the prevention of HIV, HSV-2 and HPV acquisition, as well as unintended pregnancy. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Time scale of random sequential adsorption.

PubMed

Erban, Radek; Chapman, S Jonathan

2007-04-01

A simple multiscale approach to the diffusion-driven adsorption from a solution to a solid surface is presented. The model combines two important features of the adsorption process: (i) The kinetics of the chemical reaction between adsorbing molecules and the surface and (ii) geometrical constraints on the surface made by molecules which are already adsorbed. The process (i) is modeled in a diffusion-driven context, i.e., the conditional probability of adsorbing a molecule provided that the molecule hits the surface is related to the macroscopic surface reaction rate. The geometrical constraint (ii) is modeled using random sequential adsorption (RSA), which is the sequential addition of molecules at random positions on a surface; one attempt to attach a molecule is made per one RSA simulation time step. By coupling RSA with the diffusion of molecules in the solution above the surface the RSA simulation time step is related to the real physical time. The method is illustrated on a model of chemisorption of reactive polymers to a virus surface.

Conserved linear dynamics of single-molecule Brownian motion.

PubMed

Serag, Maged F; Habuchi, Satoshi

2017-06-06

Macromolecular diffusion in homogeneous fluid at length scales greater than the size of the molecule is regarded as a random process. The mean-squared displacement (MSD) of molecules in this regime increases linearly with time. Here we show that non-random motion of DNA molecules in this regime that is undetectable by the MSD analysis can be quantified by characterizing the molecular motion relative to a latticed frame of reference. Our lattice occupancy analysis reveals unexpected sub-modes of motion of DNA that deviate from expected random motion in the linear, diffusive regime. We demonstrate that a subtle interplay between these sub-modes causes the overall diffusive motion of DNA to appear to conform to the linear regime. Our results show that apparently random motion of macromolecules could be governed by non-random dynamics that are detectable only by their relative motion. Our analytical approach should advance broad understanding of diffusion processes of fundamental relevance.

Conserved linear dynamics of single-molecule Brownian motion

PubMed Central

Serag, Maged F.; Habuchi, Satoshi

2017-01-01

Macromolecular diffusion in homogeneous fluid at length scales greater than the size of the molecule is regarded as a random process. The mean-squared displacement (MSD) of molecules in this regime increases linearly with time. Here we show that non-random motion of DNA molecules in this regime that is undetectable by the MSD analysis can be quantified by characterizing the molecular motion relative to a latticed frame of reference. Our lattice occupancy analysis reveals unexpected sub-modes of motion of DNA that deviate from expected random motion in the linear, diffusive regime. We demonstrate that a subtle interplay between these sub-modes causes the overall diffusive motion of DNA to appear to conform to the linear regime. Our results show that apparently random motion of macromolecules could be governed by non-random dynamics that are detectable only by their relative motion. Our analytical approach should advance broad understanding of diffusion processes of fundamental relevance. PMID:28585925

Conserved linear dynamics of single-molecule Brownian motion

NASA Astrophysics Data System (ADS)

Serag, Maged F.; Habuchi, Satoshi

2017-06-01

Macromolecular diffusion in homogeneous fluid at length scales greater than the size of the molecule is regarded as a random process. The mean-squared displacement (MSD) of molecules in this regime increases linearly with time. Here we show that non-random motion of DNA molecules in this regime that is undetectable by the MSD analysis can be quantified by characterizing the molecular motion relative to a latticed frame of reference. Our lattice occupancy analysis reveals unexpected sub-modes of motion of DNA that deviate from expected random motion in the linear, diffusive regime. We demonstrate that a subtle interplay between these sub-modes causes the overall diffusive motion of DNA to appear to conform to the linear regime. Our results show that apparently random motion of macromolecules could be governed by non-random dynamics that are detectable only by their relative motion. Our analytical approach should advance broad understanding of diffusion processes of fundamental relevance.

New insights in dehydration stress behavior of two maize hybrids using advanced distributed reactivity model (DRM). Responses to the impact of 24-epibrassinolide

PubMed Central

Janković, Bojan; Janković, Marija; Nikolić, Bogdan; Dimkić, Ivica; Lalević, Blažo; Raičević, Vera

2017-01-01

Proposed distributed reactivity model of dehydration for seedling parts of two various maize hybrids (ZP434, ZP704) was established. Dehydration stresses were induced thermally, which is also accompanied by response of hybrids to heat stress. It was found that an increased value of activation energy counterparts within radicle dehydration of ZP434, with a high concentration of 24-epibrassinolide (24-EBL) at elevated operating temperatures, probably causes activation of diffusion mechanisms in cutin network and may increases likelihood of formation of free volumes, large enough to accommodate diffusing molecule. Many small random effects were detected and can be correlated with micro-disturbing in a space filled with water caused by thermal gradients, increasing capillary phenomena, and which can induce thermo-capillary migration. The influence of seedling content of various sugars and minerals on dehydration was also examined. Estimated distributed reactivity models indicate a dependence of reactivity on structural arrangements, due to present interactions between water molecules and chemical species within the plant. PMID:28644899

The influence of trehalose on hydrophobic interactions of small nonpolar solute: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Paul, Subrata; Paul, Sandip

2013-07-01

Molecular dynamics simulations were carried out to investigate the influences of aqueous trehalose solution on the hydrophobic interactions between neopentane molecules. In this study, we consider six different trehalose concentrations ranging from 0% to 56%. We observe that with increasing trehalose concentration the dispersion of solute neopentane takes place. The neopentane-neopentane association constant value decreases with addition of trehalose. Our preferential interaction calculations suggest that with increasing trehalose concentration neopentane interacts preferentially with water over trehalose. Site-site neopentane-trehalose rdfs indicate that trehalose molecules are expelled out from the neopentane surface. Also observed are (i) trehalose induced second shell collapse of water network (ii) decrease in average number of water-water and water-trehalose hydrogen bonds with increasing trehalose concentration. We also find that addition of trehalose decreases the translational motion of all the solution species. The decrease in diffusion coefficient value is more pronounced for trehalose. We, further, observe that the ratio of the diffusion coefficient values of water and trehalose increases with increasing trehalose concentration.

New insights in dehydration stress behavior of two maize hybrids using advanced distributed reactivity model (DRM). Responses to the impact of 24-epibrassinolide.

PubMed

Waisi, Hadi; Janković, Bojan; Janković, Marija; Nikolić, Bogdan; Dimkić, Ivica; Lalević, Blažo; Raičević, Vera

2017-01-01

Proposed distributed reactivity model of dehydration for seedling parts of two various maize hybrids (ZP434, ZP704) was established. Dehydration stresses were induced thermally, which is also accompanied by response of hybrids to heat stress. It was found that an increased value of activation energy counterparts within radicle dehydration of ZP434, with a high concentration of 24-epibrassinolide (24-EBL) at elevated operating temperatures, probably causes activation of diffusion mechanisms in cutin network and may increases likelihood of formation of free volumes, large enough to accommodate diffusing molecule. Many small random effects were detected and can be correlated with micro-disturbing in a space filled with water caused by thermal gradients, increasing capillary phenomena, and which can induce thermo-capillary migration. The influence of seedling content of various sugars and minerals on dehydration was also examined. Estimated distributed reactivity models indicate a dependence of reactivity on structural arrangements, due to present interactions between water molecules and chemical species within the plant.

Macromolecular Crowding Regulates the Gene Expression Profile by Limiting Diffusion

DOE PAGES

Golkaram, Mahdi; Hellander, Stefan; Drawert, Brian; ...

2016-11-28

We seek to elucidate the role of macromolecular crowding in transcription and translation. It is well known that stochasticity in gene expression can lead to differential gene expression and heterogeneity in a cell population. Recent experimental observations by Tan et al. have improved our understanding of the functional role of macromolecular crowding. It can be inferred from their observations that macromolecular crowding can lead to robustness in gene expression, resulting in a more homogeneous cell population. We introduce a spatial stochastic model to provide insight into this process. Our results show that macromolecular crowding reduces noise (as measured by themore » kurtosis of the mRNA distribution) in a cell population by limiting the diffusion of transcription factors (i.e. removing the unstable intermediate states), and that crowding by large molecules reduces noise more efficiently than crowding by small molecules. Finally, our simulation results provide evidence that the local variation in chromatin density as well as the total volume exclusion of the chromatin in the nucleus can induce a homogenous cell population« less

Possible influence of the Kuramoto length in a photo-catalytic water splitting reaction revealed by Poisson-Nernst-Planck equations involving ionization in a weak electrolyte

NASA Astrophysics Data System (ADS)

Suzuki, Yohichi; Seki, Kazuhiko

2018-03-01

We studied ion concentration profiles and the charge density gradient caused by electrode reactions in weak electrolytes by using the Poisson-Nernst-Planck equations without assuming charge neutrality. In weak electrolytes, only a small fraction of molecules is ionized in bulk. Ion concentration profiles depend on not only ion transport but also the ionization of molecules. We considered the ionization of molecules and ion association in weak electrolytes and obtained analytical expressions for ion densities, electrostatic potential profiles, and ion currents. We found the case that the total ion density gradient was given by the Kuramoto length which characterized the distance over which an ion diffuses before association. The charge density gradient is characterized by the Debye length for 1:1 weak electrolytes. We discuss the role of these length scales for efficient water splitting reactions using photo-electrocatalytic electrodes.

Translational diffusion of cumene and 3-methylpentane on free surfaces and pore walls studied by time-of-flight secondary ion mass spectrometry

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

Souda, Ryutaro

2010-12-07

Mobility of molecules in confined geometry has been studied extensively, but the origins of finite size effects on reduction of the glass transition temperature, T{sub g}, are controversial especially for supported thin films. We investigate uptake of probe molecules in vapor-deposited thin films of cumene, 3-methylpentane, and heavy water using secondary ion mass spectrometry and discuss roles of individual molecular motion during structural relaxation and glass-liquid transition. The surface mobility is found to be enhanced for low-density glasses in the sub-T{sub g} region because of the diffusion of molecules on pore walls, resulting in densification of a film via poremore » collapse. Even for high-density glasses without pores, self-diffusion commences prior to the film morphology change at T{sub g}, which is thought to be related to decoupling between translational diffusivity and viscosity. The diffusivity of deeply supercooled liquid tends to be enhanced when it is confined in pores of amorphous solid water. The diffusivity of molecules is further enhanced at temperatures higher than 1.2-1.3 T{sub g} irrespective of the confinement.« less

Control of the photosynthetic electron transport by PQ diffusion microdomains in thylakoids of higher plants.

PubMed

Kirchhoff, H; Horstmann, S; Weis, E

2000-07-20

We investigate the role of plastoquinone (PQ) diffusion in the control of the photosynthetic electron transport. A control analysis reveals an unexpected flux control of the whole chain electron transport by photosystem (PS) II. The contribution of PSII to the flux control of whole chain electron transport was high in stacked thylakoids (control coefficient, CJ(PSII) =0.85), but decreased after destacking (CJ(PSII)=0.25). From an 'electron storage' experiment, we conclude that in stacked thylakoids only about 50 to 60% of photoreducable PQ is involved in the light-saturated linear electron transport. No redox equilibration throughout the membrane between fixed redox groups at PSII and cytochrome (cyt) bf complexes, and the diffusable carrier PQ is achieved. The data support the PQ diffusion microdomain concept by Lavergne et al. [J. Lavergne, J.-P. Bouchaud, P. Joliot, Biochim. Biophys. Acta 1101 (1992) 13-22], but we come to different conclusions about size, structure and size distribution of domains. From an analysis of cyt b6 reduction, as a function of PSII inhibition, we conclude that in stacked thylakoids about 70% of PSII is located in small domains, where only 1 to 2 PSII share a local pool of a few PQ molecules. Thirty percent of PSII is located in larger domains. No small domains were found in destacked thylakoids. We present a structural model assuming a hierarchy of specific, strong and weak interactions between PSII core, light harvesting complexes (LHC) II and cyt bf. Peripheral LHCII's may serve to connect PSII-LHCII supercomplexes to a flexible protein network, by which small closed lipid diffusion compartments are formed. Within each domain, PQ moves rapidly and shuttles electrons between PSII and cyt bf complexes in the close vicinity. At the same time, long range diffusion is slow. We conclude, that in high light, cyt bfcomplexes located in distant stromal lamellae (20 to 30%) are not involved in the linear electron transport.

Diffusion of aromatic hydrocarbons in hierarchical mesoporous H-ZSM-5 zeolite

DOE PAGES

Bu, Lintao; Nimlos, Mark R.; Robichaud, David J.; ...

2018-02-08

Hierarchical mesoporous zeolites exhibit higher catalytic activities and longer lifetime compared to the traditional microporous zeolites due to improved diffusivity of substrate molecules and their enhanced access to the zeolite active sites. Understanding diffusion of biomass pyrolysis vapors and their upgraded products in such materials is fundamentally important during catalytic fast pyrolysis (CFP) of lignocellulosic biomass, since diffusion makes major contribution to determine shape selectivity and product distribution. However, diffusivities of biomass relevant species in hierarchical mesoporous zeolites are poorly characterized, primarily due to the limitations of the available experimental technology. In this work, molecular dynamics (MD) simulations are utilizedmore » to investigate the diffusivities of several selected coke precursor molecules, benzene, naphthalene, and anthracene, in hierarchical mesoporous H-ZSM-5 zeolite. The effects of temperature and size of mesopores on the diffusivity of the chosen model compounds are examined. The simulation results demonstrate that diffusion within the microspores as well as on the external surface of mesoporous H-ZSM-5 dominates only at low temperature. At pyrolysis relevant temperatures, mass transfer is essentially conducted via diffusion along the mesopores. Additionally, the results illustrate the heuristic diffusion model, such as the extensively used Knudsen diffusion, overestimates the diffusion of bulky molecules in the mesopores, thus making MD simulation a powerful and compulsory approach to explore diffusion in zeolites.« less

Single-Molecule Detection in Micron-Sized Capillaries

NASA Astrophysics Data System (ADS)

Ball, David A.; Shen, Guoqing; Davis, Lloyd M.

2004-11-01

The detection of individual molecules in solution by laser-induced fluorescence is becoming an increasingly important tool for biophysics research and biotechnology applications. In a typical single-molecule detection (SMD) experiment, diffusion is the dominant mode of transport of fluorophores through the focused laser beam. In order to more rapidly process a large number of slowly diffusing bio-molecules for applications in pharmaceutical drug discovery, a flow can be introduced within a capillary. If the flow speed is sufficient, bio-molecules will be carried through the probe volume significantly faster than by diffusion alone. Here we discuss SMD near the tip of, and in, such micron-sized capillaries, with a high numerical-aperture microscope objective used for confocal-epi-illumination along the axis of the capillary. Problems such as molecular adsorption to the glass are also addressed.

Active-Site Hydration and Water Diffusion in Cytochrome P450cam: A Highly Dynamic Process

PubMed Central

Miao, Yinglong; Baudry, Jerome

2011-01-01

Long-timescale molecular dynamics simulations (300 ns) are performed on both the apo- (i.e., camphor-free) and camphor-bound cytochrome P450cam (CYP101). Water diffusion into and out of the protein active site is observed without biased sampling methods. During the course of the molecular dynamics simulation, an average of 6.4 water molecules is observed in the camphor-binding site of the apo form, compared to zero water molecules in the binding site of the substrate-bound form, in agreement with the number of water molecules observed in crystal structures of the same species. However, as many as 12 water molecules can be present at a given time in the camphor-binding region of the active site in the case of apo-P450cam, revealing a highly dynamic process for hydration of the protein active site, with water molecules exchanging rapidly with the bulk solvent. Water molecules are also found to exchange locations frequently inside the active site, preferentially clustering in regions surrounding the water molecules observed in the crystal structure. Potential-of-mean-force calculations identify thermodynamically favored trans-protein pathways for the diffusion of water molecules between the protein active site and the bulk solvent. Binding of camphor in the active site modifies the free-energy landscape of P450cam channels toward favoring the diffusion of water molecules out of the protein active site. PMID:21943431

Random walk on a leash: a simple single-molecule diffusion model for surface-tethered redox molecules with flexible linkers.

PubMed

Huang, Kuan-Chun; White, Ryan J

2013-08-28

We develop a random walk model to simulate the Brownian motion and the electrochemical response of a single molecule confined to an electrode surface via a flexible molecular tether. We use our simple model, which requires no prior knowledge of the physics of the molecular tether, to predict and better understand the voltammetric response of surface-confined redox molecules when motion of the redox molecule becomes important. The single molecule is confined to a hemispherical volume with a maximum radius determined by the flexible molecular tether (5-20 nm) and is allowed to undergo true three-dimensional diffusion. Distance- and potential-dependent electron transfer probabilities are evaluated throughout the simulations to generate cyclic voltammograms of the model system. We find that at sufficiently slow cyclic voltammetric scan rates the electrochemical reaction behaves like an adsorbed redox molecule with no mass transfer limitation; thus, the peak current is proportional to the scan rate. Conversely, at faster scan rates the diffusional motion of the molecule limits the simulated peak current, which exhibits a linear dependence on the square root of the scan rate. The switch between these two limiting regimes occurs when the diffusion layer thickness, (2Dt)(1/2), is ~10 times the tether length. Finally, we find that our model predicts the voltammetric behavior of a redox-active methylene blue tethered to an electrode surface via short flexible single-stranded, polythymine DNAs, allowing the estimation of diffusion coefficients for the end-tethered molecule.

Transport dynamics -- one particle at a time

NASA Astrophysics Data System (ADS)

Granick, Steve

2010-03-01

By watching particles and molecules diffuse, one-by-one, the full displacement probability distribution can be measured, enabling one to see experimentally how, how fast, and with what fidelity to classical assumptions, particles and molecules diffuse through complex environments. This allows us to measuring the confining tube potential through which thin actin filaments reptate, and also some of the amazing differences in diffusion rate between colloidal particles and phospholipid vesicles of the same size. Pervasively, we find that Brownian diffusion can be non-Gaussian.

Postural variation of pulmonary diffusing capacity as a marker of lung microangiopathy in Indian patients with type 2 diabetes mellitus.

PubMed

Kumar, Avinash; Bade, Geetanjali; Trivedi, Anjali; Jyotsna, Viveka P; Talwar, Anjana

2016-01-01

Diabetes mellitus (DM) is characterized by the presence of chronic hyperglycemia and formation of advanced glycation end products (AGEs). Interaction between AGE and its receptor leads to endothelial damage and microangiopathy. This study was undertaken to investigate the possibility of using a postural variation of diffusing capacity as an early marker of lung microangiopathy and its correlation with the level of adhesion molecules, HbA1c, duration of diabetes, and insulin resistance in type 2 DM (T2DM) patients with and without microangiopathy. Forty patients having T2DM without any microangiopathy (n = 20) as well as with microangiopathy (n = 20), and 22 age and sex matched healthy controls were enrolled in this cross-sectional study. Measurement of lung volumes and capacities were done. DLco was measured in sitting and supine position. Levels of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, fasting glucose, and insulin were estimated in plasma of the patients and compared with controls. Restrictive type of ventilatory change was observed in DM patients. Diffusing capacity (% predicted) in the supine position (P < 0.0001), postural change in DLco (P < 0.0001), and coefficient of diffusion were significantly less in DM patients as compared to controls. Plasma levels of VCAM-1 were significantly higher in DM patients without microangiopathy and negatively correlated (r = -0.4054, P = 0.0094) with Δ DLco in all diabetic subjects. All patients had significantly higher insulin resistance. Lack of postural increase in diffusing capacity in type 2 diabetic patients along with increased VCAM-1 levels could reflect the presence of an early microangiopathy of the small pulmonary vessels.

Giant Acceleration of Diffusion Observed in a Single-Molecule Experiment on F(1)-ATPase.

PubMed

Hayashi, Ryunosuke; Sasaki, Kazuo; Nakamura, Shuichi; Kudo, Seishi; Inoue, Yuichi; Noji, Hiroyuki; Hayashi, Kumiko

2015-06-19

The giant acceleration (GA) of diffusion is a universal phenomenon predicted by the theoretical analysis given by Reimann et al. [Phys. Rev. Lett. 87, 010602 (2001)]. Here we apply the theory of the GA of diffusion to a single-molecule experiment on a rotary motor protein, F(1), which is a component of F(o)F(1) adenosine triphosphate synthase. We discuss the energetic properties of F(1) and identify a high energy barrier of the rotary potential to be 20k(B)T, with the condition that the adenosine diphosphates are tightly bound to the F(1) catalytic sites. To conclude, the GA of diffusion is useful for measuring energy barriers in nonequilibrium and single-molecule experiments.

Giant Acceleration of Diffusion Observed in a Single-Molecule Experiment on F1-ATPase

NASA Astrophysics Data System (ADS)

Hayashi, Ryunosuke; Sasaki, Kazuo; Nakamura, Shuichi; Kudo, Seishi; Inoue, Yuichi; Noji, Hiroyuki; Hayashi, Kumiko

2015-06-01

The giant acceleration (GA) of diffusion is a universal phenomenon predicted by the theoretical analysis given by Reimann et al. [Phys. Rev. Lett. 87, 010602 (2001)]. Here we apply the theory of the GA of diffusion to a single-molecule experiment on a rotary motor protein, F1 , which is a component of Fo F1 adenosine triphosphate synthase. We discuss the energetic properties of F1 and identify a high energy barrier of the rotary potential to be 20 kBT , with the condition that the adenosine diphosphates are tightly bound to the F1 catalytic sites. To conclude, the GA of diffusion is useful for measuring energy barriers in nonequilibrium and single-molecule experiments.

Integrated circuit-based electrochemical sensor for spatially resolved detection of redox-active metabolites in biofilms.

PubMed

Bellin, Daniel L; Sakhtah, Hassan; Rosenstein, Jacob K; Levine, Peter M; Thimot, Jordan; Emmett, Kevin; Dietrich, Lars E P; Shepard, Kenneth L

2014-01-01

Despite advances in monitoring spatiotemporal expression patterns of genes and proteins with fluorescent probes, direct detection of metabolites and small molecules remains challenging. A technique for spatially resolved detection of small molecules would benefit the study of redox-active metabolites that are produced by microbial biofilms and can affect their development. Here we present an integrated circuit-based electrochemical sensing platform featuring an array of working electrodes and parallel potentiostat channels. 'Images' over a 3.25 × 0.9 mm(2) area can be captured with a diffusion-limited spatial resolution of 750 μm. We demonstrate that square wave voltammetry can be used to detect, identify and quantify (for concentrations as low as 2.6 μM) four distinct redox-active metabolites called phenazines. We characterize phenazine production in both wild-type and mutant Pseudomonas aeruginosa PA14 colony biofilms, and find correlations with fluorescent reporter imaging of phenazine biosynthetic gene expression.

Integrated circuit-based electrochemical sensor for spatially resolved detection of redox-active metabolites in biofilms

PubMed Central

Bellin, Daniel L.; Sakhtah, Hassan; Rosenstein, Jacob K.; Levine, Peter M.; Thimot, Jordan; Emmett, Kevin; Dietrich, Lars E. P.; Shepard, Kenneth L.

2014-01-01

Despite advances in monitoring spatiotemporal expression patterns of genes and proteins with fluorescent probes, direct detection of metabolites and small molecules remains challenging. A technique for spatially resolved detection of small molecules would benefit the study of redox-active metabolites produced by microbial biofilms, which can drastically affect colony development. Here we present an integrated circuit-based electrochemical sensing platform featuring an array of working electrodes and parallel potentiostat channels. “Images” over a 3.25 × 0.9 mm area can be captured with a diffusion-limited spatial resolution of 750 μm. We demonstrate that square wave voltammetry can be used to detect, identify, and quantify (for concentrations as low as 2.6 μM) four distinct redox-active metabolites called phenazines. We characterize phenazine production in both wild-type and mutant Pseudomonas aeruginosa PA14 colony biofilms, and find correlations with fluorescent reporter imaging of phenazine biosynthetic gene expression. PMID:24510163

Reducing dynamic disorder in small-molecule organic semiconductors by suppressing large-amplitude thermal motions

PubMed Central

Illig, Steffen; Eggeman, Alexander S.; Troisi, Alessandro; Jiang, Lang; Warwick, Chris; Nikolka, Mark; Schweicher, Guillaume; Yeates, Stephen G.; Henri Geerts, Yves; Anthony, John E.; Sirringhaus, Henning

2016-01-01

Thermal vibrations and the dynamic disorder they create can detrimentally affect the transport properties of van der Waals bonded molecular semiconductors. The low-energy nature of these vibrations makes it difficult to access them experimentally, which is why we still lack clear molecular design rules to control and reduce dynamic disorder. In this study we discuss the promising organic semiconductors rubrene, 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothio-phene and 2,9-di-decyl-dinaphtho-[2,3-b:20,30-f]-thieno-[3,2-b]-thiophene in terms of an exceptionally low degree of dynamic disorder. In particular, we analyse diffuse scattering in transmission electron microscopy, to show that small molecules that have their side chains attached along the long axis of their conjugated core are better encapsulated in their crystal structure, which helps reduce large-amplitude thermal motions. Our work provides a general strategy for the design of new classes of very high mobility organic semiconductors with a low degree of dynamic disorder. PMID:26898754

Quasielastic small-angle neutron scattering from heavy water solutions of cyclodextrins

NASA Astrophysics Data System (ADS)

Kusmin, André; Lechner, Ruep E.; Saenger, Wolfram

2011-01-01

We present a model for quasielastic neutron scattering (QENS) by an aqueous solution of compact and inflexible molecules. This model accounts for time-dependent spatial pair correlations between the atoms of the same as well as of distinct molecules and includes all coherent and incoherent neutron scattering contributions. The extension of the static theory of the excluded volume effect [A. K. Soper, J. Phys.: Condens. Matter 9, 2399 (1997)] to the time-dependent (dynamic) case allows us to obtain simplified model expressions for QENS spectra in the low Q region in the uniform fluid approximation. The resulting expressions describe the quasielastic small-angle neutron scattering (QESANS) spectra of D _2O solutions of native and methylated cyclodextrins well, yielding in particular translational and rotational diffusion coefficients of these compounds in aqueous solution. Finally, we discuss the full potential of the QESANS analysis (that is, beyond the uniform fluid approximation), in particular, the information on solute-solvent interactions (e.g., hydration shell properties) that such an analysis can provide, in principle.

A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis.

PubMed

Kerr, Georgina; Sheldon, Helen; Chaikuad, Apirat; Alfano, Ivan; von Delft, Frank; Bullock, Alex N; Harris, Adrian L

2015-04-01

Activin receptor-like kinase 1 (ALK1, encoded by the gene ACVRL1) is a type I BMP/TGF-β receptor that mediates signalling in endothelial cells via phosphorylation of SMAD1/5/8. During angiogenesis, sprouting endothelial cells specialise into tip cells and stalk cells. ALK1 synergises with Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2 and thereby represses tip cell formation and angiogenic sprouting. The ALK1-Fc soluble protein fusion has entered clinic trials as a therapeutic strategy to sequester the high-affinity extracellular ligand BMP9. Here, we determined the crystal structure of the ALK1 intracellular kinase domain and explored the effects of a small molecule kinase inhibitor K02288 on angiogenesis. K02288 inhibited BMP9-induced phosphorylation of SMAD1/5/8 in human umbilical vein endothelial cells to reduce both the SMAD and the Notch-dependent transcriptional responses. In endothelial sprouting assays, K02288 treatment induced a hypersprouting phenotype reminiscent of Notch inhibition. Furthermore, K02288 caused dysfunctional vessel formation in a chick chorioallantoic membrane assay of angiogenesis. Such activity may be advantageous for small molecule inhibitors currently in preclinical development for specific BMP gain of function conditions, including diffuse intrinsic pontine glioma and fibrodysplasia ossificans progressiva, as well as more generally for other applications in tumour biology.

Microgravity

NASA Image and Video Library

2001-01-24

Vapor Diffusion Apparatus (VDA and VDA-2) was developed by the University of Alabama in Birmingham for NASA's Marshall Space Flight Center. In the original VDA, a protein solution and a precipitant are extruded by two plungers onto the tip of a small syringe and allowed to evaporate, raising the concentration and prompting protein molecules to crystallize. In the VDA-2 version, a third plunger was added to mix the two solutions before returning the mix to the syringe tip. The principal investigator is Dr. Larry Delucas of the University of Alabama in Birmingham

Microgravity

NASA Image and Video Library

2001-01-24

Vapor Diffusion Apparatus (VDA-2) was developed by the University of Alabama in Birmingham for NASA's Marshall Space Flight Center. In the original VDA, a protein solution and a precipitant are extruded by two plungers onto the tip of a small syringe and allowed to evaporate, raising the concentration and prompting protein molecules to crystallize. In the VDA-2 version, a third plunger was added to mix the two solutions before returning the mix to the syringe tip. The principal investigator is Dr. Larry Delucas of the University of Alabama in Birmingham.

Diffuse X-ray scattering from benzil, C(14)H(10)O(2): analysis via automatic refinement of a Monte Carlo model.

PubMed

Welberry, T R; Goossens, D J; Edwards, A J; David, W I

2001-01-01

A recently developed method for fitting a Monte Carlo computer-simulation model to observed single-crystal diffuse X-ray scattering has been used to study the diffuse scattering in benzil, diphenylethanedione, C(6)H(5)-CO-CO-C(6)H(5). A model involving 13 parameters consisting of 11 intermolecular force constants, a single intramolecular torsional force constant and a local Debye-Waller factor was refined to give an agreement factor, R = [summation operator omega(Delta I)(2)/summation operator omega I(obs)(2)](1/2), of 14.5% for 101,324 data points. The model was purely thermal in nature. The analysis has shown that the diffuse lines, which feature so prominently in the observed diffraction patterns, are due to strong longitudinal displacement correlations. These are transmitted from molecule to molecule via a network of contacts involving hydrogen bonding of an O atom on one molecule and the para H atom of the phenyl ring of a neighbouring molecule. The analysis also allowed the determination of a torsional force constant for rotations about the single bonds in the molecule. This is the first diffuse scattering study in which measurement of such internal molecular torsion forces has been attempted.

Water Molecules and Hydrogen-Bonded Networks in Bacteriorhodopsin—Molecular Dynamics Simulations of the Ground State and the M-Intermediate

PubMed Central

Grudinin, Sergei; Büldt, Georg; Gordeliy, Valentin; Baumgaertner, Artur

2005-01-01

Protein crystallography provides the structure of a protein, averaged over all elementary cells during data collection time. Thus, it has only a limited access to diffusive processes. This article demonstrates how molecular dynamics simulations can elucidate structure-function relationships in bacteriorhodopsin (bR) involving water molecules. The spatial distribution of water molecules and their corresponding hydrogen-bonded networks inside bR in its ground state (G) and late M intermediate conformations were investigated by molecular dynamics simulations. The simulations reveal a much higher average number of internal water molecules per monomer (28 in the G and 36 in the M) than observed in crystal structures (18 and 22, respectively). We found nine water molecules trapped and 19 diffusive inside the G-monomer, and 13 trapped and 23 diffusive inside the M-monomer. The exchange of a set of diffusive internal water molecules follows an exponential decay with a 1/e time in the order of 340 ps for the G state and 460 ps for the M state. The average residence time of a diffusive water molecule inside the protein is ∼95 ps for the G state and 110 ps for the M state. We have used the Grotthuss model to describe the possible proton transport through the hydrogen-bonded networks inside the protein, which is built up in the picosecond-to-nanosecond time domains. Comparing the water distribution and hydrogen-bonded networks of the two different states, we suggest possible pathways for proton hopping and water movement inside bR. PMID:15731388

Chirality Differentiation by Diffusion in Chiral Nematic Liquid Crystals

NASA Astrophysics Data System (ADS)

Jiang, Jinghua; Yang, Deng-Ke

2017-01-01

Chirality is of great importance in the living world. It helps differentiate biochemical reactions such as those that take place during digestion. It may also help differentiate physical processes such as diffusion. Aiming to study the latter effect, we investigate the diffusion of guest chiral molecules in chiral nematic (cholesteric) liquid-crystal hosts. We discover that the diffusion dramatically depends on the handedness of the guest and host molecules and the chiral differentiation is greatly enhanced by the proper alignment of the liquid-crystal host. The diffusion of a guest chiral molecule in a chiral host with the same handedness is much faster than in a chiral host with opposite handedness. We also observe that the differentiation of chirality depends on the diffusion direction with respect to the twisting direction (helical axis). These results might be important in understanding effects of chirality on physical processes that take place in biological organisms. In addition, this effect could be utilized for enantiomer separation.

HF in clusters of molecular hydrogen. I. Size evolution of quantum solvation by parahydrogen molecules.

PubMed

Jiang, Hao; Bacić, Zlatko

2005-06-22

We present a theoretical study of the quantum solvation of the HF molecule by a small number of parahydrogen molecules, having n = 1-13 solvent particles. The minimum-energy cluster structures determined for n = 1-12 have all of the H(2) molecules in the first solvent shell. The first solvent shell closes at n = 12 and its geometry is icosahedral, with the HF molecule at the center. The quantum-mechanical ground-state properties of the clusters are calculated exactly using the diffusion Monte Carlo method. The zero-point energy of (p-H(2))(n)HF clusters is unusually large, amounting to 86% of the potential well depth for n > 7. The radial probability distribution functions (PDFs) confirm that the first solvent shell is complete for n = 12, and that the 13th p-H(2) molecule begins to fill the second solvent shell. The p-H(2) molecules execute large-amplitude motions and are highly mobile, making the solvent cage exceptionally fluxional. The anisotropy of the solvent, very pronounced for small clusters, decreases rapidly with increasing n, so that for n approximately 8-9 the solvent environment is practically isotropic. The analysis of the pair angular PDF reveals that for a given n, the parahydrogen solvent density around the HF is modulated in a pattern which clearly reflects the lowest-energy cluster configuration. The rigidity of the solvent clusters displays an interesting size dependence, increasing from n = 6 to 9, becoming floppier for n = 10, and increasing again up to n = 12, as the solvent shell is filled. The rigidity of the solvent cage appears to reach its maximum for n = 12, the point at which the first solvent shell is closed.

Observation of Spectral Diffusion in Crystals Using Single Impurity Molecules

DTIC Science & Technology

1990-10-31

from 12pentacene photophysical parameters including intersystem crossing . Apparently (and not surprisingly), the local pentacene environment this... pentacene molecules inp-terphenyl, both stable as well as spectrally diffusing single molecules can be observed. 20 DISTRIBUTION/AVAILABILITY OF ABSTRACT 121...with ultrathin sublimed crystals have removed this obstacle. For the case of pentacene impurities in crystals of p-terphenyl, we observe two radically

Chemical and Temperature Effects on Diffusion in a Model Polymer/Nanoparticle Composite

NASA Astrophysics Data System (ADS)

Janes, Dustin; Durning, Christopher

Polymers and inks used in medical devices may be strengthened with nanoparticle fillers, so an understanding of how they may affect the release of residuals and additives via diffusion will help modernize biocompatibility testing. Transport of small molecules in polymers with increasing volume fraction of impermeable nanoparticles is often poorly predicted by the simple Maxwell model for heterogeneous media. In this presentation we will examine two diffusant classes, only one of which possesses hydrogen bonding interactions with the nanoparticle surface. Since similar reductions in mutual diffusion coefficients were observed in both cases we attribute the enhancement of the ''blocking effect'' in nanocomposites to a reduction in polymer mobility in the interfacial volume near the nanoparticle. The temperature and penetrant concentration dependence of the diffusion coefficients were examined in the context of a Vrentas-Duda free volume model that includes a thermally activated prefactor. While data obtained for rubbery poly(methyl acrylate) clearly obeys the expected Arrhenius scaling with EA = 11 kJ/mol, results for films containing d = 14 nm spherical silica nanoparticles do not, providing more evidence that polymer free volume is perturbed in unexpected ways even for conceptually simple systems. National Science Foundation IGERT Program, Pall Corporation.

A Fiber Optic Interferometric Sensor Platform for Determining Gas Diffusivity in Zeolite Films.

PubMed

Yang, Ruidong; Xu, Zhi; Zeng, Shixuan; Jing, Wenheng; Trontz, Adam; Dong, Junhang

2018-04-04

Fiber optic interferometer (FOI) sensors have been fabricated by directly growing pure-silica MFI-type zeolite (i.e., silicalite) films on straight-cut endfaces of single-mode communication optical fibers. The FOI sensor has been demonstrated for determining molecular diffusivity in the zeolite by monitoring the temporal response of light interference from the zeolite film during the dynamic process of gas adsorption. The optical thickness of the zeolite film depends on the amount of gas adsorption that causes the light interference to shift upon loading molecules into the zeolitic channels. Thus, the time-dependence of the optical signal reflected from the coated zeolite film can represent the adsorption uptake curve, which allows computation of the diffusivity using models derived from the Fick’s Law equations. In this study, the diffusivity of isobutane in silicalite has been determined by the new FOI sensing method, and the results are in good agreement with literature values obtained by various conventional macroscopic techniques. The FOI sensor platform, because of its robustness and small size, could be useful for studying molecular diffusion in zeolitic materials under conditions that are inaccessible to the existing techniques.

Hydrogen in rocks: an energy source for deep microbial communities

NASA Technical Reports Server (NTRS)

Freund, Friedemann; Dickinson, J. Thomas; Cash, Michele

2002-01-01

To survive in deep subsurface environments, lithotrophic microbial communities require a sustainable energy source such as hydrogen. Though H2 can be produced when water reacts with fresh mineral surfaces and oxidizes ferrous iron, this reaction is unreliable since it depends upon the exposure of fresh rock surfaces via the episodic opening of cracks and fissures. A more reliable and potentially more voluminous H2 source exists in nominally anhydrous minerals of igneous and metamorphic rocks. Our experimental results indicate that H2 molecules can be derived from small amounts of H2O dissolved in minerals in the form of hydroxyl, OH- or O3Si-OH, whenever such minerals crystallized in an H2O-laden environment. Two types of experiments were conducted. Single crystal fracture experiments indicated that hydroxyl pairs undergo an in situ redox conversion to H2 molecules plus peroxy links, O3Si/OO\\SiO3. While the peroxy links become part of the mineral structure, the H2 molecules diffused out of the freshly fractured mineral surfaces. If such a mechanism occurred in natural settings, the entire rock column would become a volume source of H2. Crushing experiments to facilitate the outdiffusion of H2 were conducted with common crustal igneous rocks such as granite, andesite, and labradorite. At least 70 nmol of H2/g diffused out of coarsely crushed andesite, equivalent at standard pressure and temperature to 5,000 cm3 of H2/m3 of rock. In the water-saturated, biologically relevant upper portion of the rock column, the diffusion of H2 out of the minerals will be buffered by H2 saturation of the intergranular water film.

Structural basis for the selective permeability of channels made of communicating junction proteins.

PubMed

Ek-Vitorin, Jose F; Burt, Janis M

2013-01-01

The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore's limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions. Copyright © 2012 Elsevier B.V. All rights reserved.

A mathematical model of single target site location by Brownian movement in subcellular compartments.

PubMed

Kuthan, Hartmut

2003-03-07

The location of distinct sites is mandatory for many cellular processes. In the subcompartments of the cell nucleus, only very small numbers of diffusing macromolecules and specific target sites of some types may be present. In this case, we are faced with the Brownian movement of individual macromolecules and their "random search" for single/few specific target sites, rather than bulk-averaged diffusion and multiple sites. In this article, I consider the location of a distant central target site, e.g. a globular protein, by individual macromolecules executing unbiased (i.e. drift-free) random walks in a spherical compartment. For this walk-and-capture model, the closed-form analytic solution of the first passage time probability density function (p.d.f.) has been obtained as well as the first and second moment. In the limit of a large ratio of the radii of the spherical diffusion space and central target, well-known relations for the variance and the first two moments for the exponential p.d.f. were found to hold with high accuracy. These calculations reinforce earlier numerical results and Monte Carlo simulations. A major implication derivable from the model is that non-directed random movement is an effective means for locating single sites in submicron-sized compartments, even when the diffusion coefficients are comparatively small and the diffusing species are present in one copy only. These theoretical conclusions are underscored numerically for effective diffusion constants ranging from 0.5 to 10.0 microm(2) s(-1), which have been reported for a couple of nuclear proteins in their physiological environment. Spherical compartments of submicron size are, for example, the Cajal bodies (size: 0.1-1.0 microm), which are present in 1-5 copies in the cell nucleus. Within a small Cajal body of radius 0.1 microm a single diffusing protein molecule (with D=0.5 microm(2) s(-1)) would encounter a medium-sized protein of radius 2.5 nm within 1 s with a probability near certainty (p=0.98).

Histological evidence for drug diffusion across the cerebral meninges into the underlying neocortex in rats.

PubMed

Ludvig, Nandor; Sheffield, Lynette G; Tang, Hai M; Baptiste, Shirn L; Devinsky, Orrin; Kuzniecky, Ruben I

2008-01-10

Transmeningeal pharmacotherapy has been proposed to treat neurological disorders with localized pathology, such as intractable focal epilepsy. As a step toward understanding the diffusion and intracortical spread of transmeningeally delivered drugs, the present study used histological methods to determine the extent to which a marker compound, N-methyl-D-aspartate (NMDA), can diffuse into the neocortex through the meninges. Rats were implanted with bilateral parietal cortical epidural cups filled with 50 mM NMDA on the right side and artificial cerebrospinal fluid (ACSF) in the contralateral side. After 24 h, the histological effects of these treatments were evaluated using cresyl violet (Nissl) staining. The epidural NMDA exposure caused neuronal loss that in most animals extended from the pial surface through layer V. The area indicated by this neuronal loss was localized to the neocortical region underlying the epidural cup. These results suggest that NMDA-like, water soluble, small molecules can diffuse through the subdural/subarachnoid space into the underlying neocortex and spread in a limited fashion, close to the meningeal penetration site.

Molecular dynamics study of rhodamine 6G diffusion at n-decane-water interfaces.

PubMed

Popov, Piotr; Steinkerchner, Leo; Mann, Elizabeth K

2015-05-01

Two-dimensional diffusion of a rhodamine 6G fluorescent tracer molecule at the n-decane-water interface was studied with all-atom molecular dynamics simulations. In agreement with experimental data, we find increased mobility of the tracer at the n-decane-water interfaces in comparison to its mobility in bulk water. Orientational ordering of water and n-decane molecules near the interface is observed, and may change the interfacial viscosity as suggested to explain the experimental data. However, the restricted rotational motion of the rhodamine molecule at the interface suggests that the Saffman-Delbrück model may be a more appropriate approximation of rhodamine diffusion at n-decane-water interfaces, and, without any decrease in interfacial viscosity, suggests faster diffusion consistent with both experimental and simulation values.

Classification of Dynamical Diffusion States in Single Molecule Tracking Microscopy

PubMed Central

Bosch, Peter J.; Kanger, Johannes S.; Subramaniam, Vinod

2014-01-01

Single molecule tracking of membrane proteins by fluorescence microscopy is a promising method to investigate dynamic processes in live cells. Translating the trajectories of proteins to biological implications, such as protein interactions, requires the classification of protein motion within the trajectories. Spatial information of protein motion may reveal where the protein interacts with cellular structures, because binding of proteins to such structures often alters their diffusion speed. For dynamic diffusion systems, we provide an analytical framework to determine in which diffusion state a molecule is residing during the course of its trajectory. We compare different methods for the quantification of motion to utilize this framework for the classification of two diffusion states (two populations with different diffusion speed). We found that a gyration quantification method and a Bayesian statistics-based method are the most accurate in diffusion-state classification for realistic experimentally obtained datasets, of which the gyration method is much less computationally demanding. After classification of the diffusion, the lifetime of the states can be determined, and images of the diffusion states can be reconstructed at high resolution. Simulations validate these applications. We apply the classification and its applications to experimental data to demonstrate the potential of this approach to obtain further insights into the dynamics of cell membrane proteins. PMID:25099798

Permeability of uncharged organic molecules in reverse osmosis desalination membranes.

PubMed

Dražević, Emil; Košutić, Krešimir; Svalina, Marin; Catalano, Jacopo

2017-06-01

Reverse osmosis (RO) membranes are primarily designed for removal of salts i.e. for desalination of brackish and seawater, but they have also found applications in removal of organic molecules. While it is clear that steric exclusion is the dominant removal mechanism, the fundamental explanation for how and why the separation occurs remains elusive. Until recently there was no strong microscopic evidences elucidating the structure of the active polyamide layers of RO membranes, and thus they have been conceived as "black boxes"; or as an array of straight capillaries with a distribution of radii; or as polymers with a small amount of polymer free domains. The knowledge of diffusion and sorption coefficients is a prerequisite for understanding the intrinsic permeability of any organic solute in any polymer. At the same time, it is technically challenging to accurately measure these two fundamental parameters in very thin (20-300 nm) water-swollen active layers. In this work we have measured partition and diffusion coefficients and RO permeabilities of ten organic solutes in water-swollen active layers of two types of RO membranes, low (SWC4+) and high flux (XLE). We deduced from our results and recent microscopic studies that the solute flux of organic molecules in polyamide layer of RO membranes occurs in two domains, dense polymer (the key barrier layer) and the water filled domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion.

PubMed

Srikantha, Nishanthan; Mourad, Fatma; Suhling, Klaus; Elsaid, Naba; Levitt, James; Chung, Pei Hua; Somavarapu, Satyanarayana; Jackson, Timothy L

2012-09-01

The purpose of this study was to investigate the influence of molecular shape, conformability, net surface charge and tissue interaction on transscleral diffusion. Unfixed, porcine sclera was clamped in an Ussing chamber. Fluorophore-labelled neutral albumin, neutral dextran, or neutral ficoll were placed in one hemi-chamber and the rate of transscleral diffusion was measured over 24 h using a spectrophotometer. Experiments were repeated using dextrans and ficoll with positive or negative net surface charges. Fluorescence recovery after photobleaching (FRAP) was undertaken to compare transscleral diffusion with diffusion through a solution. All molecules were 70 kDa. With FRAP, the diffusion coefficient (D) of neutral molecules was highest for albumin, followed by ficoll, then dextran (p < 0.0001). Positive dextrans diffused fastest, followed by negative, then neutral dextrans (p = 0.0004). Neutral ficoll diffused the fastest, followed by positive then negative ficoll (p = 0.5865). For the neutral molecules, transscleral D was highest for albumin, followed by dextran, then ficoll (p < 0.0001). D was highest for negative ficoll, followed by neutral, then positive ficoll (p < 0.0001). By contrast, D was highest for positive dextran, followed by neutral, then negative dextran (p = 0.0021). In conclusion, diffusion in free solution does not predict transscleral diffusion and the molecular-tissue interaction is important. Molecular size, shape, and charge may all markedly influence transscleral diffusion, as may conformability to a lesser degree, but their effects may be diametrically opposed in different molecules, and their influence on diffusion is more complex than previously thought. Each variable cannot be considered in isolation, and the interplay of all these variables needs to be tested, when selecting or designing drugs for transscleral delivery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Surface transport mechanisms in molecular glasses probed by the exposure of nano-particles

NASA Astrophysics Data System (ADS)

Ruan, Shigang; Musumeci, Daniele; Zhang, Wei; Gujral, Ankit; Ediger, M. D.; Yu, Lian

2017-05-01

For a glass-forming liquid, the mechanism by which its surface contour evolves can change from bulk viscous flow at high temperatures to surface diffusion at low temperatures. We show that this mechanistic change can be conveniently detected by the exposure of nano-particles native in the material. Despite its high chemical purity, the often-studied molecular glass indomethacin contains low-concentration particles approximately 100 nm in size and 0.3% in volume fraction. Similar particles are present in polystyrene, another often-used model. In the surface-diffusion regime, particles are gradually exposed in regions vacated by host molecules, for example, the peak of a surface grating and the depletion zone near a surface crystal. In the viscous-flow regime, particle exposure is not observed. The surface contour around an exposed particle widens over time in a self-similar manner as 3 (Bt)1/4, where B is a surface mobility constant and the same constant obtained by surface grating decay. This work suggests that in a binary system composed of slow- and fast-diffusing molecules, slow-diffusing molecules can be stranded in surface regions vacated by fast-diffusing molecules, effectively leading to phase separation.

Complimentary aspects of diffusion imaging and fMRI: II. Elucidating contributions to the fMRI signal with diffusion sensitization.

PubMed

Mulkern, Robert V; Haker, Steven J; Maier, Stephan E

2007-07-01

Tissue water molecules reside in different biophysical compartments. For example, water molecules in the vasculature reside for variable periods of time within arteries, arterioles, capillaries, venuoles and veins, and may be within blood cells or blood plasma. Water molecules outside of the vasculature, in the extravascular space, reside, for a time, either within cells or within the interstitial space between cells. Within these different compartments, different types of microscopic motion that water molecules may experience have been identified and discussed. These range from Brownian diffusion to more coherent flow over the time scales relevant to functional magnetic resonance imaging (fMRI) experiments, on the order of several 10s of milliseconds. How these different types of motion are reflected in magnetic resonance imaging (MRI) methods developed for "diffusion" imaging studies has been an ongoing and active area of research. Here we briefly review the ideas that have developed regarding these motions within the context of modern "diffusion" imaging techniques and, in particular, how they have been accessed in attempts to further our understanding of the various contributions to the fMRI signal changes sought in studies of human brain activation.

Additional band broadening of peptides in the first size-exclusion chromatographic dimension of an automated stop-flow two-dimensional high performance liquid chromatography.

PubMed

Xu, Jucai; Sun-Waterhouse, Dongxiao; Qiu, Chaoying; Zhao, Mouming; Sun, Baoguo; Lin, Lianzhu; Su, Guowan

2017-10-27

The need to improve the peak capacity of liquid chromatography motivates the development of two-dimensional analysis systems. This paper presented a fully automated stop-flow two-dimensional liquid chromatography system with size exclusion chromatography followed by reversed phase liquid chromatography (SEC×RPLC) to efficiently separate peptides. The effects of different stop-flow operational parameters (stop-flow time, peak parking position, number of stop-flow periods and column temperature) on band broadening in the first dimension (1 st D) SEC column were quantitatively evaluated by using commercial small proteins and peptides. Results showed that the effects of peak parking position and the number of stop-flow periods on band broadening were relatively small. Unlike stop-flow analysis of large molecules with a long running time, additional band broadening was evidently observed for small molecule analytes due to the relatively high effective diffusion coefficient (D eff ). Therefore, shorter analysis time and lower 1 st D column temperature were suggested for analyzing small molecules. The stop-flow two-dimensional liquid chromatography (2D-LC) system was further tested on peanut peptides and an evidently improved resolution was observed for both stop-flow heart-cutting and comprehensive 2D-LC analysis (in spite of additional band broadening in SEC). The stop-flow SEC×RPLC, especially heart-cutting analysis with shorter analysis time and higher 1 st D resolution for selected fractions, offers a promising approach for efficient analysis of complex samples. Copyright © 2017 Elsevier B.V. All rights reserved.

A Diffusible Signal from Arbuscular Mycorrhizal Fungi Elicits a Transient Cytosolic Calcium Elevation in Host Plant Cells1[W

PubMed Central

Navazio, Lorella; Moscatiello, Roberto; Genre, Andrea; Novero, Mara; Baldan, Barbara; Bonfante, Paola; Mariani, Paola

2007-01-01

The implication of calcium as intracellular messenger in the arbuscular mycorrhizal (AM) symbiosis has not yet been directly demonstrated, although often envisaged. We used soybean (Glycine max) cell cultures stably expressing the bioluminescent Ca2+ indicator aequorin to detect intracellular Ca2+ changes in response to the culture medium of spores of Gigaspora margarita germinating in the absence of the plant partner. Rapid and transient elevations in cytosolic free Ca2+ were recorded, indicating that diffusible molecules released by the mycorrhizal fungus are perceived by host plant cells through a Ca2+-mediated signaling. Similar responses were also triggered by two Glomus isolates. The fungal molecules active in generating the Ca2+ transient were constitutively released in the medium, and the induced Ca2+ signature was not modified by the coculture of germinating spores with plant cells. Even ungerminated spores were able to generate the signaling molecules, as proven when the germination was blocked by a low temperature. The fungal molecules were found to be stable to heat treatment, of small molecular mass (<3 kD), and, on the basis of extraction with an organic solvent, partially lipophilic. Evidence for the specificity of such an early fungal signal to the AM symbiosis is suggested by the lack of a Ca2+ response in cultured cells of the nonhost plant Arabidopsis (Arabidopsis thaliana) and by the up-regulation in soybean cells of genes related to Medicago truncatula DMI1, DMI2, and DMI3 and considered essential for the establishment of the AM symbiosis. PMID:17142489

Diffusion of protein through the human cornea.

PubMed

Charalel, Resmi A; Engberg, Kristin; Noolandi, Jaan; Cochran, Jennifer R; Frank, Curtis; Ta, Christopher N

2012-01-01

To determine the rate of diffusion of myoglobin and bovine serum albumin (BSA) through the human cornea. These small proteins have hydrodynamic diameters of approximately 4.4 and 7.2 nm, and molecular weights of 16.7 and 66 kDa, for myoglobin and BSA, respectively. Diffusion coefficients were measured using a diffusion chamber where the protein of interest and balanced salt solution were in different chambers separated by an ex vivo human cornea. Protein concentrations in the balanced salt solution chamber were measured over time. Diffusion coefficients were calculated using equations derived from Fick's law and conservation of mass in a closed system. Our experiments demonstrate that the diffusion coefficient of myoglobin is 5.5 ± 0.9 × 10(-8) cm(2)/s (n = 8; SD = 1.3 × 10(-8) cm(2)/s; 95% CI: 4.6 × 10(-8) to 6.4 × 10(-8) cm(2)/s) and the diffusion coefficient of BSA is 3.1 ± 1.0 × 10(-8) cm(2)/s (n = 8; SD = 1.4 × 10(-8) cm(2)/s; 95% CI: 2.1 × 10(-8) to 4.1 × 10(-8) cm(2)/s). Our study suggests that molecules as large as 7.2 nm may be able to passively diffuse through the human cornea. With applications in pharmacotherapy and the development of an artificial cornea, further experiments are warranted to fully understand the limits of human corneal diffusion and its clinical relevance. Copyright © 2012 S. Karger AG, Basel.

Modeling solute clustering in the diffusion layer around a growing crystal.

PubMed

Shiau, Lie-Ding; Lu, Yung-Fang

2009-03-07

The mechanism of crystal growth from solution is often thought to consist of a mass transfer diffusion step followed by a surface reaction step. Solute molecules might form clusters in the diffusion step before incorporating into the crystal lattice. A model is proposed in this work to simulate the evolution of the cluster size distribution due to the simultaneous aggregation and breakage of solute molecules in the diffusion layer around a growing crystal in the stirred solution. The crystallization of KAl(SO(4))(2)12H(2)O from aqueous solution is studied to illustrate the effect of supersaturation and diffusion layer thickness on the number-average degree of clustering and the size distribution of solute clusters in the diffusion layer.

Application of Paramagnetically Tagged Molecules for Magnetic Resonance Imaging of Biofilm Mass Transport Processes▿

PubMed Central

Ramanan, B.; Holmes, W. M.; Sloan, W. T.; Phoenix, V. R.

2010-01-01

Molecules become readily visible by magnetic resonance imaging (MRI) when labeled with a paramagnetic tag. Consequently, MRI can be used to image their transport through porous media. In this study, we demonstrated that this method could be applied to image mass transport processes in biofilms. The transport of a complex of gadolinium and diethylenetriamine pentaacetic acid (Gd-DTPA), a commercially available paramagnetic molecule, was imaged both in agar (as a homogeneous test system) and in a phototrophic biofilm. The images collected were T1 weighted, where T1 is an MRI property of the biofilm and is dependent on Gd-DTPA concentration. A calibration protocol was applied to convert T1 parameter maps into concentration maps, thus revealing the spatially resolved concentrations of this tracer at different time intervals. Comparing the data obtained from the agar experiment with data from a one-dimensional diffusion model revealed that transport of Gd-DTPA in agar was purely via diffusion, with a diffusion coefficient of 7.2 × 10−10 m2 s−1. In contrast, comparison of data from the phototrophic biofilm experiment with data from a two-dimensional diffusion model revealed that transport of Gd-DTPA inside the biofilm was by both diffusion and advection, equivalent to a diffusion coefficient of 1.04 × 10−9 m2 s−1. This technology can be used to further explore mass transport processes in biofilms, either by using the wide range of commercially available paramagnetically tagged molecules and nanoparticles or by using bespoke tagged molecules. PMID:20435773

SPECIAL ISSUE DEVOTED TO THE 80TH BIRTHDAY OF S.A. AKHMANOV: Transient coherent anti-Stokes Raman scattering spectroscopy as a tool for measuring the diffusion coefficient and size of gas molecules

NASA Astrophysics Data System (ADS)

Nikitin, Sergei Yu

2009-07-01

Formulas are derived for evaluating the diffusion coefficient and size of gas molecules from transient coherent anti-Stokes Raman scattering measurements. Numerical estimates are presented for hydrogen.

Adenosine triphosphate diffusion through poly(ethylene glycol) diacrylate hydrogels can be tuned by cross-link density as measured by PFG-NMR

NASA Astrophysics Data System (ADS)

Majer, Günter; Southan, Alexander

2017-06-01

The diffusion of small molecules through hydrogels is of great importance for many applications. Especially in biological contexts, the diffusion of nutrients through hydrogel networks defines whether cells can survive inside the hydrogel or not. In this contribution, hydrogels based on poly(ethylene glycol) diacrylate with mesh sizes ranging from ξ = 1.1 to 12.9 nm are prepared using polymers with number-average molecular weights between Mn = 700 and 8000 g/mol. Precise measurements of diffusion coefficients D of adenosine triphosphate (ATP), an important energy carrier in biological systems, in these hydrogels are performed by pulsed field gradient nuclear magnetic resonance. Depending on the mesh size, ξ, and on the polymer volume fraction of the hydrogel after swelling, ϕ, it is possible to tune the relative ATP diffusion coefficient D/D0 in the hydrogels to values between 0.14 and 0.77 compared to the ATP diffusion coefficient D0 in water. The diffusion coefficients of ATP in these hydrogels are compared with predictions of various mathematical expressions developed under different model assumptions. The experimental data are found to be in good agreement with the predictions of a modified obstruction model or the free volume theory in combination with the sieving behavior of the polymer chains. No reasonable agreement was found with the pure hydrodynamic model.

Kinetics of the initial steps of G protein-coupled receptor-mediated cellular signaling revealed by single-molecule imaging.

PubMed

Lill, Yoriko; Martinez, Karen L; Lill, Markus A; Meyer, Bruno H; Vogel, Horst; Hecht, Bert

2005-08-12

We report on an in vivo single-molecule study of the signaling kinetics of G protein-coupled receptors (GPCR) performed using the neurokinin 1 receptor (NK1R) as a representative member. The NK1R signaling cascade is triggered by the specific binding of a fluorescently labeled agonist, substance P (SP). The diffusion of single receptor-ligand complexes in plasma membrane of living HEK 293 cells is imaged using fast single-molecule wide-field fluorescence microscopy at 100 ms time resolution. Diffusion trajectories are obtained which show intra- and intertrace heterogeneity in the diffusion mode. To investigate universal patterns in the diffusion trajectories we take the ligand-binding event as the common starting point. This synchronization allows us to observe changes in the character of the ligand-receptor-complex diffusion. Specifically, we find that the diffusion of ligand-receptor complexes is slowed down significantly and becomes more constrained as a function of time during the first 1000 ms. The decelerated and more constrained diffusion is attributed to an increasing interaction of the GPCR with cellular structures after the ligand-receptor complex is formed.

Fluorescence correlation spectroscopy diffusion laws to probe the submicron cell membrane organization.

PubMed

Wawrezinieck, Laure; Rigneault, Hervé; Marguet, Didier; Lenne, Pierre-François

2005-12-01

To probe the complexity of the cell membrane organization and dynamics, it is important to obtain simple physical observables from experiments on live cells. Here we show that fluorescence correlation spectroscopy (FCS) measurements at different spatial scales enable distinguishing between different submicron confinement models. By plotting the diffusion time versus the transverse area of the confocal volume, we introduce the so-called FCS diffusion law, which is the key concept throughout this article. First, we report experimental FCS diffusion laws for two membrane constituents, which are respectively a putative raft marker and a cytoskeleton-hindered transmembrane protein. We find that these two constituents exhibit very distinct behaviors. To understand these results, we propose different models, which account for the diffusion of molecules either in a membrane comprising isolated microdomains or in a meshwork. By simulating FCS experiments for these two types of organization, we obtain FCS diffusion laws in agreement with our experimental observations. We also demonstrate that simple observables derived from these FCS diffusion laws are strongly related to confinement parameters such as the partition of molecules in microdomains and the average confinement time of molecules in a microdomain or a single mesh of a meshwork.

The Diffuse Interstellar Bands: an Elderly Astro-Puzzle Rejuvenated

NASA Astrophysics Data System (ADS)

Cox, Nick L. J.

2011-12-01

The interstellar medium constitutes a physically and chemically complex component of galaxies and is important in the cycle of matter and the evolution of stars. From various spectroscopic clues we now know that the interstellar medium is rich in organic compounds. However, identifying the exact nature of all these components remains a challenge. In particular the identification of the so-called diffuse band carriers has been alluding astronomers for almost a century. In recent decades, observational, experimental and theoretical advances have rapidly lead to renewed interest in the diffuse interstellar bands (DIBs). This has been instigated partly by their perceived relation to the infrared aromatic emission bands, the UV extinction bump and far-UV rise, and the growing number of (small) organic molecules identified in space. This chapter gives an overview of the observational properties and behaviour of the DIBs, and their presence throughout the Universe. I will highlight recent progress in identifying their carriers and discuss their potential as tracers and probes of (extra)-Galactic ISM conditions.

The molecular chemistry of diffuse and translucent clouds in the line-of-sight to Sgr B2: Absorption by simple organic and inorganic molecules in the GBT PRIMOS survey

NASA Astrophysics Data System (ADS)

Corby, J. F.; McGuire, B. A.; Herbst, E.; Remijan, A. J.

2018-02-01

The 1-50 GHz PRebiotic Interstellar MOlecular Survey (PRIMOS) contains 50 molecular absorption lines observed in clouds located in the line-of-sight to Sgr B2(N). The line-of-sight material is associated with diffuse and translucent clouds located in the Galactic center, bar, and spiral arms in the disk. We measured the column densities and estimate abundances, relative to H2, of 11 molecules and additional isotopologues observed in this material. We used absorption by optically thin transitions of c-C3H2 to estimate the molecular hydrogen columns, and argue that this method is preferable to more commonly used methods. We discuss the kinematic structure and abundance patterns of small molecules including the sulfur-bearing species CS, SO, CCS, H2CS, and HCS+; oxygen-bearing molecules OH, SiO, and H2CO; and simple hydrocarbon molecules c-C3H2, l-C3H, and l-C3H+. Finally, we discuss the implications of the observed chemistry for the structure of the gas and dust in the ISM. Highlighted results include the following. First, whereas gas in the disk has a molecular hydrogen fraction of 0.65, clouds on the outer edge of the Galactic bar and in or near the Galactic center have molecular fractions of 0.85 and >0.9, respectively. Second, we observe trends in isotope ratios with Galactocentric distance; while carbon and silicon show enhancement of the rare isotopes at low Galactocentric distances, sulfur exhibits no trend with Galactocentric distance. We also determine that the ratio of c-C3H2/c-H13CCCH provides a good estimate of the 12C/13C ratio, whereas H2CO/H213CO exhibits fractionation. Third, we report the presence of l-C3H+ in diffuse clouds for the first time. Finally, we suggest that CS has an enhanced abundance within higher density clumps of material in the disk, and therefore may be diagnostic of cloud conditions. If this holds, the diffuse clouds in the Galactic disk contain multiple embedded hyperdensities in a clumpy structure, and the density profile is not a simple function of AV. The reduced spectra (FITS files) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A10

Biomimetic air sampling for detection of low concentrations of molecules and bioagents : LDRD 52744 final report.

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

Hughes, Robert Clark

2003-12-01

Present methods of air sampling for low concentrations of chemicals like explosives and bioagents involve noisy and power hungry collectors with mechanical parts for moving large volumes of air. However there are biological systems that are capable of detecting very low concentrations of molecules with no mechanical moving parts. An example is the silkworm moth antenna which is a highly branched structure where each of 100 branches contains about 200 sensory 'hairs' which have dimensions of 2 microns wide by 100 microns long. The hairs contain about 3000 pores which is where the gas phase molecules enter the aqueous (lymph)more » phase for detection. Simulations of diffusion of molecules indicate that this 'forest' of hairs is 'designed' to maximize the extraction of the vapor phase molecules. Since typical molecules lose about 4 decades in diffusion constant upon entering the liquid phase, it is important to allow air diffusion to bring the molecule as close to the 'sensor' as possible. The moth acts on concentrations as low as 1000 molecules per cubic cm. (one part in 1e16). A 3-D collection system of these dimensions could be fabricated by micromachining techniques available at Sandia. This LDRD addresses the issues involved with extracting molecules from air onto micromachined structures and then delivering those molecules to microsensors for detection.« less

Macromolecular Crowding Studies of Amino Acids Using NMR Diffusion Measurements and Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Virk, Amninder; Stait-Gardner, Timothy; Willis, Scott; Torres, Allan; Price, William

2015-02-01

Molecular crowding occurs when the total concentration of macromolecular species in a solution is so high that a considerable proportion of the volume is physically occupied and therefore not accessible to other molecules. This results in significant changes in the solution properties of the molecules in such systems. Macromolecular crowding is ubiquitous in biological systems due to the generally high intracellular protein concentrations. The major hindrance to understanding crowding is the lack of direct comparison of experimental data with theoretical or simulated data. Self-diffusion is sensitive to changes in the molecular weight and shape of the diffusing species, and the available diffusion space (i.e., diffusive obstruction). Consequently, diffusion measurements are a direct means for probing crowded systems including the self-association of molecules. In this work, nuclear magnetic resonance measurements of the self-diffusion of four amino acids (glycine, alanine, valine and phenylalanine) up to their solubility limit in water were compared directly with molecular dynamics simulations. The experimental data were then analyzed using various models of aggregation and obstruction. Both experimental and simulated data revealed that the diffusion of both water and the amino acids were sensitive to the amino acid concentration. The direct comparison of the simulated and experimental data afforded greater insights into the aggregation and obstruction properties of each amino acid.

Improving receiver performance of diffusive molecular communication with enzymes.

PubMed

Noel, Adam; Cheung, Karen C; Schober, Robert

2014-03-01

This paper studies the mitigation of intersymbol interference in a diffusive molecular communication system using enzymes that freely diffuse in the propagation environment. The enzymes form reaction intermediates with information molecules and then degrade them so that they cannot interfere with future transmissions. A lower bound expression on the expected number of molecules measured at the receiver is derived. A simple binary receiver detection scheme is proposed where the number of observed molecules is sampled at the time when the maximum number of molecules is expected. Insight is also provided into the selection of an appropriate bit interval. The expected bit error probability is derived as a function of the current and all previously transmitted bits. Simulation results show the accuracy of the bit error probability expression and the improvement in communication performance by having active enzymes present.

Dynamic behaviors and transport properties of ethanol molecules in transmembrane cyclic peptide nanotubes.

PubMed

Li, Rui; Fan, Jianfen; Li, Hui; Yan, Xiliang; Yu, Yi

2015-07-07

Classical molecular dynamics simulations have been performed to investigate the dynamic behaviors and transport properties of ethanol molecules in transmembrane cyclic peptide nanotubes (CPNTs) with various radii, i.e., 8×(WL¯)n=3,4,5/POPE. The results show that ethanol molecules spontaneously fill the octa- and deca-CPNTs, but not the hexa-CPNT. In the octa-CPNT, ethanol molecules are trapped at individual gaps with their carbon skeletons perpendicular to the tube axis and hydroxyl groups towards the tube wall, forming a broken single-file chain. As the channel radius increases, ethanol molecules inside the deca-CPNT tend to form a tubular layer and the hydroxyl groups mainly stretch towards the tube axis. Computations of diffusion coefficients indicate that ethanol molecules in the octa-CPNT nearly lost their diffusion abilities, while those in the deca-CPNT diffuse as 4.5 times as in a (8, 8) carbon nanotube with a similar tube diameter. The osmotic and diffusion permeabilities (pf and pd, respectively) of the octa- and deca-CPNTs transporting ethanol were deduced for the first time. The distributions of the gauche and trans conformers of ethanol molecules in two CPNTs are quite similar, both with approximately 57% gauche conformers. The non-bonded interactions of channel ethanol with a CPNT wall and surrounding ethanol were explored. The potential of mean force elucidates the mechanism underlying the transporting characteristics of channel ethanol in a transmembrane CPNT.

Physical re-examination of parameters on a molecular collisions-based diffusion model for diffusivity prediction in polymers.

PubMed

Ohashi, Hidenori; Tamaki, Takanori; Yamaguchi, Takeo

2011-12-29

Molecular collisions, which are the microscopic origin of molecular diffusive motion, are affected by both the molecular surface area and the distance between molecules. Their product can be regarded as the free space around a penetrant molecule defined as the "shell-like free volume" and can be taken as a characteristic of molecular collisions. On the basis of this notion, a new diffusion theory has been developed. The model can predict molecular diffusivity in polymeric systems using only well-defined single-component parameters of molecular volume, molecular surface area, free volume, and pre-exponential factors. By consideration of the physical description of the model, the actual body moved and which neighbor molecules are collided with are the volume and the surface area of the penetrant molecular core. In the present study, a semiempirical quantum chemical calculation was used to calculate both of these parameters. The model and the newly developed parameters offer fairly good predictive ability. © 2011 American Chemical Society

An adsorption diffusion model for removal of para-chlorophenol by activated carbon derived from bituminous coal.

PubMed

Sze, M F F; McKay, G

2010-05-01

Batch adsorption experiments were carried out to study the adsorptive removal and diffusion mechanism of para-chlorophenol (p-CP) onto Calgon Filtrasorb 400 (F400) activated carbon. The external mass transfer resistance is negligible in the adsorption process carried out under different conditions in batch operation. Intraparticle diffusion model plots were used to correlate the batch p-CP adsorption data; three distinct linear sections were obtained for every batch operation. The textural properties of F400 activated carbon showed that it has a large portion of supermicropores, which is comparable to the size of the p-CP molecules. Due to the stronger interactions between p-CP molecules and F400 micropores, p-CP molecules predominantly diffused and occupied active sites in micropore region by hopping mechanism, and eventually followed by a slow filling of mesopores and micropores. This hypothesis is proven by the excellent agreement of the intraparticle diffusion model plots and the textural properties of F400 activated carbon. Copyright 2009 Elsevier Ltd. All rights reserved.

PCNA appears in two populations of slow and fast diffusion with a constant ratio throughout S-phase in replicating mammalian cells.

PubMed

Zessin, Patrick J M; Sporbert, Anje; Heilemann, Mike

2016-01-13

DNA replication is a fundamental cellular process that precedes cell division. Proliferating cell nuclear antigen (PCNA) is a central scaffold protein that orchestrates DNA replication by recruiting many factors essential for the replication machinery. We studied the mobility of PCNA in live mammalian cells using single-particle tracking in combination with photoactivated-localization microscopy (sptPALM) and found two populations. The first population which is only present in cells with active DNA replication, showed slow diffusion and was found to be located in replication foci. The second population showed fast diffusion, and represents the nucleoplasmic pool of unbound PCNA not involved in DNA replication. The ratio of these two populations remained constant throughout different stages of S-phase. A fraction of molecules in both populations showed spatially constrained mobility. We determined an exploration radius of ~100 nm for 13% of the slow-diffusing PCNA molecules, and of ~600 nm for 46% of the fast-diffusing PCNA molecules.

Properties of grains derived from IRAS observations of dust

NASA Technical Reports Server (NTRS)

Wesselius, P. R.; Chlewicki, Grzegorz; Laureijs, Rene J.

1989-01-01

The authors used the results of Infrared Astronomy Satellite (IRAS) observations of diffuse medium dust to develop a theoretical model of the infrared properties of grains. Recent models based entirely on traditional observations of extinction and polarization include only particles whose equilibrium temperatures do not exceed 20 K in the diffuse interstellar medium. These classical grains, for which the authors have adopted the multipopulation model developed by Hong and Greenberg (1980), can explain only the emission in the IRAS 100 micron band. The measurements at shorter wavelengths (12, 25 and 60 microns) require two new particle populations. Vibrational fluorescence from aromatic molecules provides the most likely explanation for the emission observed at 12 microns, with polycyclic aeromatic hydrocarbons (PAHs) containing about 10 percent of cosmic carbon. A simplified model of the emission process shows that PAH molecules can also explain most of the emission measured by IRAS at 25 microns. The authors identified the warm particles responsible for the excess 60 microns emission with small (a approx. equals 0.01 microns) iron grains. A compilation of the available data on the optical properties of iron indicates that the diffuse medium temperature of small iron particles should be close to 50 K and implies that a large, possibly dominant, fraction of cosmic iron must be locked up in metallic particles in order to match the observed 60 microns intensities. The model matches the infrared fluxes typically observed by IRAS in the diffuse medium and can also reproduce the infrared surface brightness distribution in individual clouds. In particular, the combination of iron and classical cool grains can explain the surprising observations of the 60/100 microns flux ratio in clouds, which is either constant or increases slightly towards higher opacities. The presence of metallic grains has significant implications for the physics of the interstellar medium, including catalytic H2 formation, for which iron grains could be the main site; differences in depletion patterns between iron and other refractory elements (Mg, Si); and superparamagnetic behavior of large grains with embedded iron clusters giving rise to the observed high degree of alignment by the galactic magnetic field.

Diffusion modulation of DNA by toehold exchange

NASA Astrophysics Data System (ADS)

Rodjanapanyakul, Thanapop; Takabatake, Fumi; Abe, Keita; Kawamata, Ibuki; Nomura, Shinichiro M.; Murata, Satoshi

2018-05-01

We propose a method to control the diffusion speed of DNA molecules with a target sequence in a polymer solution. The interaction between solute DNA and diffusion-suppressing DNA that has been anchored to a polymer matrix is modulated by the concentration of the third DNA molecule called the competitor by a mechanism called toehold exchange. Experimental results show that the sequence-specific modulation of the diffusion coefficient is successfully achieved. The diffusion coefficient can be modulated up to sixfold by changing the concentration of the competitor. The specificity of the modulation is also verified under the coexistence of a set of DNA with noninteracting base sequences. With this mechanism, we are able to control the diffusion coefficient of individual DNA species by the concentration of another DNA species. This methodology introduces a programmability to a DNA-based reaction-diffusion system.

Visualizing single molecules interacting with nuclear pore complexes by narrow-field epifluorescence microscopy

PubMed Central

Yang, Weidong; Musser, Siegfried M.

2008-01-01

The utility of single molecule fluorescence (SMF) for understanding biological reactions has been amply demonstrated by a diverse series of studies over the last decade. In large part, the molecules of interest have been limited to those within a small focal volume or near a surface to achieve the high sensitivity required for detecting the inherently weak signals arising from individual molecules. Consequently, the investigation of molecular behavior with high time and spatial resolution deep within cells using SMF has remained challenging. Recently, we demonstrated that narrow-field epifluorescence microscopy allows visualization of nucleocytoplasmic transport at the single cargo level. We describe here the methodological approach that yields 2 ms and ∼15 nm resolution for a stationary particle. The spatial resolution for a mobile particle is inherently worse, and depends on how fast the particle is moving. The signal-to-noise ratio is sufficiently high to directly measure the time a single cargo molecule spends interacting with the nuclear pore complex. Particle tracking analysis revealed that cargo molecules randomly diffuse within the nuclear pore complex, exiting as a result of a single rate-limiting step. We expect that narrow-field epifluorescence microscopy will be useful for elucidating other binding and trafficking events within cells. PMID:16879979

Lateral diffusion in model membranes is independent of the size of the hydrophobic region of molecules.

PubMed Central

Balcom, B J; Petersen, N O

1993-01-01

We have systematically investigated the probe size and shape dependence of lateral diffusion in model dimyristoyl phosphatidylcholine membranes. Linear hydrophobic polymers, which differ in length by an order of magnitude, were used to explore the effect on the lateral diffusion coefficient of hydrodynamic restrictions in the bilayer interior. The polymers employed are isoprenoid alcohols--citronellol, solanesol, and dolichol. Tracer lateral diffusion coefficients were measured by fluorescence photobleaching recovery. Despite the large difference in lengths, the nitrobenzoxadiazole labelled alcohols all diffuse at the rate of lipid self-diffusion (5.0 x 10(-12) m2 s-1, 29 degrees C) in the liquid crystal phase. Companion measurements in isotropic polymer solution, in gel phase lipid membranes and with nonpolar fluorescent polyaromatic hydrocarbons, show a marked dependence of the lateral diffusion coefficient on the probe molecule size. Our results in the liquid crystal phase are in accord with free area theory which asserts that lateral diffusion in the membrane is restricted by the surface-free area. Probe molecules which are significantly longer than the host phospholipid, seven times longer in the case of dolichol, are still restricted in their lateral motion by the surface properties of the bilayer in the liquid crystal phase. Fluorescence quenching experiments indicate that the nitrobenzoxadiazole label does not reside at the aqueous interface, although it must reside in close proximity according to the diffusion measurements. PMID:8218892

Evaluation of Proteins' Rotational Diffusion Coefficients from Simulations of Their Free Brownian Motion in Volume-Occupied Environments.

PubMed

Długosz, Maciej; Antosiewicz, Jan M

2014-01-14

We have investigated the rotational dynamics of hen egg white lysozyme in monodisperse aqueous solutions of concentrations up to 250 mg/mL, using a rigid-body Brownian dynamics method that accurately accounts for anisotropies of diffusing objects. We have examined the validity of the free diffusion concept in the analysis of computer simulations of volume-occupied molecular solutions. We have found that, when as the only intermolecular interaction, the excluded volume effect is considered, rotational diffusion of molecules adheres to the free diffusion model. Further, we present a method based on the exact (in the case of the free diffusion) analytic forms of autocorrelation functions of particular vectors rigidly attached to diffusing objects, which allows one to obtain from results of molecular simulations the three principal rotational diffusion coefficients characterizing rotational Brownian motion of an arbitrarily shaped rigid particle for an arbitrary concentration of crowders. We have applied this approach to trajectories resulting from Brownian dynamics simulations of hen egg white lysozyme solutions. We show that the apparent anisotropy of proteins' rotational motions increases with an increasing degree of crowding. Finally, we demonstrate that even if the hydrodynamic anisotropy of molecules is neglected and molecules are simulated using their average translational and rotational diffusion coefficients, excluded volume effects still lead to their anisotropic rotational dynamics.

Nanopipette Delivery of Individual Molecules to Cellular Compartments for Single-Molecule Fluorescence Tracking

PubMed Central

Bruckbauer, Andreas; James, Peter; Zhou, Dejian; Yoon, Ji Won; Excell, David; Korchev, Yuri; Jones, Roy; Klenerman, David

2007-01-01

We have developed a new method, using a nanopipette, for controlled voltage-driven delivery of individual fluorescently labeled probe molecules to the plasma membrane which we used for single-molecule fluorescence tracking (SMT). The advantages of the method are 1), application of the probe to predefined regions on the membrane; 2), release of only one or a few molecules onto the cell surface; 3), when combined with total internal reflection fluorescence microscopy, very low background due to unbound molecules; and 4), the ability to first optimize the experiment and then repeat it on the same cell. We validated the method by performing an SMT study of the diffusion of individual membrane glycoproteins labeled with Atto 647-wheat germ agglutin in different surface domains of boar spermatozoa. We found little deviation from Brownian diffusion with a mean diffusion coefficient of 0.79 ± 0.04 μm2/s in the acrosomal region and 0.10 ± 0.02 μm2/s in the postacrosomal region; this difference probably reflects different membrane structures. We also showed that we can analyze diffusional properties of different subregions of the cell membrane and probe for the presence of diffusion barriers. It should be straightforward to extend this new method to other probes and cells, and it can be used as a new tool to investigate the cell membrane. PMID:17631532

Molecular Dynamics Simulations of the Oil-Detachment from the Hydroxylated Silica Surface: Effects of Surfactants, Electrostatic Interactions, and Water Flows on the Water Molecular Channel Formation.

PubMed

Tang, Jian; Qu, Zhou; Luo, Jianhui; He, Lanyan; Wang, Pingmei; Zhang, Ping; Tang, Xianqiong; Pei, Yong; Ding, Bin; Peng, Baoliang; Huang, Yunqing

2018-02-15

The detachment process of an oil molecular layer situated above a horizontal substrate was often described by a three-stage process. In this mechanism, the penetration and diffusion of water molecules between the oil phase and the substrate was proposed to be a crucial step to aid in removal of oil layer/drops from substrate. In this work, the detachment process of a two-dimensional alkane molecule layer from a silica surface in aqueous surfactant solutions is studied by means of molecular dynamics (MD) simulations. By tuning the polarity of model silica surfaces, as well as considering the different types of surfactant molecules and the water flow effects, more details about the formation of water molecular channel and the expansion processes are elucidated. It is found that for both ionic and nonionic type surfactant solutions, the perturbation of surfactant molecules on the two-dimensional oil molecule layer facilitates the injection and diffusion of water molecules between the oil layer and silica substrate. However, the water channel formation and expansion speed is strongly affected by the substrate polarity and properties of surfactant molecules. First, only for the silica surface with relative stronger polarity, the formation of water molecular channel is observed. Second, the expansion speed of the water molecular channel upon the ionic surfactant (dodecyl trimethylammonium bromide, DTAB and sodium dodecyl benzenesulfonate, SDBS) flooding is more rapidly than the nonionic surfactant system (octylphenol polyoxyethylene(10) ether, OP-10). Third, the water flow speed may also affect the injection and diffusion of water molecules. These simulation results indicate that the water molecular channel formation process is affected by multiple factors. The synergistic effects of perturbation of surfactant molecules and the electrostatic interactions between silica substrate and water molecules are two key factors aiding in the injection and diffusion of water molecules and helpful for the oil detachment from silica substrate.

The origin of life is a spatially localized stochastic transition

PubMed Central

2012-01-01

Background Life depends on biopolymer sequences as catalysts and as genetic material. A key step in the Origin of Life is the emergence of an autocatalytic system of biopolymers. Here we study computational models that address the way a living autocatalytic system could have emerged from a non-living chemical system, as envisaged in the RNA World hypothesis. Results We consider (i) a chemical reaction system describing RNA polymerization, and (ii) a simple model of catalytic replicators that we call the Two’s Company model. Both systems have two stable states: a non-living state, characterized by a slow spontaneous rate of RNA synthesis, and a living state, characterized by rapid autocatalytic RNA synthesis. The origin of life is a transition between these two stable states. The transition is driven by stochastic concentration fluctuations involving relatively small numbers of molecules in a localized region of space. These models are simulated on a two-dimensional lattice in which reactions occur locally on single sites and diffusion occurs by hopping of molecules to neighbouring sites. Conclusions If diffusion is very rapid, the system is well-mixed. The transition to life becomes increasingly difficult as the lattice size is increased because the concentration fluctuations that drive the transition become relatively smaller when larger numbers of molecules are involved. In contrast, when diffusion occurs at a finite rate, concentration fluctuations are local. The transition to life occurs in one local region and then spreads across the rest of the surface. The transition becomes easier with larger lattice sizes because there are more independent regions in which it could occur. The key observations that apply to our models and to the real world are that the origin of life is a rare stochastic event that is localized in one region of space due to the limited rate of diffusion of the molecules involved and that the subsequent spread across the surface is deterministic. It is likely that the time required for the deterministic spread is much shorter than the waiting time for the origin, in which case life evolves only once on a planet, and then rapidly occupies the whole surface. Reviewers Reviewed by Omer Markovitch (nominated by Doron Lancet), Claus Wilke, and Nobuto Takeuchi (nominated by Eugene Koonin). PMID:23176307

Anomalous Extracellular Diffusion in Rat Cerebellum

PubMed Central

Xiao, Fanrong; Hrabe, Jan; Hrabetova, Sabina

2015-01-01

Extracellular space (ECS) is a major channel transporting biologically active molecules and drugs in the brain. Diffusion-mediated transport of these substances is hindered by the ECS structure but the microscopic basis of this hindrance is not fully understood. One hypothesis proposes that the hindrance originates in large part from the presence of dead-space (DS) microdomains that can transiently retain diffusing molecules. Because previous theoretical and modeling work reported an initial period of anomalous diffusion in similar environments, we expected that brain regions densely populated by DS microdomains would exhibit anomalous extracellular diffusion. Specifically, we targeted granular layers (GL) of rat and turtle cerebella that are populated with large and geometrically complex glomeruli. The integrative optical imaging (IOI) method was employed to evaluate diffusion of fluorophore-labeled dextran (MW 3000) in GL, and the IOI data analysis was adapted to quantify the anomalous diffusion exponent dw from the IOI records. Diffusion was significantly anomalous in rat GL, where dw reached 4.8. In the geometrically simpler turtle GL, dw was elevated but not robustly anomalous (dw = 2.6). The experimental work was complemented by numerical Monte Carlo simulations of anomalous ECS diffusion in several three-dimensional tissue models containing glomeruli-like structures. It demonstrated that both the duration of transiently anomalous diffusion and the anomalous exponent depend on the size of model glomeruli and the degree of their wrapping. In conclusion, we have found anomalous extracellular diffusion in the GL of rat cerebellum. This finding lends support to the DS microdomain hypothesis. Transiently anomalous diffusion also has a profound effect on the spatiotemporal distribution of molecules released into the ECS, especially at diffusion distances on the order of a few cell diameters, speeding up short-range diffusion-mediated signals in less permeable structures. PMID:25954895

Diffusivity Measurements of Volatile Organics in Levitated Viscous Aerosol Particles

NASA Astrophysics Data System (ADS)

Bastelberger, Sandra; Krieger, Ulrich; Luo, Beiping; Peter, Thomas

2017-04-01

Field measurements indicating that atmospheric secondary aerosol (SOA) particles can be present in a highly viscous, glassy state have spurred numerous studies addressing low water diffusivities in glassy aerosols, focusing on kinetic limitations to hygroscopic growth and the plasticizing effect of water. Less is known about diffusion limitations of organic molecules and oxidants in viscous matrices and how these might affect atmospheric chemistry and gas-particle phase partitioning of complex mixtures with constituents of different volatility. Often viscosity data has been used to infer diffusivity via the Stokes- Einstein relationship even though strong deviations from this relationship have been observed for matrices of high viscosity. In this study, we provide a quantitative estimate for the diffusivity of a volatile organic in a viscous matrix. Evaporation of single particles generated from an aqueous solution of sucrose and a small quantity of volatile tetraethylene glycol (PEG-4) is investigated in an electrodynamic balance at controlled relative humidity (RH) and temperature conditions, thereby varying the viscosity of the sucrose matrix. The evaporative loss of tetraethylene glycol as determined by Mie resonance spectroscopy is used in conjunction with a diffusion model to retrieve translational diffusion coefficients of tetraethylene glycol. The evaporation of PEG-4 shows a pronounced RH and temperature dependence and is severely depressed for RH 30% corresponding to diffusivities < 10-14 cm2/s at temperatures as high as 15 °C, implying that atmospheric volatile organic compounds (VOC) can be subject to severe diffusion limitations in glassy SOA. Comparison of the experimentally derived diffusivities with viscosity estimates for the ternary system reveals a breakdown of the Stokes-Einstein relationship.

Probing the Interplay between Dendritic Spine Morphology and Membrane-Bound Diffusion.

PubMed

Adrian, Max; Kusters, Remy; Storm, Cornelis; Hoogenraad, Casper C; Kapitein, Lukas C

2017-11-21

Dendritic spines are protrusions along neuronal dendrites that harbor the majority of excitatory postsynapses. Their distinct morphology, often featuring a bulbous head and small neck that connects to the dendritic shaft, has been shown to facilitate compartmentalization of electrical and cytoplasmic signaling stimuli elicited at the synapse. The extent to which spine morphology also forms a barrier for membrane-bound diffusion has remained unclear. Recent simulations suggested that especially the diameter of the spine neck plays a limiting role in this process. Here, we examine the connection between spine morphology and membrane-bound diffusion through a combination of photoconversion, live-cell superresolution experiments, and numerical simulations. Local photoconversion was used to obtain the timescale of diffusive equilibration in spines and followed by global sparse photoconversion to determine spine morphologies with nanoscopic resolution. These morphologies were subsequently used to assess the role of morphology on the diffusive equilibration. From the simulations, we could determine a robust relation between the equilibration timescale and a generalized shape factor calculated using both spine neck width and neck length, as well as spine head size. Experimentally, we found that diffusive equilibration was often slower, but rarely faster than predicted from the simulations, indicating that other biological confounders further reduce membrane-bound diffusion in these spines. This shape-dependent membrane-bound diffusion in mature spines may contribute to spine-specific compartmentalization of neurotransmitter receptors and signaling molecules and thereby support long-term plasticity of synaptic contacts. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Model colloid system for interfacial sorption kinetics

NASA Astrophysics Data System (ADS)

Salipante, Paul; Hudson, Steven

2014-11-01

Adsorption kinetics of nanometer scale molecules, such as proteins at interfaces, is usually determined through measurements of surface coverage. Their small size limits the ability to directly observe individual molecule behavior. To better understand the behavior of nanometer size molecules and the effect on interfacial kinetics, we use micron size colloids with a weak interfacial interaction potential as a model system. Thus, the interaction strength is comparable to many nanoscale systems (less than 10 kBT). The colloid-interface interaction potential is tuned using a combination of depletion, electrostatic, and gravitational forces. The colloids transition between an entropically trapped adsorbed state and a desorbed state through Brownian motion. Observations are made using an LED-based Total Internal Reflection Microscopy (TIRM) setup. The observed adsorption and desorption rates are compared theoretical predictions based on the measured interaction potential and near wall particle diffusivity. This experimental system also allows for the study of more complex dynamics such as nonspherical colloids and collective effects at higher concentrations.

Preventing Small Molecule Nucleation and Crystallization by Sequestering in a Micelle Corona

NASA Astrophysics Data System (ADS)

Li, Ziang; Johnson, Lindsay; Ricarte, Ralm; Yao, Letitia; Hillmyer, Marc; Bates, Frank; Lodge, Timothy

We exploited a blend of hydroxypropyl methylcellulose acetate succinate and poly(N-isopropylacrylamide) (PNIPAm) to improve the solubility and dissolution of a rapidly crystallizing model drug molecule phenytoin and observed synergistic effect in vitro at constant drug loading by varying the blending ratio. Dynamic and static light scattering experiments showed that PNIPAm self-assembled into micelles in aqueous solution. We believe that adding these PNIPAm micelles inhibited both nucleation and crystal growth of phenytoin based on the polarized light micrographs taken from the dissolution media. The drug-polymer intermolecular interaction was revealed by nuclear Overhauser effect spectroscopy and further quantified by diffusion ordered spectroscopy. We found that the phenytoin molecules were sequestered in aqueous solution by partitioning into the corona of the micelle. The blend strategy through the use of self-assembled micelles showcased in this study offers a new platform for designing advanced excipients for oral drug delivery. This study was funded by The Dow Chemical Company through Agreement 224249AT with the University of Minnesota.

Application of pulsed-gradient Fourier transform nuclear magnetic resonance to the study of self-diffusion of phospholipid vesicles.

PubMed

McDonald, G G; Vanderkooi, J M

1975-05-20

A pulsed-gradient Fourier transform nuclear magnetic resonance (NMR) technique was appplied to the study of diffusion of phospholipid vesicles. The diffusion coefficient of dimyristoyllecithin vesicles (DML) in a D2O-phospahte buffer at 37 degrees is D = 1.9 TIMES 10(-6) cm2/sec. In a solution made viscous by DNA addition, the diffusion coefficient of DML vesicles was 3.5 times 10(-7) cm2/sec. These values compare favorably with the diffusion rate for liposomes as determined by ultracentrifugation and by Stokes law calculation. The data suggest that DML diffusion is controlled primarily by whole liposome migration as opposed to movement of individual molecules within the liposome, liposome rotation, or fast exchange between lecithin molecules in solution and in vesicles.

Theory of Transport of Long Polymer Molecules through Carbon Nanotube Channels

NASA Technical Reports Server (NTRS)

Wei, Chenyu; Srivastava, Deepak

2003-01-01

A theory of transport of long chain polymer molecules through carbon nanotube (CNT) channels is developed using Fokker-Planck equation and direct molecular dynamics (MD) simulations. The mean transport or translocation time tau is found to depend on the chemical potential energy, entropy and diffusion coefficient. A power law dependence tau approx. N(sup 2)is found where N is number of monomers in a molecule. For 10(exp 5)-unit long polyethylene molecules, tau is estimated to be approx. 1micro-s. The diffusion coefficient of long polymer molecules inside CNTs, like that of short ones, are found to be few orders of magnitude larger than in ordinary silicate based zeolite systems.

Jump rates for surface diffusion of large molecules from first principles

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

Shea, Patrick, E-mail: patrick.shea@dal.ca; Kreuzer, Hans Jürgen

2015-04-21

We apply a recently developed stochastic model for the surface diffusion of large molecules to calculate jump rates for 9,10-dithioanthracene on a Cu(111) surface. The necessary input parameters for the stochastic model are calculated from first principles using density functional theory (DFT). We find that the inclusion of van der Waals corrections to the DFT energies is critical to obtain good agreement with experimental results for the adsorption geometry and energy barrier for diffusion. The predictions for jump rates in our model are in excellent agreement with measured values and show a marked improvement over transition state theory (TST). Wemore » find that the jump rate prefactor is reduced by an order of magnitude from the TST estimate due to frictional damping resulting from energy exchange with surface phonons, as well as a rotational mode of the diffusing molecule.« less

Simulation of stochastic diffusion via first exit times

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

Lötstedt, Per, E-mail: perl@it.uu.se; Meinecke, Lina, E-mail: lina.meinecke@it.uu.se

2015-11-01

In molecular biology it is of interest to simulate diffusion stochastically. In the mesoscopic model we partition a biological cell into unstructured subvolumes. In each subvolume the number of molecules is recorded at each time step and molecules can jump between neighboring subvolumes to model diffusion. The jump rates can be computed by discretizing the diffusion equation on that unstructured mesh. If the mesh is of poor quality, due to a complicated cell geometry, standard discretization methods can generate negative jump coefficients, which no longer allows the interpretation as the probability to jump between the subvolumes. We propose a methodmore » based on the mean first exit time of a molecule from a subvolume, which guarantees positive jump coefficients. Two approaches to exit times, a global and a local one, are presented and tested in simulations on meshes of different quality in two and three dimensions.« less

Simulation of stochastic diffusion via first exit times

PubMed Central

Lötstedt, Per; Meinecke, Lina

2015-01-01

In molecular biology it is of interest to simulate diffusion stochastically. In the mesoscopic model we partition a biological cell into unstructured subvolumes. In each subvolume the number of molecules is recorded at each time step and molecules can jump between neighboring subvolumes to model diffusion. The jump rates can be computed by discretizing the diffusion equation on that unstructured mesh. If the mesh is of poor quality, due to a complicated cell geometry, standard discretization methods can generate negative jump coefficients, which no longer allows the interpretation as the probability to jump between the subvolumes. We propose a method based on the mean first exit time of a molecule from a subvolume, which guarantees positive jump coefficients. Two approaches to exit times, a global and a local one, are presented and tested in simulations on meshes of different quality in two and three dimensions. PMID:26600600

Quantum fluctuations increase the self-diffusive motion of para-hydrogen in narrow carbon nanotubes.

PubMed

Kowalczyk, Piotr; Gauden, Piotr A; Terzyk, Artur P; Furmaniak, Sylwester

2011-05-28

Quantum fluctuations significantly increase the self-diffusive motion of para-hydrogen adsorbed in narrow carbon nanotubes at 30 K comparing to its classical counterpart. Rigorous Feynman's path integral calculations reveal that self-diffusive motion of para-hydrogen in a narrow (6,6) carbon nanotube at 30 K and pore densities below ∼29 mmol cm(-3) is one order of magnitude faster than the classical counterpart. We find that the zero-point energy and tunneling significantly smoothed out the free energy landscape of para-hydrogen molecules adsorbed in a narrow (6,6) carbon nanotube. This promotes a delocalization of the confined para-hydrogen at 30 K (i.e., population of unclassical paths due to quantum effects). Contrary the self-diffusive motion of classical para-hydrogen molecules in a narrow (6,6) carbon nanotube at 30 K is very slow. This is because classical para-hydrogen molecules undergo highly correlated movement when their collision diameter approached the carbon nanotube size (i.e., anomalous diffusion in quasi-one dimensional pores). On the basis of current results we predict that narrow single-walled carbon nanotubes are promising nanoporous molecular sieves being able to separate para-hydrogen molecules from mixtures of classical particles at cryogenic temperatures. This journal is © the Owner Societies 2011

Developing a model of plant hormone interactions

PubMed Central

Wang, Yu Hua

2011-01-01

Plant growth and development is influenced by mutual interactions among plant hormones. The five classical plant hormones are auxins, cytokinins, gibberellins, abscisic acid and ethylene. They are small diffusible molecules that easily penetrate between cells. In addition, newer classes of plant hormones have been identified such as brassinosteroids, jasmonic acid, salicylic acid and various small proteins or peptides. These hormones also play important roles in the regulation of plant growth and development. This review begins with a brief summary of the current findings on plant hormones. Based on this knowledge, a conceptual model about interactions among plant hormones is built so as to link and develop an understanding of the diverse functions of different plant hormones as a whole in plants. PMID:21406974

Transition paths in single-molecule force spectroscopy

NASA Astrophysics Data System (ADS)

Cossio, Pilar; Hummer, Gerhard; Szabo, Attila

2018-03-01

In a typical single-molecule force spectroscopy experiment, the ends of the molecule of interest are connected by long polymer linkers to a pair of mesoscopic beads trapped in the focus of two laser beams. At constant force load, the total extension, i.e., the end-to-end distance of the molecule plus linkers, is measured as a function of time. In the simplest systems, the measured extension fluctuates about two values characteristic of folded and unfolded states, with occasional transitions between them. We have recently shown that molecular (un)folding rates can be recovered from such trajectories, with a small linker correction, as long as the characteristic time of the bead fluctuations is shorter than the residence time in the unfolded (folded) state. Here, we show that accurate measurements of the molecular transition path times require an even faster apparatus response. Transition paths, the trajectory segments in which the molecule (un)folds, are properly resolved only if the beads fluctuate more rapidly than the end-to-end distance of the molecule. Therefore, over a wide regime, the measured rates may be meaningful but not the transition path times. Analytic expressions for the measured mean transition path times are obtained for systems diffusing anisotropically on a two-dimensional free energy surface. The transition path times depend on the properties both of the molecule and of the pulling device.

Probing Biomolecular Structures and Dynamics of Single Molecules Using In-Gel Alternating-Laser Excitation

PubMed Central

Santoso, Yusdi; Kapanidis, Achillefs N.

2009-01-01

Gel electrophoresis is a standard biochemical technique used for separating biomolecules on the basis of size and charge. Despite the use of gels in early single-molecule experiments, gel electrophoresis has not been widely adopted for single-molecule fluorescence spectroscopy. We present a novel method that combines gel electrophoresis and single-molecule fluorescence spectroscopy to simultaneously purify and analyze biomolecules in a gel matrix. Our method, in-gel ALEX, uses non-denaturing gels to purify biomolecular complexes of interest from free components, aggregates, and non-specific complexes. The gel matrix also slows down translational diffusion of molecules, giving rise to long, high-resolution time traces without surface immobilization, which allow extended observations of conformational dynamics in a biologically friendly environment. We demonstrated the compatibility of this method with different types of single molecule spectroscopy techniques, including confocal detection and fluorescence-correlation spectroscopy. We demonstrated that in-gel ALEX can be used to study conformational dynamics at the millisecond timescale; by studying a DNA hairpin in gels, we directly observed fluorescence fluctuations due to conformational interconversion between folded and unfolded states. Our method is amenable to the addition of small molecules that can alter the equilibrium and dynamic properties of the system. In-gel ALEX will be a versatile tool for studying structures and dynamics of complex biomolecules and their assemblies. PMID:19863108

Enhanced Light Absorption in Fluorinated Ternary Small-Molecule Photovoltaics

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

Eastham, Nicholas D.; Dudnik, Alexander S.; Harutyunyan, Boris

2017-06-14

Using small-molecule donor (SMD) semiconductors in organic photovoltaics (OPVs) has historically afforded lower power conversion efficiencies (PCEs) than their polymeric counterparts. The PCE difference is attributed to shorter conjugated backbones, resulting in reduced intermolecular interactions. Here, a new pair of SMDs is synthesized based on the diketopyrrolopyrrole-benzodithiophene-diketopyrrolopyrrole (BDT-DPP2) skeleton but having fluorinated and fluorinefree aromatic side-chain substituents. Ternary OPVs having varied ratios of the two SMDs with PC61BM as the acceptor exhibit tunable open-circuit voltages (Vocs) between 0.833 and 0.944 V due to a fluorination-induced shift in energy levels and the electronic “alloy” formed from the miscibility of the twomore » SMDs. A 15% increase in PCE is observed at the optimal ternary SMD ratio, with the short-circuit current density (Jsc) significantly increased to 9.18 mA/cm2. The origin of Jsc enhancement is analyzed via charge generation, transport, and diffuse reflectance measurements, and is attributed to increased optical absorption arising from a maximum in film crystallinity at this SMD ratio, observed by grazing incidence wide-angle X-ray scattering.« less

Ultra-small dye-doped silica nanoparticles via modified sol-gel technique

NASA Astrophysics Data System (ADS)

Riccò, R.; Nizzero, S.; Penna, E.; Meneghello, A.; Cretaio, E.; Enrichi, F.

2018-05-01

In modern biosensing and imaging, fluorescence-based methods constitute the most diffused approach to achieve optimal detection of analytes, both in solution and on the single-particle level. Despite the huge progresses made in recent decades in the development of plasmonic biosensors and label-free sensing techniques, fluorescent molecules remain the most commonly used contrast agents to date for commercial imaging and detection methods. However, they exhibit low stability, can be difficult to functionalise, and often result in a low signal-to-noise ratio. Thus, embedding fluorescent probes into robust and bio-compatible materials, such as silica nanoparticles, can substantially enhance the detection limit and dramatically increase the sensitivity. In this work, ultra-small fluorescent silica nanoparticles (NPs) for optical biosensing applications were doped with a fluorescent dye, using simple water-based sol-gel approaches based on the classical Stöber procedure. By systematically modulating reaction parameters, controllable size tuning of particle diameters as low as 10 nm was achieved. Particles morphology and optical response were evaluated showing a possible single-molecule behaviour, without employing microemulsion methods to achieve similar results. [Figure not available: see fulltext.

NMReDATA, a standard to report the NMR assignment and parameters of organic compounds.

PubMed

Pupier, Marion; Nuzillard, Jean-Marc; Wist, Julien; Schlörer, Nils E; Kuhn, Stefan; Erdelyi, Mate; Steinbeck, Christoph; Williams, Antony J; Butts, Craig; Claridge, Tim D W; Mikhova, Bozhana; Robien, Wolfgang; Dashti, Hesam; Eghbalnia, Hamid R; Farès, Christophe; Adam, Christian; Kessler, Pavel; Moriaud, Fabrice; Elyashberg, Mikhail; Argyropoulos, Dimitris; Pérez, Manuel; Giraudeau, Patrick; Gil, Roberto R; Trevorrow, Paul; Jeannerat, Damien

2018-04-14

Even though NMR has found countless applications in the field of small molecule characterization, there is no standard file format available for the NMR data relevant to structure characterization of small molecules. A new format is therefore introduced to associate the NMR parameters extracted from 1D and 2D spectra of organic compounds to the proposed chemical structure. These NMR parameters, which we shall call NMReDATA (for nuclear magnetic resonance extracted data), include chemical shift values, signal integrals, intensities, multiplicities, scalar coupling constants, lists of 2D correlations, relaxation times, and diffusion rates. The file format is an extension of the existing Structure Data Format, which is compatible with the commonly used MOL format. The association of an NMReDATA file with the raw and spectral data from which it originates constitutes an NMR record. This format is easily readable by humans and computers and provides a simple and efficient way for disseminating results of structural chemistry investigations, allowing automatic verification of published results, and for assisting the constitution of highly needed open-source structural databases. Copyright © 2018 John Wiley & Sons, Ltd.

Degradation of small-molecule organic solar cells

NASA Astrophysics Data System (ADS)

Song, Q. L.; Wang, M. L.; Obbard, E. G.; Sun, X. Y.; Ding, X. M.; Hou, X. Y.; Li, C. M.

2006-12-01

Small-molecule organic solar cells with a structure of indium tin oxide (ITO)tris-8-hydroxy-quinolinato aluminum (Alq3) (2nm)fullerene (C60) (40nm)\\copper phthalocyanine (CuPc) (32nm)Au (40nm) were fabricated. The shelf lifetime of unencapsulated devices was over 1500h, and the power conversion efficiency reached 0.76% under AM1.5G (air mass 1.5 global) 75mW/cm2. The long lifetime was attributed to the inverted structure compared to the conventional ITO CuPcC60bufferAl structure since the former could effectively protect C60 from the diffusion of oxygen and modify interfacial electrical properties. The introduction of a 2nm Alq3 layer into the cells enhanced the power conversion efficiency by more than 20 times. The presence of the thin Alq3 film on the ITO substrate lowered the substrate work function and hence increased the electric field in the organic layers, which was beneficial to the collection of free carriers. The reasons for the degradation of such kind of organic solar cells are analyzed in detail.

Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo.

PubMed

Gullbrand, Sarah E; Peterson, Joshua; Mastropolo, Rosemarie; Roberts, Timothy T; Lawrence, James P; Glennon, Joseph C; DiRisio, Darryl J; Ledet, Eric H

2015-05-01

The intervertebral disc primarily relies on trans-endplate diffusion for the uptake of nutrients and the clearance of byproducts. In degenerative discs, diffusion is often diminished by endplate sclerosis and reduced proteoglycan content. Mechanical loading-induced convection has the potential to augment diffusion and enhance net transport into the disc. The ability of convection to augment disc transport is controversial and has not been demonstrated in vivo. To determine if loading-induced convection can enhance small molecule transport into the intervertebral disc in vivo. Net transport was quantified via postcontrast enhanced magnetic resonance imaging (MRI) into the discs of the New Zealand white rabbit lumbar spine subjected to in vivo cyclic low rate loading. Animals were administered the MRI contrast agent gadodiamide intravenously and subjected to in vivo low rate loading (0.5 Hz, 200 N) via a custom external loading apparatus for either 2.5, 5, 10, 15, or 20 minutes. Animals were then euthanized and the lumbar spines imaged using postcontrast enhanced MRI. The T1 constants in the nucleus, annulus, and cartilage endplates were quantified as a measure of gadodiamide transport into the loaded discs compared with the adjacent unloaded discs. Microcomputed tomography was used to quantify subchondral bone density. Low rate loading caused the rapid uptake and clearance of gadodiamide in the nucleus compared with unloaded discs, which exhibited a slower rate of uptake. Relative to unloaded discs, low rate loading caused a maximum increase in transport into the nucleus of 16.8% after 5 minutes of loading. Low rate loading increased the concentration of gadodiamide in the cartilage endplates at each time point compared with unloaded levels. Results from this study indicate that forced convection accelerated small molecule uptake and clearance in the disc induced by low rate mechanical loading. Low rate loading may, therefore, be therapeutic to the disc as it may enhance the nutrient uptake and waste product clearance. Copyright © 2015 Elsevier Inc. All rights reserved.

Extensive database of liquid phase diffusion coefficients of some frequently used test molecules in reversed-phase liquid chromatography and hydrophilic interaction liquid chromatography.

PubMed

Song, Huiying; Vanderheyden, Yoachim; Adams, Erwin; Desmet, Gert; Cabooter, Deirdre

2016-07-15

Diffusion plays an important role in all aspects of band broadening in chromatography. An accurate knowledge of molecular diffusion coefficients in different mobile phases is therefore crucial in fundamental column performance studies. Correlations available in literature, such as the Wilke-Chang equation, can provide good approximations of molecular diffusion under reversed-phase conditions. However, these correlations have been demonstrated to be less accurate for mobile phases containing a large percentage of acetonitrile, as is the case in hydrophilic interaction liquid chromatography. A database of experimentally measured molecular diffusion coefficients of some 45 polar and apolar compounds that are frequently used as test molecules under hydrophilic interaction liquid chromatography and reversed-phase conditions is therefore presented. Special attention is given to diffusion coefficients of polar compounds obtained in large percentages of acetonitrile (>90%). The effect of the buffer concentration (5-10mM ammonium acetate) on the obtained diffusion coefficients is investigated and is demonstrated to mainly influence the molecular diffusion of charged molecules. Diffusion coefficients are measured using the Taylor-Aris method and hence deduced from the peak broadening of a solute when flowing through a long open tube. The validity of the set-up employed for the measurement of the diffusion coefficients is demonstrated by ruling out the occurrence of longitudinal diffusion, secondary flow interactions and extra-column effects, while it is also shown that radial equilibration in the 15m long capillary is effective. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of straight, unconnected, radially-oriented, and tapered mesopores on column efficiency: A theoretical investigation.

PubMed

Gritti, Fabrice

2017-02-17

Superficially porous particles (SPPs) can be prepared from a pseudomorphic transformation (PMT) which produces straight, unconnected, and radially-oriented mesopores (ROMs). ROMs can be either both ends open in fully porous particles (FPPs) or one-end-closed in SPPs. The impact of ROMs on the longitudinal diffusion (B/u), solid-liquid mass transfer resistance (C s u), and on the eddy dispersion (A(u)) height equivalent to a theoretical plate (HETP) of 3D randomly packed columns was investigated based on theoretical viewpoints. Torquato's theory of effective diffusion in packed beds (B term), Giddings' coupling theory of eddy dispersion (A term), and Giddings' generalized nonequilibrium theory (C s term) are applied to make predictions. First, it is found that the A term is nearly independent on the internal structure of the particle. Secondly, in the absence of flow, infinitely narrow and both ends open (no constriction effect) ROMs induce an internal hindrance factor of 23 regarding diffusion along the axial direction. Experimental data reveal that one-end-closed and 80Å wide ROMs in SPPs lead to a measurable internal hindrance factor of 27 regarding diffusion in the porous shell. Thirdly, above the optimum speed, the C s coefficient is dependent on the geometry (cylinders, cones, etc.) of the ROMs: when ROMs are conical in SPPs, C s is expected to decrease by 80% with respect to cylindrical ROMs. From an application perspective, PMT-SPPs prepared with narrow ROMs are well suited for the analysis of small molecules at or below optimum speed (lowest B term) while PMT-SPPs made of wide and conical ROMs are ideal for the analysis of large molecules above optimum speed (smallest C s term). Copyright © 2017. Published by Elsevier B.V.

A New View of the Bacterial Cytosol Environment

PubMed Central

Cossins, Benjamin P.; Jacobson, Matthew P.; Guallar, Victor

2011-01-01

The cytosol is the major environment in all bacterial cells. The true physical and dynamical nature of the cytosol solution is not fully understood and here a modeling approach is applied. Using recent and detailed data on metabolite concentrations, we have created a molecular mechanical model of the prokaryotic cytosol environment of Escherichia coli, containing proteins, metabolites and monatomic ions. We use 200 ns molecular dynamics simulations to compute diffusion rates, the extent of contact between molecules and dielectric constants. Large metabolites spend ∼80% of their time in contact with other molecules while small metabolites vary with some only spending 20% of time in contact. Large non-covalently interacting metabolite structures mediated by hydrogen-bonds, ionic and π stacking interactions are common and often associate with proteins. Mg2+ ions were prominent in NIMS and almost absent free in solution. Κ+ is generally not involved in NIMSs and populates the solvent fairly uniformly, hence its important role as an osmolyte. In simulations containing ubiquitin, to represent a protein component, metabolite diffusion was reduced owing to long lasting protein-metabolite interactions. Hence, it is likely that with larger proteins metabolites would diffuse even more slowly. The dielectric constant of these simulations was found to differ from that of pure water only through a large contribution from ubiquitin as metabolite and monatomic ion effects cancel. These findings suggest regions of influence specific to particular proteins affecting metabolite diffusion and electrostatics. Also some proteins may have a higher propensity for associations with metabolites owing to their larger electrostatic fields. We hope that future studies may be able to accurately predict how binding interactions differ in the cytosol relative to dilute aqueous solution. PMID:21695225

Optimized green fluorescent protein fused to FoF1-ATP synthase for single-molecule FRET using a fast anti-Brownian electrokinetic trap

NASA Astrophysics Data System (ADS)

Dienerowitz, Maria; Ilchenko, Mykhailo; Su, Bertram; Deckers-Hebestreit, Gabriele; Mayer, Günter; Henkel, Thomas; Heitkamp, Thomas; Börsch, Michael

2016-02-01

Observation times of freely diffusing single molecules in solution are limited by the photophysics of the attached fluorescence markers and by a small observation volume in the femtolitre range that is required for a sufficient signal-to-background ratio. To extend diffusion-limited observation times through a confocal detection volume, A. E. Cohen and W. E. Moerner have invented and built the ABELtrap -- a microfluidic device to actively counteract Brownian motion of single nanoparticles with an electrokinetic trap. Here we present a version of an ABELtrap with a laser focus pattern generated by electro-optical beam deflectors and controlled by a programmable FPGA chip. This ABELtrap holds single fluorescent nanoparticles for more than 100 seconds, increasing the observation time of fluorescent nanoparticles compared to free diffusion by a factor of 10000. To monitor conformational changes of individual membrane proteins in real time, we record sequential distance changes between two specifically attached dyes using Förster resonance energy transfer (smFRET). Fusing the a-subunit of the FoF1-ATP synthase with mNeonGreen results in an improved signal-to-background ratio at lower laser excitation powers. This increases our measured trap duration of proteoliposomes beyond 2 s. Additionally, we observe different smFRET levels attributed to varying distances between the FRET donor (mNeonGreen) and acceptor (Alexa568) fluorophore attached at the a- and c-subunit of the FoF1-ATP synthase respectively.

The effect of macromolecular crowding on the structure of the protein complex superoxide dismutase

NASA Astrophysics Data System (ADS)

Rajapaksha Mudalige, Ajith Rathnaweera

Biological environments contain between 7 - 40% macromolecules by volume. This reduces the available volume for macromolecules and elevates the osmotic pressure relative to pure water. Consequently, biological macromolecules in their native environments tend to adopt more compact and dehydrated conformations than those in vitro. This effect is referred to as macromolecular crowding and constitutes an important physical difference between native biological environments and the simple solutions in which biomolecules are usually studied. We used small angle scattering (SAS) to measure the effects of macromolecular crowding on the size of a protein complex, superoxide dismutase (SOD). Crowding was induced using 400 MW polyethylene glycol (PEG), triethylene glycol (TEG), methyl-alpha-glucoside (alpha-MG) and trimethylamine N-oxide (TMAO). Parallel small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) allowed us to unambiguously attribute apparent changes in radius of gyration to changes in the structure of SOD. For a 40% PEG solution, we find that the volume of SOD was reduced by 9%. SAS coupled with osmotic pressure measurements allowed us to estimate a compressibility modulus for SOD. We believe this to be the first time the osmotic compressibility of a protein complex was measured. Molecular Dynamics (MD) simulations are widely used to obtain insights on biomolecular processes. However, it is not clear whether MD is capable of predicting subtle effects of macromolecular crowding. We used our experimentally observed compressibility of SOD to evaluate the ability of MD to predict macromolecular crowding. Effects of macromolecular crowding due to PEG on SOD were modeled using an all atom MD simulation with the CHARMM forcefield and the crystallographically resolved structures of SOD and PEG. Two parallel MD simulations were performed for SOD in water and SOD in 40% PEG for over 150~ns. Over the period of the simulation the SOD structure in 40% PEG did not change compared to the SOD structure in water. It therefore appears that under the conditions of our simulations MD could not describe the experimentally observed effects of macromolecular crowding. In a separate project, we measured the rate of diffusive transport in excised porcine corneal stroma using FCS for fluorescent labeled dextran molecules with hydrodynamic radii ranging from 1.3 to 34 nm. Dextran molecules diffuse more slowly in cornea as compared to buffer solution. The reduction in diffusion coefficient is modest however (67% smaller), and is uniform over the range of sizes that we measured. Diffusion coefficients measured parallel vs. perpendicular to the collagen lamellae were indistinguishable. This indicates that diffusion in the corneal stroma is not highly anisotropic. Delivery of therapeutic agents to the eye requires efficient transport through cellular and extracellular barriers. Our measurements bring important insights into how macromolecular and nanoparticle therapeutics might permeate through the eyes.

Effects of microwave electric fields on the translational diffusion of dipolar molecules in surface potential: A simulation study

NASA Astrophysics Data System (ADS)

Kapranov, Sergey V.; Kouzaev, Guennadi A.

2018-01-01

Variations of effective diffusion coefficient of polar molecules exposed to microwave electric fields in a surface potential are studied by solving coupled stochastic differential equations of motion with a deterministic component of the surface force. Being an essential tool for the simulation interpretation, a theoretical approach to effective diffusion in surface potential is first developed. The effective diffusion coefficient is represented as the product of the normal diffusion coefficient and potential-dependent correction function, whose temperature dependence is close to the Arrhenius form. The analytically found zero-diffusion condition defines the state of thermal equilibrium at the surface. The diffusion of a water-like dipole molecule in the potential of graphite surface is simulated in the field-free conditions and in the presence of the alternating electric fields of various magnitude intensities and frequencies. Temperature dependence of the correction function exhibits field-induced variations of the effective Lennard-Jones energy parameter. It demonstrates maximum departure from the zero-field value at certain frequencies and intensities, which is associated with variations in the rotational dynamics. A concept of the amplitude-frequency resonance put forward to interpret the simulation results is explained using a heuristic reasoning and is corroborated by semi-quantitative considerations in terms of the Dissado-Hill cluster theory of dielectric relaxation.

Ammonia Diffusion through Nalophan Double Bags: Effect of Concentration Gradient Reduction

PubMed Central

Capelli, Laura; Boiardi, Emanuela; Del Rosso, Renato

2014-01-01

The ammonia loss through Nalophan bags has been studied. The losses observed for storage conditions and times as allowed by the reference standard for dynamic olfactometry (EN 13725:2003) indicate that odour concentration values due to the presence of small molecules may be significantly underestimated if samples are not analysed immediately after sampling. A diffusion model was used in order to study diffusion through the bag. The study discusses the effect of concentration gradient (ΔC) across the polymeric membrane of the analyte. The ΔC was controlled by using a setup bag called “double bags.” Experimental data show a reduction of ammonia percentage losses due to the effect of the external multibarrier. The expedient of the double bag loaded with the same gas mixture allows a reduced diffusion of ammonia into the inner bag. Comparing the inner bag losses with those of the single bag stored in the same conditions (T, P, u) and with equal geometrical characteristics (S/V, z), it was observed that the inner bag of the double bag displays a 16% loss while the single bag displays a 37% loss. Acting on the ΔC it is possible to achieve a gross reduction of 57% in the ammonia leakage due to diffusion. PMID:25506608

Novel surface diffusion characteristics for a robust pentacene derivative on Au(1 1 1) surfaces

NASA Astrophysics Data System (ADS)

Miller, Ryan A.; Larson, Amanda; Pohl, Karsten

2017-06-01

Molecular dynamics simulations have been performed in both the ab initio and classical mechanics frameworks of 5,6,7-trithiapentacene-13-one (TTPO) molecules on flat Au(1 1 1) surfaces. Results show new surface diffusion characteristics including a strong preference for the molecule to align its long axis parallel to the sixfold Au(1 1 1) symmetry directions and subsequently diffuse along these close-packed directions, and a calculated activation energy for diffusion of 0.142 eV, about four times larger than that for pure pentacene on Au. The temperature-dependent diffusion coefficients were calculated to help quantify the molecular mobility during the experimentally observed process of forming self-assembled monolayers on gold electrodes.

Understanding of Relationship between Phospholipid Membrane Permeability and Self-Diffusion Coefficients of Some Drugs and Biologically Active Compounds in Model Solvents.

PubMed

Blokhina, Svetlana V; Volkova, Tatyana V; Golubev, Vasiliy A; Perlovich, German L

2017-10-02

In this work we measured self-diffusion coefficients of 5 drugs (aspirin, caffeine, ethionamide, salicylic acid, and paracetamol) and 11 biologically active compounds of similar structure in deuterated water and 1-octanol by NMR. It has been found that an increase in the van der Waals volume of the molecules of the studied substances result in reduction of their diffusion mobility in both solvents. The analysis of the experimental data showed the influence of chemical nature and structural isomerization of the molecules on the diffusion mobility. Apparent permeability coefficients of the studied compounds were determined using an artificial phospholipid membrane made of egg lecithin as a model of in vivo absorption. Distribution coefficients in 1-octanol/buffer pH 7.4 system were measured. For the first time the model of the passive diffusion through the phospholipid membrane was validated based on the experimental data. To this end, the passive diffusion was considered as an additive process of molecule passage through the aqueous boundary layer before the membrane and 1-octanol barrier simulating the lipid layer of the membrane.

Ordinary differential equations with applications in molecular biology.

PubMed

Ilea, M; Turnea, M; Rotariu, M

2012-01-01

Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances. Ordinary differential equations are used to model biological processes on various levels ranging from DNA molecules or biosynthesis phospholipids on the cellular level.

Exploring Drug Diffusion through a Membrane: A Physical Chemistry Experiment for Health and Life Sciences Undergraduate Students

ERIC Educational Resources Information Center

Ribeiro, Isabel A. C.; Faustino, Ce´lia M. C.; Guedes, Rita C.; Alfaia, Anto´nio J. I.; Ribeiro, Maria H. L.

2015-01-01

The transport of molecules across biological membranes are critical for most cellular processes. Membrane permeability is also a key determinant for drug absorption, distribution, and elimination. Diffusion, that is, the migration of matter down a concentration gradient, is a simple mechanism by which both endogenous and drug molecules can enter…

Lattice Light Sheet Microscopy: Imaging Molecules to Embryos at High Spatiotemporal Resolution

PubMed Central

Chen, Bi-Chang; Legant, Wesley R.; Wang, Kai; Shao, Lin; Milkie, Daniel E.; Davidson, Michael W.; Janetopoulos, Chris; Wu, Xufeng S.; Hammer, John A.; Liu, Zhe; English, Brian P.; Mimori-Kiyosue, Yuko; Romero, Daniel P.; Ritter, Alex T.; Lippincott-Schwartz, Jennifer; Fritz-Laylin, Lillian; Mullins, R. Dyche; Mitchell, Diana M.; Bembenek, Joshua N.; Reymann, Anne-Cecile; Böhme, Ralph; Grill, Stephan W.; Wang, Jennifer T.; Seydoux, Geraldine; Tulu, U. Serdar; Kiehart, Daniel P.; Betzig, Eric

2015-01-01

Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, too small, or occur too rapidly to see clearly with existing tools. We crafted ultra-thin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at sub-second intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. The results provide a visceral reminder of the beauty and complexity of living systems. PMID:25342811

Molecular Diffusion in Plasma Membranes of Primary Lymphocytes Measured by Fluorescence Correlation Spectroscopy.

PubMed

Staaf, Elina; Bagawath-Singh, Sunitha; Johansson, Sofia

2017-02-01

Fluorescence correlation spectroscopy (FCS) is a powerful technique for studying the diffusion of molecules within biological membranes with high spatial and temporal resolution. FCS can quantify the molecular concentration and diffusion coefficient of fluorescently labeled molecules in the cell membrane. This technique has the ability to explore the molecular diffusion characteristics of molecules in the plasma membrane of immune cells in steady state (i.e., without processes affecting the result during the actual measurement time). FCS is suitable for studying the diffusion of proteins that are expressed at levels typical for most endogenous proteins. Here, a straightforward and robust method to determine the diffusion rate of cell membrane proteins on primary lymphocytes is demonstrated. An effective way to perform measurements on antibody-stained live cells and commonly occurring observations after acquisition are described. The recent advancements in the development of photo-stable fluorescent dyes can be utilized by conjugating the antibodies of interest to appropriate dyes that do not bleach extensively during the measurements. Additionally, this allows for the detection of slowly diffusing entities, which is a common feature of proteins expressed in cell membranes. The analysis procedure to extract molecular concentration and diffusion parameters from the generated autocorrelation curves is highlighted. In summary, a basic protocol for FCS measurements is provided; it can be followed by immunologists with an understanding of confocal microscopy but with no other previous experience of techniques for measuring dynamic parameters, such as molecular diffusion rates.

Diffusion through Pig Gastric Mucin: Effect of Relative Humidity

PubMed Central

Runnsjö, Anna; Dabkowska, Aleksandra P.; Sparr, Emma; Kocherbitov, Vitaly; Arnebrant, Thomas; Engblom, Johan

2016-01-01

Mucus covers the epithelium found in all intestinal tracts, where it serves as an important protecting barrier, and pharmaceutical drugs administrated by the oral, rectal, vaginal, ocular, or nasal route need to penetrate the mucus in order to reach their targets. Furthermore, the diffusion in mucus as well as the viscosity of mucus in the eyes, nose and throat can change depending on the relative humidity of the surrounding air. In this study we have investigated how diffusion through gels of mucin, the main protein in mucus, is affected by changes in ambient relative humidity (i.e. water activity). Already a small decrease in water activity was found to give rise to a significant decrease in penetration rate through the mucin gel of the antibacterial drug metronidazole. We also show that a decrease in water activity leads to decreased diffusion rate in the mucin gel for the fluorophore fluorescein. This study shows that it is possible to alter transport rates of molecules through mucus by changing the water activity in the gel. It furthermore illustrates the importance of considering effects of the water activity in the mucosa during development of potential pharmaceuticals. PMID:27336158

Controlling molecular condensation/diffusion of copper phthalocyanine by local electric field induced with scanning tunneling microscope tip

NASA Astrophysics Data System (ADS)

Nagaoka, Katsumi; Yaginuma, Shin; Nakayama, Tomonobu

2018-02-01

We have discovered the condensation/diffusion phenomena of copper phthalocyanine (CuPc) molecules controlled with a pulsed electric field induced by the scanning tunneling microscope tip. This behavior is not explained by the conventional induced dipole model. In order to understand the mechanism, we have measured the electronic structure of the molecule by tunneling spectroscopy and also performed theoretical calculations on molecular orbitals. These data clearly indicate that the molecule is positively charged owing to charge transfer to the substrate, and that hydrogen bonding exists between CuPc molecules, which makes the molecular island stable.

Nuclear magnetic resonance relaxation and diffusion measurements as a proxy for soil properties

NASA Astrophysics Data System (ADS)

Duschl, Markus; Pohlmeier, Andreas; Galvosas, Petrik; Vereecken, Harry

2013-04-01

Nuclear Magnetic Resonance (NMR) relaxation and NMR diffusion measurements are two of a series of fast and non-invasive NMR applications widely used e.g. as well logging tools in petroleum exploration [1]. For experiments with water, NMR relaxation measures the relaxation behaviour of former excited water molecules, and NMR diffusion evaluates the self-diffusion of water. Applied in porous media, both relaxation and diffusion measurements depend on intrinsic properties of the media like pore size distribution, connectivity and tortuosity of the pores, and water saturation [2, 3]. Thus, NMR can be used to characterise the pore space of porous media not only in consolidated sediments but also in soil. The physical principle behind is the relaxation of water molecules in an external magnetic field after excitation. In porous media water molecules in a surface layer of the pores relax faster than the molecules in bulk water because of interactions with the pore wall. Thus, the relaxation in smaller pores is generally faster than in bigger pores resulting in a relaxation time distribution for porous media with a range of pore sizes like soil [4]. In NMR diffusion experiments, there is an additional encoding of water molecules by application of a magnetic field gradient. Subsequent storage of the magnetization and decoding enables the determination of the mean square displacement and therefore of the self-diffusion of the water molecules [5]. Employing various relaxation and diffusion experiments, we get a measure of the surface to volume ratio of the pores and the tortuosity of the media. In this work, we show the characterisation of a set of sand and soil samples covering a wide range of textural classes by NMR methods. Relaxation times were monitored by the Carr-Purcell-Meiboom-Gill sequence and analysed using inverse Laplace transformation. Apparent self-diffusion constants were detected by a 13-intervall pulse sequence and variation of the storage time. We correlated the results with various soil properties like texture, water retention parameters, and hydraulic conductivity. This way we show that we can predict soil properties by NMR measurements and that we are able use results of NMR measurements as a proxy without the need of direct measurements. [1] Song, Y.-Q., Vadose Zone Journal, 9 (2010) [2] Stingaciu, L. R., et al., Water Resources Research, 46 (2010) [3] Vogt, C., et al., Journal of Applied Geophysics, 50 (2002) [4] Barrie, P. J., Annual Reports on NMR Spectroscopy, 41 (2000) [5] Stallmach, F., Galvosas, P., Annual Reports on NMR Spectroscopy, 61 (2007)

Effect of seawater salinity on pore-size distribution on a poly(styrene)-based HP20 resin and its adsorption of diarrhetic shellfish toxins.

PubMed

Fan, Lin; Sun, Geng; Qiu, Jiangbing; Ma, Qimin; Hess, Philipp; Li, Aifeng

2014-12-19

In the present study, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were spiked into artificial seawater at low, medium and high estuarine salinities (9‰, 13.5‰ and 27‰). Passive samplers (HP20 resin) used for solid phase adsorption toxin tracking (SPATT) technology were exposed in these seawaters for 12-h periods. Adsorption curves well fitted a pseudo-secondary kinetics model. The highest initial sorption rates of both toxins occurred in the seawater of medium salinity, followed by seawater of low and high estuarine salinity. Pore volumes of micropores (<2 nm) and small mesopores (2 nm

Diffusion of a Highly-Charged Supramolecular Assembly: Direct Observation of Ion-Association in Water

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

University of California, Berkeley; Lawrence Berkeley National Laboratory; Raymond, Kenneth

2007-10-22

Understanding the solution behavior of supramolecular assemblies is essential for a full understanding of the formation and chemistry of synthetic host-guest systems. While the interaction between host and guest molecules is generally the focus of mechanistic studies of host-guest complexes, the interaction of the host-guest complex with other species in solution remains largely unknown, although in principle accessible by diffusion studies. Several NMR techniques are available to monitor diffusion and have recently been reviewed. Pulsed gradient spin-echo (PGSE) NMR methods have attracted increasing interest, since they allow diffusion coefficients to be measured with high accuracy; they have been successfully usedmore » with observation of {sup 7}Li and {sup 31}P nuclei as well as with {sup 1}H NMR. We report here the direct measurement of diffusion coefficients to observe ion-association interactions by counter cations with a highly-charged supramolecular assembly. Raymond and coworkers have described the design and chemistry of a class of metal-ligand supramolecular assemblies over the past decade. The [Ga{sub 4}L{sub 6}]{sup 12-} (L = 1,5-bis(2,3-dihydroxybenzamido)naphthalene) (1) (Figure 1) assembly has garnered the most attention, with the exploration of the dynamics and mechanism of guest exchange as well as the ability of 1 to achieve either stoichiometric or catalytic reactions inside its interior cavity. Recent studies have revealed the importance of counter cations in solution on the chemistry of 1. During the mechanistic study of the C-H bond activation of aldehydes by [Cp*Ir(PMe{sub 3})(olefin){sup +} {contained_in} 1]{sup 11-} a stepwise guest dissociation mechanism with an ion-paired intermediate was proposed. Similarly, in the mechanism for the hydrolysis of iminium cations generated from the 3-aza Cope rearrangement of enammonium cations in 1, the presence of an exterior ion association was part of the kinetic model. To further substantiate the indirect kinetic evidence for such ion-paired species, we sought to explore the solution behavior of 1 by studying the diffusion of 1 with varying alkali and tetraalkyl ammonium cations. For large molecules in solution, such as synthetic supramolecular assemblies, the diffusion behavior of host and guest molecules can provide valuable information on host-guest interaction. One characteristic feature of a stable host-guest complex is that the host and guest molecules diffuse at the same rate in solution; this has been observed in a number of supramolecular systems. In order to confirm that this system was suitable for study by diffusion NMR spectroscopy, a PGSE-DOSY spectrum was acquired of [NEt{sub 4} {contained_in} 1]{sup 11-} (Figure 2), which shows that the host and guest molecules diffuse at the same rate. Quantitative analysis of the data, from monitoring the integral of host and guest resonances as a function of applied gradient strength, gave identical diffusion coefficients, confirming that the host and guest molecules diffuse together.« less

Transient dichroism in photoreceptor membranes indicates that stable oligomers of rhodopsin do not form during excitation.

PubMed Central

Downer, N W; Cone, R A

1985-01-01

If a photoexcited rhodopsin molecule initiates the formation of rhodopsin oligomers during the process of visual excitation, the rate of rotational diffusion of the rhodopsin molecules involved should change markedly. Using microsecond-flash photometry, we have observed the rotational diffusion of rhodopsin throughout the time period of visual excitation and found that no detectable change occurs in its rotational diffusion rate. Partial chemical cross-linking of the retina yields oligomers of rhodopsin and causes a significant decrease in the rotational diffusion rate of rhodopsin even when as little as 20% of rhodopsin is dimeric. Moreover, the pattern of oligomers formed by cross-linking, taken together with the magnitude of decreases in rotational diffusion rate accompanying the cross-linking reaction, suggests that rhodopsin is a monomer in the dark-adapted state. The experiments reported here show that photoexcited rhodopsin molecules do not irreversibly associate with unbleached neighbors during the time course of the receptor response. Hence, it is not likely that stable oligomers of rhodopsin trigger the excitation of the photoreceptor cell. Images FIGURE 1 PMID:3919778

Fluorescence imaging of single-molecule retention trajectories in reversed-phase chromatographic particles.

PubMed

Cooper, Justin T; Peterson, Eric M; Harris, Joel M

2013-10-01

Due to its high specific surface area and chemical stability, porous silica is used as a support structure in numerous applications, including heterogeneous catalysis, biomolecule immobilization, sensors, and liquid chromatography. Reversed-phase liquid chromatography (RPLC), which uses porous silica support particles, has become an indispensable separations tool in quality control, pharmaceutics, and environmental analysis requiring identification of compounds in mixtures. For complex samples, the need for higher resolution separations requires an understanding of the time scale of processes responsible for analyte retention in the stationary phase. In the present work, single-molecule fluorescence imaging is used to observe transport of individual molecules within RPLC porous silica particles. This technique allows direct measurement of intraparticle molecular residence times, intraparticle diffusion rates, and the spatial distribution of molecules within the particle. On the basis of the localization uncertainty and characteristic measured diffusion rates, statistical criteria were developed to resolve the frame-to-frame behavior of molecules into moving and stuck events. The measured diffusion coefficient of moving molecules was used in a Monte Carlo simulation of a random-walk model within the cylindrical geometry of the particle diameter and microscope depth-of-field. The simulated molecular transport is in good agreement with the experimental data, indicating transport of moving molecules in the porous particle is described by a random-walk. Histograms of stuck-molecule event times, locations, and their contributions to intraparticle residence times were also characterized.

Ultra-small dye-doped silica nanoparticles via modified sol-gel technique.

PubMed

Riccò, R; Nizzero, S; Penna, E; Meneghello, A; Cretaio, E; Enrichi, F

2018-01-01

In modern biosensing and imaging, fluorescence-based methods constitute the most diffused approach to achieve optimal detection of analytes, both in solution and on the single-particle level. Despite the huge progresses made in recent decades in the development of plasmonic biosensors and label-free sensing techniques, fluorescent molecules remain the most commonly used contrast agents to date for commercial imaging and detection methods. However, they exhibit low stability, can be difficult to functionalise, and often result in a low signal-to-noise ratio. Thus, embedding fluorescent probes into robust and bio-compatible materials, such as silica nanoparticles, can substantially enhance the detection limit and dramatically increase the sensitivity. In this work, ultra-small fluorescent silica nanoparticles (NPs) for optical biosensing applications were doped with a fluorescent dye, using simple water-based sol-gel approaches based on the classical Stöber procedure. By systematically modulating reaction parameters, controllable size tuning of particle diameters as low as 10 nm was achieved. Particles morphology and optical response were evaluated showing a possible single-molecule behaviour, without employing microemulsion methods to achieve similar results. Graphical abstractWe report a simple, cheap, reliable protocol for the synthesis and systematic tuning of ultra-small (< 10 nm) dye-doped luminescent silica nanoparticles.

Extracting quantitative measures from EAP: a small clinical study using BFOR.

PubMed

Hosseinbor, A Pasha; Chung, Moo K; Wu, Yu-Chien; Fleming, John O; Field, Aaron S; Alexander, Andrew L

2012-01-01

The ensemble average propagator (EAP) describes the 3D average diffusion process of water molecules, capturing both its radial and angular contents, and hence providing rich information about complex tissue microstructure properties. Bessel Fourier orientation reconstruction (BFOR) is one of several analytical, non-Cartesian EAP reconstruction schemes employing multiple shell acquisitions that have recently been proposed. Such modeling bases have not yet been fully exploited in the extraction of rotationally invariant q-space indices that describe the degree of diffusion anisotropy/restrictivity. Such quantitative measures include the zero-displacement probability (P(o)), mean squared displacement (MSD), q-space inverse variance (QIV), and generalized fractional anisotropy (GFA), and all are simply scalar features of the EAP. In this study, a general relationship between MSD and q-space diffusion signal is derived and an EAP-based definition of GFA is introduced. A significant part of the paper is dedicated to utilizing BFOR in a clinical dataset, comprised of 5 multiple sclerosis (MS) patients and 4 healthy controls, to estimate P(o), MSD, QIV, and GFA of corpus callosum, and specifically, to see if such indices can detect changes between normal appearing white matter (NAWM) and healthy white matter (WM). Although the sample size is small, this study is a proof of concept that can be extended to larger sample sizes in the future.

A laboratory study of magnesium-tetrabenz-porphyrin - Lack of agreement with diffuse interstellar bands

NASA Technical Reports Server (NTRS)

Donn, B.; Khanna, R. K.

1980-01-01

The visible and infrared spectra and thermal behavior of the bis-pyridal-magnesium-tetrabenz-porphyrin molecule proposed as the carrier of the diffuse interstellar bands were measured. Of the six band coincidences reported by Johnson (1977), only one, 4430 A, occurs in these experiments. This coincidence requires a special environment, not likely to occur in interstellar space but the infrared spectrum does not support Johnson's vibrational scheme. These spectroscopic and thermal measurements contradict the hypothesis that this molecule causes the diffuse bands.

Transport and Stability of Biological Molecules in Surfactant-Alginate Composite Hydrogels

PubMed Central

Stoppel, Whitney L.; White, Joseph C.; Horava, Sarena D.; Bhatia, Surita R.; Roberts, Susan C.

2013-01-01

Obstructed transport of biological molecules can result in improper release of pharmaceuticals or biologics from biomedical devices. Recent studies have shown that nonionic surfactants, such as Pluronic® F68 (F68), positively alter biomaterial properties, such as mesh size and microcapsule diameter. To further understand the effect of F68 (incorporated at concentrations well above the critical micelle concentration (CMC)) in traditional biomaterials, the transport properties of BSA and riboflavin were investigated in F68-alginate composite hydrogels. Results indicate that small molecule transport (represented by riboflavin) was not significantly hindered by F68 in homogeneously crosslinked hydrogels (up to an 11% decrease in loading capacity and 14% increase in effective diffusion coefficient, Deff), while protein transport in homogeneously crosslinked hydrogels (represented by BSA) was significantly affected (up to a 43% decrease in loading capacity and 40% increase in Deff). For inhomogeneously crosslinked hydrogels (CaCl2 or BaCl2 gelation), the Deff increased up to 50% and 83% for small molecule and proteins, respectively. Variation in the alginate gelation method was shown to affect transport through measurable changes in swelling ratio (30% decrease) and observable changes in crosslinking structure as well as up to a 3.6 and 11.8-fold difference in Deff for riboflavin and BSA, respectively. The change in protein transport properties is a product of mesh size restrictions (10–25 nm estimated by mechanical properties) and BSA-F68 interaction (DLS). Taken as a whole, these results show that incorporation of a nonionic surfactant at concentrations above the CMC can affect device functionality by impeding the transport of large biological molecules. PMID:21798381

Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness.

PubMed Central

Paula, S; Volkov, A G; Van Hoek, A N; Haines, T H; Deamer, D W

1996-01-01

Two mechanisms have been proposed to account for solute permeation of lipid bilayers. Partitioning into the hydrophobic phase of the bilayer, followed by diffusion, is accepted by many for the permeation of water and other small neutral solutes, but transient pores have also been proposed to account for both water and ionic solute permeation. These two mechanisms make distinctively different predictions about the permeability coefficient as a function of bilayer thickness. Whereas the solubility-diffusion mechanism predicts only a modest variation related to bilayer thickness, the pore model predicts an exponential relationship. To test these models, we measured the permeability of phospholipid bilayers to protons, potassium ions, water, urea, and glycerol. Bilayers were prepared as liposomes, and thickness was varied systematically by using unsaturated lipids with chain lengths ranging from 14 to 24 carbon atoms. The permeability coefficient of water and neutral polar solutes displayed a modest dependence on bilayer thickness, with an approximately linear fivefold decrease as the carbon number varied from 14 to 24 atoms. In contrast, the permeability to protons and potassium ions decreased sharply by two orders of magnitude between 14 and 18 carbon atoms, and leveled off, when the chain length was further extended to 24 carbon atoms. The results for water and the neutral permeating solutes are best explained by the solubility-diffusion mechanism. The results for protons and potassium ions in shorter-chain lipids are consistent with the transient pore model, but better fit the theoretical line predicted by the solubility-diffusion model at longer chain lengths. PMID:8770210

Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness

NASA Technical Reports Server (NTRS)

Paula, S.; Volkov, A. G.; Van Hoek, A. N.; Haines, T. H.; Deamer, D. W.

1996-01-01

Two mechanisms have been proposed to account for solute permeation of lipid bilayers. Partitioning into the hydrophobic phase of the bilayer, followed by diffusion, is accepted by many for the permeation of water and other small neutral solutes, but transient pores have also been proposed to account for both water and ionic solute permeation. These two mechanisms make distinctively different predictions about the permeability coefficient as a function of bilayer thickness. Whereas the solubility-diffusion mechanism predicts only a modest variation related to bilayer thickness, the pore model predicts an exponential relationship. To test these models, we measured the permeability of phospholipid bilayers to protons, potassium ions, water, urea, and glycerol. Bilayers were prepared as liposomes, and thickness was varied systematically by using unsaturated lipids with chain lengths ranging from 14 to 24 carbon atoms. The permeability coefficient of water and neutral polar solutes displayed a modest dependence on bilayer thickness, with an approximately linear fivefold decrease as the carbon number varied from 14 to 24 atoms. In contrast, the permeability to protons and potassium ions decreased sharply by two orders of magnitude between 14 and 18 carbon atoms, and leveled off, when the chain length was further extended to 24 carbon atoms. The results for water and the neutral permeating solutes are best explained by the solubility-diffusion mechanism. The results for protons and potassium ions in shorter-chain lipids are consistent with the transient pore model, but better fit the theoretical line predicted by the solubility-diffusion model at longer chain lengths.

Intravital imaging of intestinal lacteals unveils lipid drainage through contractility

PubMed Central

Choe, Kibaek; Jang, Jeon Yeob; Park, Intae; Kim, Yeseul; Ahn, Soyeon; Park, Dae-Young; Hong, Young-Kwon; Alitalo, Kari; Koh, Gou Young; Kim, Pilhan

2015-01-01

Lacteals are lymphatic vessels located at the center of each intestinal villus and provide essential transport routes for lipids and other lipophilic molecules. However, it is unclear how absorbed molecules are transported through the lacteal. Here, we used reporter mice that express GFP under the control of the lymphatic-specific promoter Prox1 and a custom-built confocal microscope and performed intravital real-time visualization of the absorption and transport dynamics of fluorescence-tagged fatty acids (FAs) and various exogenous molecules in the intestinal villi in vivo. These analyses clearly revealed transepithelial absorption of these molecules via enterocytes, diffusive distribution over the lamina propria, and subsequent transport through lacteals. Moreover, we observed active contraction of lacteals, which seemed to be directly involved in dietary lipid drainage. Our analysis revealed that the smooth muscles that surround each lacteal are responsible for contractile dynamics and that lacteal contraction is ultimately controlled by the autonomic nervous system. These results indicate that the lacteal is a unique organ-specific lymphatic system and does not merely serve as a passive conduit but as an active pump that transports lipids. Collectively, using this efficient imaging method, we uncovered drainage of absorbed molecules in small intestinal villus lacteals and the involvement of lacteal contractibility. PMID:26436648

Sugar-influenced water diffusion, interaction, and retention in clay interlayer nanopores probed by theoretical simulations and experimental spectroscopies

NASA Astrophysics Data System (ADS)

Aristilde, Ludmilla; Galdi, Stephen M.; Kelch, Sabrina E.; Aoki, Thalia G.

2017-08-01

Understanding the hydrodynamics in clay nanopores is important for gaining insights into the trapping of water, nutrients, and contaminants in natural and engineered soils. Previous investigations have focused on the interlayer organization and molecular diffusion coefficients (D) of cations and water molecules in cation-saturated interlayer nanopores of smectite clays. Little is known, however, about how these interlayer dynamic properties are influenced by the ubiquitous presence of small organic compounds such as sugars in the soil environment. Here we probed the effects of glucose molecules on montmorillonite interlayer properties. Molecular dynamics simulations revealed re-structuring of the interlayer organization of the adsorptive species. Water-water interactions were disrupted by glucose-water H-bonding interactions. ;Dehydration; of the glucose-populated nanopore led to depletion in the Na solvation shell, which resulted in the accumulation of both Na ions (as inner-sphere complexes) and remaining hydrated water molecules at the mineral surface. This accumulation led to a decrease in both DNa and Dwater. In addition, the reduction in Dglucose as a function of increasing glucose content can be explained by the aggregation of glucose molecules into organic clusters H-bonded to the mineral surface on both walls of the nanopore. Experimental nuclear magnetic resonance and X-ray diffraction data were consistent with the theoretical predictions. Compared to clay interlayers devoid of glucose, increased intensities and new peaks in the 23Na nuclear magnetic resonance spectra confirmed increasing immobilization of Na as a function of increasing glucose content. And, the X-ray diffraction data indicated a reduced collapse of glucose-populated interlayers exposed to decreasing moisture conditions, which led to the maintenance of hydrated clay nanopores. The coupling of theoretical and experimental findings sheds light on the molecular to nanoscale mechanisms that control the enhanced trapping of water molecules and solutes within sugar-enriched clay nanopores.

Mechanisms of the Diffusion of Nonpolar Substances in a Hydrophilic Ionic Liquid

NASA Astrophysics Data System (ADS)

Atamas', N. A.

2018-01-01

The structural-dynamic features of ionic liquid-nonpolar substance systems are studied by means of molecular dynamics using Frenkel's fundamental theory of a liquid and the phonon theory of the thermodynamics of a liquid, in combination with the DL_POLY_4.05 software package. Argon, methane, and benzene molecules serve as the dissolved substances. Model concepts are proposed and analyzed to describe the diffusion of molecules of a dissolved substance in an ionic liquid. It is shown that an increase in the mass of the molecules of a dissolved nonpolar substance correlates with their mobility in a hydrophilic ionic liquid (IL). This determines the diffusion of the components of dmim+/Cl- IL solutions and is responsible for the anomalous behavior of the solubility of nonpolar substances in them.

Anomalous extracellular diffusion in rat cerebellum.

PubMed

Xiao, Fanrong; Hrabe, Jan; Hrabetova, Sabina

2015-05-05

Extracellular space (ECS) is a major channel transporting biologically active molecules and drugs in the brain. Diffusion-mediated transport of these substances is hindered by the ECS structure but the microscopic basis of this hindrance is not fully understood. One hypothesis proposes that the hindrance originates in large part from the presence of dead-space (DS) microdomains that can transiently retain diffusing molecules. Because previous theoretical and modeling work reported an initial period of anomalous diffusion in similar environments, we expected that brain regions densely populated by DS microdomains would exhibit anomalous extracellular diffusion. Specifically, we targeted granular layers (GL) of rat and turtle cerebella that are populated with large and geometrically complex glomeruli. The integrative optical imaging (IOI) method was employed to evaluate diffusion of fluorophore-labeled dextran (MW 3000) in GL, and the IOI data analysis was adapted to quantify the anomalous diffusion exponent dw from the IOI records. Diffusion was significantly anomalous in rat GL, where dw reached 4.8. In the geometrically simpler turtle GL, dw was elevated but not robustly anomalous (dw = 2.6). The experimental work was complemented by numerical Monte Carlo simulations of anomalous ECS diffusion in several three-dimensional tissue models containing glomeruli-like structures. It demonstrated that both the duration of transiently anomalous diffusion and the anomalous exponent depend on the size of model glomeruli and the degree of their wrapping. In conclusion, we have found anomalous extracellular diffusion in the GL of rat cerebellum. This finding lends support to the DS microdomain hypothesis. Transiently anomalous diffusion also has a profound effect on the spatiotemporal distribution of molecules released into the ECS, especially at diffusion distances on the order of a few cell diameters, speeding up short-range diffusion-mediated signals in less permeable structures. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

First Principles Study for Proton Transport and Diffusion Behavior in Hydrous Hexagonal WO3

NASA Astrophysics Data System (ADS)

Liu, Chi-Ping; Zhou, Fei; Ozolins, Vidvuds; QPAM Team

2013-03-01

Proton transport is of great importance in biological species and energy storage and conversion systems. Previous studies have shown fast proton conduction in liquids and polymers but seldom in inorganic materials. In this work, first principles density functional theory (DFT) reveals that the formation of hydronium and water chains inside the hexagonal channels plays the key roles for the anomalously fast proton transport, by following modified Grotthuss mechanism. Our DFT study shows the detailed microscopic proton diffusion mechanism along the channel in hydrous WO3 with 50% water composition, which is proper for water chain formation. The water chain in the channel serves as a possible diffusion media for hydronium (H3O +) . With the continuous formation and cleavage of hydrogen bonds in the channel, the hydronium diffuses by hydrogen bonds exchange between water molecules. This mechanism is very similar with Grotthuss relay mechanism for proton transport in liquid. The possible proton diffusion were studied for hydronium is either far away from the water chain bond defect or next to H2O defect at the end of water chain. The diffusion barriers for both conditions are around 150 meV to 200 meV, and water defects reorganization in the chain is the rate-limited step for proton diffusion. These small diffusion barriers could explain the fast 1-D proton transport in hydrous WO3 channel. Further studies about fast proton transport in other inorganic materials could be an important topic in not only biochemistry but also clean energy applications like fuel cell applications.

Dynamic interactions between a membrane binding protein and lipids induce fluctuating diffusivity

PubMed Central

Yamamoto, Eiji; Akimoto, Takuma; Kalli, Antreas C.; Yasuoka, Kenji; Sansom, Mark S. P.

2017-01-01

Pleckstrin homology (PH) domains are membrane-binding lipid recognition proteins that interact with phosphatidylinositol phosphate (PIP) molecules in eukaryotic cell membranes. Diffusion of PH domains plays a critical role in biological reactions on membrane surfaces. Although diffusivity can be estimated by long-time measurements, it lacks information on the short-time diffusive nature. We reveal two diffusive properties of a PH domain bound to the surface of a PIP-containing membrane using molecular dynamics simulations. One is fractional Brownian motion, attributed to the motion of the lipids with which the PH domain interacts. The other is temporally fluctuating diffusivity; that is, the short-time diffusivity of the bound protein changes substantially with time. Moreover, the diffusivity for short-time measurements is intrinsically different from that for long-time measurements. This fluctuating diffusivity results from dynamic changes in interactions between the PH domain and PIP molecules. Our results provide evidence that the complexity of protein-lipid interactions plays a crucial role in the diffusion of proteins on biological membrane surfaces. Changes in the diffusivity of PH domains and related membrane-bound proteins may in turn contribute to the formation/dissolution of protein complexes in membranes. PMID:28116358

Optimizing home dialysis: role of hemodiafiltration.

PubMed

Vilar, Enric; Farrington, Ken; Bates, Chris; Mumford, Carol; Greenwood, Roger

2011-01-01

Over the last 40 years the technical obstacles which prevented a convective contribution to diffusive dialysis have been overcome. Hemodiafiltration represents a natural evolution of intermittent extracorporeal blood purification and the technology is now available to offer this as standard treatment in-center. The first randomized control trial of dialysis dose (National Cooperative Dialysis Study) showed that for three times weekly dialysis a critical level of urea clearance was necessary to ensure complication-free survival, the effect being noticeable by 3 months. Following this, observational studies suggested that higher doses improved longer term outcome. In a second large randomized controlled study (HEMO), higher small molecule clearance did not further improve outcome, but high-flux membranes, which permitted enhanced clearance of middle molecules, appeared to confer survival benefit in patients who had already been on dialysis > 3.7 years. Recently, outcomes from the Membrane Permeability Outcome study confirmed a survival benefit of high-flux membranes in high-risk patients. These studies indicate that in the medium term survival is critically dependent on achieving a minimum level of small solute removal. However, longer term survival (measured in years or decades) not only requires better small solute clearance but also enhanced clearance of middle molecules, the toxicity of which manifest over longer time scales. The rationale for convective treatment is strongest, therefore in those patients who have the greatest potential for long-term survival. Patients who opt for self-care at home to allow frequent dialysis generally are constituents of this group. Hemodiafiltration is likely to become standard therapy in-center and in the home. Copyright © 2011 S. Karger AG, Basel.

Ultrasmall visible-to-near-infrared emitting silver-sulfide quantum dots for cancer detection and imaging

NASA Astrophysics Data System (ADS)

Tang, Rui; Xu, Baogang; Shen, Duanwen; Sudlow, Gail; Achilefu, Samuel

2018-02-01

The large size of many near infrared (NIR) fluorescent nanoparticles prevents rapid extravasation from blood vessels and subsequent diffusion to tumors. This confines in vivo uptake to the peritumoral space and results in high liver retention. We developed a viscosity modulated approach to synthesize ultrasmall silver sulfide quantum dots (QDs) with distinct tunable light emission from visible to near-infrared in spectrum and a QD core diameter between less than 5 nm. Further functionalization of these Ag2S QDs with different type of molecules such as targeting peptides, retains monodisperse, relatively small water soluble QDs without loss of the functionality of the peptide's high binding affinity to cancerous tumor. Fluorescence and electron microscopy showed that selective integrin-mediated internalization was observed only in cancer cells treated with the peptide-labeled QDs, demonstrating that the unlabeled hydrophilic nanoparticles exhibit characteristics of negatively charged fluorescent dye molecules, which typically do not internalize in cells. The biodistribution profiles of intravenously administered QDs in different mouse models of cancer reveal an exceptionally high tumor-to-liver uptake ratio, suggesting that the small sized QDs evaded conventional opsonization and subsequent high uptake in the liver and spleen. The seamless tunability of the QDs over a wide spectral range with only a small increase in size, as well as the ease of labeling the bright and non-cytotoxic QDs with biomolecules, provides a platform for multiplexing information, tracking the trafficking of single molecules in cells, and selectively targeting disease biomarkers in living organisms without premature QD opsonization in circulating blood.

A small molecule norspermidine in combination with silver ion enhances dispersal and disinfection of multi-species wastewater biofilms.

PubMed

Wu, Yachuan; Quan, Xiangchun; Si, Xiurong; Wang, Xinrui

2016-06-01

Detrimental biofilms have become a great concern in many areas due to their strong resistance and insensitivity to traditional antimicrobial agents. Norspermidine is a potent small molecule for biofilm dispersal. In this study, silver ion, a conventional inorganic biocide, was combined with norspermidine and used for control and removal of multi-species biofilms formed by a mixed culture from wastewater treatment systems. Results showed that silver ion (0.01-1 mg/L) treatment alone failed to remove the existing wastewater biofilms. Norspermidine at the concentrations of 500-1000 μM was capable to disrupt and disperse the existing biofilms with a biofilm reduction of 21-34 % after 24-h exposure. The combined treatment with norspermidine (500 μM) and silver ion (0.01 mg/L) increased biofilm reduction to 48 % (24-h exposure). The combined treatment also enhanced biofilm disinfection ratio (82 %, 2-h exposure) by 2.0- and 2.6-folds compared to norspermidine (27 %) or silver ion (23 %) treatment alone, respectively. Confocal laser scanning microscopic (CLSM) observations found that norspermidine could disrupt biofilm matrix and promote biofilm dispersal via breaking down exopolysaccharides. The combined treatment increased the reduction in biofilm cell density and viability, possibly due to the damage of biofilm matrix, enhanced silver ion diffusion in biofilms, and increased biofilm sensitivity. These findings indicate that the combination of a small molecule norspermidine with a traditional biocide silver ion presents a novel strategy to remove and kill biofilms, which have a potential application in addressing wastewater biofilm-related issues.

Phase transformations of 4,4'-biphenyldicarboxylic acid on Cu(001)

NASA Astrophysics Data System (ADS)

Schwarz, Daniel; van Gastel, Raoul; Zandvliet, Harold J. W.; Poelsema, Bene

2012-06-01

The growth and structure of 4,4'-biphenyldicarboxylic-acid (BDA) on Cu(001) at temperatures between 300 and 400 K was studied by low energy electron microscopy and μ-LEED. First, the adsorbed BDA molecules form a disordered dilute phase. Once this phase reaches a sufficiently high density, a crystalline phase nucleates, in which the molecules form a hydrogen-bonded two-dimensional (2D) supramolecular c(8×8) network. By a careful analysis of the bright-field image intensity, we can measure the density in the dilute phase, which is up to 30% of that in the crystalline phase. From the respective equilibrium densities at different temperatures, we determine the 2D phase diagram and extract a cohesive energy of 0.35 eV. We also analyze the island decay behavior and estimate the BDA molecule diffusion constants. Steps are found to be highly transparent for diffusing BDA molecules. In the temperature range of 362-400 K, we find chemical diffusion constants between 850-1700nm2s-1.

Separation of gases by diffusion

DOEpatents

Peieris, R. E.; Simon, F. E.; Arms, H. S.

1960-12-13

An apparatus is described for the separation of mixtures of gaseous or vaporous media by diffusion through a permeable membrane. The apparatus consists principally of a housing member having an elongated internal chamber dissected longitudinally by a permeable membrane. Means are provided for producing a pressure difference between opposite sides of the membrane to cause a flow of the media in the chamber therethrough. This pressure difference is alternated between opposite sides of the membrane to produce an oscillating flow through the membrane. Additional means is provided for producing flow parallel to the membrane in opposite directions on the two sides thereof and of the same frequency and in phase wlth the alternating pressure difference. The lighter molecules diffuse through the membrane more readily than the heavier molecules and the parallel flow effects a net transport of the lighter molecules in one direction and the heavier molecules in the opposite direction wlthin the chamber. By these means a concentration gradient along the chamber is established. (auth)

High-Performance Simulations of the Diffusion Characteristics of a Pentacene Derivative on Gold Surfaces

NASA Astrophysics Data System (ADS)

Miller, Ryan; Larson, Amanda; Pohl, Karsten

Pentacene serves as a backbone for several molecules that provide attractive qualities for organic photovoltaic devices. One of these pentacene derivatives is 5 6,7-trithiapentacene-13-one (TTPO), which is unique in that it achieves its lowest energy configuration on Au(1 1 1) surfaces with the thiol group angled down towards the surface, allowing many molecules to pack closely together and form molecular nanowires. However, TTPO diffuses on flat surfaces, making it difficult for the self-assembly process to be initiated. With the help of the low-energy sites in surface defects and Au(7 8 8) step edges, TTPO molecules can be anchored in place on surfaces, allowing for chain formation to begin. By using high-performance Density Functional Theory based molecular dynamics calculations, the molecules can be shown to stay localized to these bonding sites and serve as a basis for chain formation. In addition, by simulating various temperatures with a Nose-Hoover thermostat, we can analyze how temperature affects anchoring ability and diffusion properties.

Molecular dynamics simulation of three plastic additives' diffusion in polyethylene terephthalate.

PubMed

Li, Bo; Wang, Zhi-Wei; Lin, Qin-Bao; Hu, Chang-Ying

2017-06-01

Accurate diffusion coefficient data of additives in a polymer are of paramount importance for estimating the migration of the additives over time. This paper shows how this diffusion coefficient can be estimated for three plastic additives [2-(2'-hydroxy-5'-methylphenyl) (UV-P), 2,6-di-tert-butyl-4-methylphenol (BHT) and di-(2-ethylhexyl) phthalate (DEHP)] in polyethylene terephthalate (PET) using the molecular dynamics (MD) simulation method. MD simulations were performed at temperatures of 293-433 K. The diffusion coefficient was calculated through the Einstein relationship connecting the data of mean-square displacement at different times. Comparison of the diffusion coefficients simulated by the MD simulation technique, predicted by the Piringer model and experiments, showed that, except for a few samples, the MD-simulated values were in agreement with the experimental values within one order of magnitude. Furthermore, the diffusion process for additives is discussed in detail, and four factors - the interaction energy between additive molecules and PET, fractional free volume, molecular shape and size, and self-diffusion of the polymer - are proposed to illustrate the microscopic diffusion mechanism. The movement trajectories of additives in PET cell models suggested that the additive molecules oscillate slowly rather than hopping for a long time. Occasionally, when a sufficiently large hole was created adjacently, the molecule could undergo spatial motion by jumping into the free-volume hole and consequently start a continuous oscillation and hop. The results indicate that MD simulation is a useful approach for predicting the microstructure and diffusion coefficient of plastic additives, and help to estimate the migration level of additives from PET packaging.

Gel integration for microfluidic applications.

PubMed

Zhang, Xuanqi; Li, Lingjun; Luo, Chunxiong

2016-05-21

Molecular diffusive membranes or materials are important for biological applications in microfluidic systems. Hydrogels are typical materials that offer several advantages, such as free diffusion for small molecules, biocompatibility with most cells, temperature sensitivity, relatively low cost, and ease of production. With the development of microfluidic applications, hydrogels can be integrated into microfluidic systems by soft lithography, flow-solid processes or UV cure methods. Due to their special properties, hydrogels are widely used as fluid control modules, biochemical reaction modules or biological application modules in different applications. Although hydrogels have been used in microfluidic systems for more than ten years, many hydrogels' properties and integrated techniques have not been carefully elaborated. Here, we systematically review the physical properties of hydrogels, general methods for gel-microfluidics integration and applications of this field. Advanced topics and the outlook of hydrogel fabrication and applications are also discussed. We hope this review can help researchers choose suitable methods for their applications using hydrogels.

Communication: Modeling of concentration dependent water diffusivity in ionic solutions: Role of intermolecular charge transfer

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

Yao, Yi; Berkowitz, Max L., E-mail: maxb@unc.edu, E-mail: ykanai@unc.edu; Kanai, Yosuke, E-mail: maxb@unc.edu, E-mail: ykanai@unc.edu

2015-12-28

The translational diffusivity of water in solutions of alkali halide salts depends on the identity of ions, exhibiting dramatically different behavior even in solutions of similar salts of NaCl and KCl. The water diffusion coefficient decreases as the salt concentration increases in NaCl. Yet, in KCl solution, it slightly increases and remains above bulk value as salt concentration increases. Previous classical molecular dynamics simulations have failed to describe this important behavior even when polarizable models were used. Here, we show that inclusion of dynamical charge transfer among water molecules produces results in a quantitative agreement with experiments. Our results indicatemore » that the concentration-dependent diffusivity reflects the importance of many-body effects among the water molecules in aqueous ionic solutions. Comparison with quantum mechanical calculations shows that a heterogeneous and extended distribution of charges on water molecules around the ions due to ion-water and also water-water charge transfer plays a very important role in controlling water diffusivity. Explicit inclusion of the charge transfer allows us to model accurately the difference in the concentration-dependent water diffusivity between Na{sup +} and K{sup +} ions in simulations, and it is likely to impact modeling of a wide range of systems for medical and technological applications.« less

Clogging in micromachined Joule-Thomson coolers: Mechanism and preventive measures

NASA Astrophysics Data System (ADS)

Cao, H. S.; Vanapalli, S.; Holland, H. J.; Vermeer, C. H.; ter Brake, H. J. M.

2013-07-01

Micromachined Joule-Thomson coolers can be used for cooling small electronic devices. However, a critical issue for long-term operation of these microcoolers is the clogging caused by the deposition of water that is present as impurity in the working fluid. We present a model that describes the deposition process considering diffusion and kinetics of water molecules. In addition, the deposition and sublimation process was imaged, and the experimental observation fits well to the modeling predictions. By changing the temperature profile along the microcooler, the operating time of the microcooler under test at 105 K extends from 11 to 52 h.

Mobility measurement by analysis of fluorescence photobleaching recovery kinetics.

PubMed Central

Axelrod, D; Koppel, D E; Schlessinger, J; Elson, E; Webb, W W

1976-01-01

Fluorescence photobleaching recovery (FPR) denotes a method for measuring two-dimensional lateral mobility of fluorescent particles, for example, the motion of fluorescently labeled molecules in approximately 10 mum2 regions of a single cell surface. A small spot on the fluorescent surface is photobleached by a brief exposure to an intense focused laser beam, and the subsequent recovery of the fluorescence is monitored by the same, but attenuated, laser beam. Recovery occurs by replenishment of intact fluorophore in the bleached spot by lateral transport from the surrounding surface. We present the theoretical basis and some practical guidelines for simple, rigorous analysis of FPR experiments. Information obtainable from FPR experiments includes: (a) identification of transport process type, i.e. the admixture of random diffusion and uniform directed flow; (b) determination of the absolute mobility coefficient, i.e. the diffusion constant and/or flow velocity; and (c) the fraction of total fluorophore which is mobile. To illustrate the experimental method and to verify the theory for diffusion, we describe some model experiments on aqueous solutions of rhodamine 6G. PMID:786399

Functional Implications of Photosystem II Crystal Formation in Photosynthetic Membranes*

PubMed Central

Tietz, Stefanie; Puthiyaveetil, Sujith; Enlow, Heather M.; Yarbrough, Robert; Wood, Magnus; Semchonok, Dmitry A.; Lowry, Troy; Li, Zhirong; Jahns, Peter; Boekema, Egbert J.; Lenhert, Steven; Niyogi, Krishna K.; Kirchhoff, Helmut

2015-01-01

The structural organization of proteins in biological membranes can affect their function. Photosynthetic thylakoid membranes in chloroplasts have the remarkable ability to change their supramolecular organization between disordered and semicrystalline states. Although the change to the semicrystalline state is known to be triggered by abiotic factors, the functional significance of this protein organization has not yet been understood. Taking advantage of an Arabidopsis thaliana fatty acid desaturase mutant (fad5) that constitutively forms semicrystalline arrays, we systematically test the functional implications of protein crystals in photosynthetic membranes. Here, we show that the change into an ordered state facilitates molecular diffusion of photosynthetic components in crowded thylakoid membranes. The increased mobility of small lipophilic molecules like plastoquinone and xanthophylls has implications for diffusion-dependent electron transport and photoprotective energy-dependent quenching. The mobility of the large photosystem II supercomplexes, however, is impaired, leading to retarded repair of damaged proteins. Our results demonstrate that supramolecular changes into more ordered states have differing impacts on photosynthesis that favor either diffusion-dependent electron transport and photoprotection or protein repair processes, thus fine-tuning the photosynthetic energy conversion. PMID:25897076

Extracellular Sheets and Tunnels Modulate Glutamate Diffusion in Hippocampal Neuropil

PubMed Central

Kinney, Justin P.; Spacek, Josef; Bartol, Thomas M.; Bajaj, Chandrajit L.; Harris, Kristen M.; Sejnowski, Terrence J.

2012-01-01

Although the extracellular space in the neuropil of the brain is an important channel for volume communication between cells and has other important functions, its morphology on the micron scale has not been analyzed quantitatively owing to experimental limitations. We used manual and computational techniques to reconstruct the 3D geometry of 180 μm3 of rat CA1 hippocampal neuropil from serial electron microscopy and corrected for tissue shrinkage to reflect the in vivo state. The reconstruction revealed an interconnected network of 40–80 nm diameter tunnels, formed at the junction of three or more cellular processes, spanned by sheets between pairs of cell surfaces with 10–40 nm width. The tunnels tended to occur around synapses and axons, and the sheets were enriched around astrocytes. Monte Carlo simulations of diffusion within the reconstructed neuropil demonstrate that the rate of diffusion of neurotransmitter and other small molecules was slower in sheets than in tunnels. Thus, the non-uniformity found in the extracellular space may have specialized functions for signaling (sheets) and volume transmission (tunnels). PMID:22740128

Principle of Parsimony, Fake Science, and Scales

NASA Astrophysics Data System (ADS)

Yeh, T. C. J.; Wan, L.; Wang, X. S.

2017-12-01

Considering difficulties in predicting exact motions of water molecules, and the scale of our interests (bulk behaviors of many molecules), Fick's law (diffusion concept) has been created to predict solute diffusion process in space and time. G.I. Taylor (1921) demonstrated that random motion of the molecules reach the Fickian regime in less a second if our sampling scale is large enough to reach ergodic condition. Fick's law is widely accepted for describing molecular diffusion as such. This fits the definition of the parsimony principle at the scale of our concern. Similarly, advection-dispersion or convection-dispersion equation (ADE or CDE) has been found quite satisfactory for analysis of concentration breakthroughs of solute transport in uniformly packed soil columns. This is attributed to the solute is often released over the entire cross-section of the column, which has sampled many pore-scale heterogeneities and met the ergodicity assumption. Further, the uniformly packed column contains a large number of stationary pore-size heterogeneity. The solute thus reaches the Fickian regime after traveling a short distance along the column. Moreover, breakthrough curves are concentrations integrated over the column cross-section (the scale of our interest), and they meet the ergodicity assumption embedded in the ADE and CDE. To the contrary, scales of heterogeneity in most groundwater pollution problems evolve as contaminants travel. They are much larger than the scale of our observations and our interests so that the ergodic and the Fickian conditions are difficult. Upscaling the Fick's law for solution dispersion, and deriving universal rules of the dispersion to the field- or basin-scale pollution migrations are merely misuse of the parsimony principle and lead to a fake science ( i.e., the development of theories for predicting processes that can not be observed.) The appropriate principle of parsimony for these situations dictates mapping of large-scale heterogeneities as detailed as possible and adapting the Fick's law for effects of small-scale heterogeneity resulting from our inability to characterize them in detail.

Physics, Techniques and Review of Neuroradiological Applications of Diffusion Kurtosis Imaging (DKI).

PubMed

Marrale, M; Collura, G; Brai, M; Toschi, N; Midiri, F; La Tona, G; Lo Casto, A; Gagliardo, C

2016-12-01

In recent years many papers about diagnostic applications of diffusion tensor imaging (DTI) have been published. This is because DTI allows to evaluate in vivo and in a non-invasive way the process of diffusion of water molecules in biological tissues. However, the simplified description of the diffusion process assumed in DTI does not permit to completely map the complex underlying cellular components and structures, which hinder and restrict the diffusion of water molecules. These limitations can be partially overcome by means of diffusion kurtosis imaging (DKI). The aim of this paper is the description of the theory of DKI, a new topic of growing interest in radiology. DKI is a higher order diffusion model that is a straightforward extension of the DTI model. Here, we analyze the physics underlying this method, we report our MRI acquisition protocol with the preprocessing pipeline used and the DKI parametric maps obtained on a 1.5 T scanner, and we review the most relevant clinical applications of this technique in various neurological diseases.

Effects of added surfactant on swelling and molecular transport in drug-loaded tablets based on hydrophobically modified poly(acrylic acid).

PubMed

Knöös, Patrik; Wahlgren, Marie; Topgaard, Daniel; Ulvenlund, Stefan; Piculell, Lennart

2014-08-14

A combination of NMR chemical shift imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when tablets of hydrophobically modified poly(acrylic acid) loaded with a drug (griseofulvin) swell in water in the presence or absence of surfactant (sodium octylbenzenesulfonate). The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective surfactant transport that occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Because of the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outward as the matrix swells. The added surfactant has little effect on the transport of drug because both undissolved solid drug and surfactant-solubilized drug function as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix.

The formation of molecules in interstellar clouds from singly and multiply ionized atoms

NASA Technical Reports Server (NTRS)

Langer, W. D.

1978-01-01

The suggestion is considered that multiply ionized atoms produced by K- and L-shell X-ray ionization and cosmic-ray ionization can undergo ion-molecule reactions and also initiate molecule production. The role of X-rays in molecule production in general is discussed, and the contribution to molecule production of the C(+) radiative association with hydrogen is examined. Such gas-phase reactions of singly and multiply ionized atoms are used to calculate molecular abundances of carbon-, nitrogen-, and oxygen-bearing species. The column densities of the molecules are evaluated on the basis of a modified version of previously developed isobaric cloud models. It is found that reactions of multiply ionized carbon with H2 can contribute a significant fraction of the observed CH in diffuse interstellar clouds in the presence of diffuse X-ray structures or discrete X-ray sources and that substantial amounts of CH(+) can be produced under certain conditions.

Analysis of Decomposition for Structure I Methane Hydrate by Molecular Dynamics Simulation

NASA Astrophysics Data System (ADS)

Wei, Na; Sun, Wan-Tong; Meng, Ying-Feng; Liu, An-Qi; Zhou, Shou-Wei; Guo, Ping; Fu, Qiang; Lv, Xin

2018-05-01

Under multi-nodes of temperatures and pressures, microscopic decomposition mechanisms of structure I methane hydrate in contact with bulk water molecules have been studied through LAMMPS software by molecular dynamics simulation. Simulation system consists of 482 methane molecules in hydrate and 3027 randomly distributed bulk water molecules. Through analyses of simulation results, decomposition number of hydrate cages, density of methane molecules, radial distribution function for oxygen atoms, mean square displacement and coefficient of diffusion of methane molecules have been studied. A significant result shows that structure I methane hydrate decomposes from hydrate-bulk water interface to hydrate interior. As temperature rises and pressure drops, the stabilization of hydrate will weaken, decomposition extent will go deep, and mean square displacement and coefficient of diffusion of methane molecules will increase. The studies can provide important meanings for the microscopic decomposition mechanisms analyses of methane hydrate.

Monoclonal Antibody Therapy and Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2013-01-08

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Waldenström Macroglobulinemia

Physics of Molecules

NASA Astrophysics Data System (ADS)

Williams, D.; Murdin, P.

2000-11-01

Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

Generation and precise control of dynamic biochemical gradients for cellular assays

NASA Astrophysics Data System (ADS)

Saka, Yasushi; MacPherson, Murray; Giuraniuc, Claudiu V.

2017-03-01

Spatial gradients of diffusible signalling molecules play crucial roles in controlling diverse cellular behaviour such as cell differentiation, tissue patterning and chemotaxis. In this paper, we report the design and testing of a microfluidic device for diffusion-based gradient generation for cellular assays. A unique channel design of the device eliminates cross-flow between the source and sink channels, thereby stabilizing gradients by passive diffusion. The platform also enables quick and flexible control of chemical concentration that makes highly dynamic gradients in diffusion chambers. A model with the first approximation of diffusion and surface adsorption of molecules recapitulates the experimentally observed gradients. Budding yeast cells cultured in a gradient of a chemical inducer expressed a reporter fluorescence protein in a concentration-dependent manner. This microfluidic platform serves as a versatile prototype applicable to a broad range of biomedical investigations.

Single-Molecule View of Small RNA-Guided Target Search and Recognition.

PubMed

Globyte, Viktorija; Kim, Sung Hyun; Joo, Chirlmin

2018-05-20

Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems. We discuss different steps involved in search and recognition, from the initial complex prearrangement into the target-search competent state to the final proofreading steps. We focus on target search mechanisms that range from weak interactions, to one- and three-dimensional diffusion, to conformational proofreading. We compare the mechanisms of Argonaute and CRISPR with a well-studied target search system, RecA.

An artificial molecular pump

NASA Astrophysics Data System (ADS)

Cheng, Chuyang; McGonigal, Paul R.; Schneebeli, Severin T.; Li, Hao; Vermeulen, Nicolaas A.; Ke, Chenfeng; Stoddart, J. Fraser

2015-06-01

Carrier proteins consume fuel in order to pump ions or molecules across cell membranes, creating concentration gradients. Their control over diffusion pathways, effected entirely through noncovalent bonding interactions, has inspired chemists to devise artificial systems that mimic their function. Here, we report a wholly artificial compound that acts on small molecules to create a gradient in their local concentration. It does so by using redox energy and precisely organized noncovalent bonding interactions to pump positively charged rings from solution and ensnare them around an oligomethylene chain, as part of a kinetically trapped entanglement. A redox-active viologen unit at the heart of a dumbbell-shaped molecular pump plays a dual role, first attracting and then repelling the rings during redox cycling, thereby enacting a flashing energy ratchet mechanism with a minimalistic design. Our artificial molecular pump performs work repetitively for two cycles of operation and drives rings away from equilibrium toward a higher local concentration.

Ultrafast Diffusion of a Fluorescent Cholesterol Analog in Compartmentalized Plasma Membranes

PubMed Central

Hiramoto-Yamaki, Nao; Tanaka, Kenji A K; Suzuki, Kenichi G N; Hirosawa, Koichiro M; Miyahara, Manami S H; Kalay, Ziya; Tanaka, Koichiro; Kasai, Rinshi S; Kusumi, Akihiro; Fujiwara, Takahiro K

2014-01-01

Cholesterol distribution and dynamics in the plasma membrane (PM) are poorly understood. The recent development of Bodipy488-conjugated cholesterol molecule (Bdp-Chol) allowed us to study cholesterol behavior in the PM, using single fluorescent-molecule imaging. Surprisingly, in the intact PM, Bdp-Chol diffused at the fastest rate ever found for any molecules in the PM, with a median diffusion coefficient (D) of 3.4 µm2/second, which was ∼10 times greater than that of non-raft phospholipid molecules (0.33 µm2/second), despite Bdp-Chol's probable association with raft domains. Furthermore, Bdp-Chol exhibited no sign of entrapment in time scales longer than 0.5 milliseconds. In the blebbed PM, where actin filaments were largely depleted, Bdp-Chol and Cy3-conjugated dioleoylphosphatidylethanolamine (Cy3-DOPE) diffused at comparable Ds (medians = 5.8 and 6.2 µm2/second, respectively), indicating that the actin-based membrane skeleton reduces the D of Bdp-Chol only by a factor of ∼2 from that in the blebbed PM, whereas it reduces the D of Cy3-DOPE by a factor of ∼20. These results are consistent with the previously proposed model, in which the PM is compartmentalized by the actin-based membrane-skeleton fence and its associated transmembrane picket proteins for the macroscopic diffusion of all of the membrane molecules, and suggest that the probability of Bdp-Chol passing through the compartment boundaries, once it enters the boundary, is ∼10× greater than that of Cy3-DOPE. Since the compartment sizes are greater than those of the putative raft domains, we conclude that raft domains coexist with membrane-skeleton-induced compartments and are contained within them. PMID:24506328

Evolutionary dynamics of enzymes.

PubMed

Demetrius, L

1995-08-01

This paper codifies and rationalizes the large diversity in reaction rates and substrate specificity of enzymes in terms of a model which postulates that the kinetic properties of present-day enzymes are the consequence of the evolutionary force of mutation and selection acting on a class of primordial enzymes with poor catalytic activity and broad substrate specificity. Enzymes are classified in terms of their thermodynamic parameters, activation enthalpy delta H* and activation entropy delta S*, in their kinetically significant transition states as follows: type 1, delta H* > 0, delta S* < 0; type 2, delta H* < or = 0, delta S* < or = 0; type 3, delta H* > 0, delta S* > 0. We study the evolutionary dynamics of these three classes of enzymes subject to mutation, which acts at the level of the gene which codes for the enzyme and selection, which acts on the organism that contains the enzyme. Our model predicts the following evolutionary trends in the reaction rate and binding specificity for the three classes of molecules. In type 1 enzymes, evolution results in random, non-directional changes in the reaction rate and binding specificity. In type 2 and 3 enzymes, evolution results in a unidirectional increase in both the reaction rate and binding specificity. We exploit these results in order to codify the diversity in functional properties of present-day enzymes. Type 1 molecules will be described by intermediate reaction rates and broad substrate specificity. Type 2 enzymes will be characterized by diffusion-controlled rates and absolute substrate specificity. The type 3 catalysts can be further subdivided in terms of their activation enthalpy into two classes: type 3a (delta H* small) and type 3b (delta H* large). We show that type 3a will be represented by the same functional properties that identify type 2, namely, diffusion-controlled rates and absolute substrate specificity, whereas type 3b will be characterized by non-diffusion-controlled rates and absolute substrate specificity. We infer from this depiction of the three classes of enzymes, a general relation between the two functional properties, reaction rate and substrate specificity, namely, enzymes with diffusion-controlled rates have absolute substrate specificity. By appealing to energetic considerations, we furthermore show that enzymes with diffusion-controlled rates (types 2 and 3a) form a small subset of the class of all enzymes. This codification of present-day enzymes derived from an evolutionary model, essentially relates the structural properties of enzymes, as described by their thermodynamic parameters, to their functional properties, as represented by the reaction rate and substrate specificity.

Separation of Anisotropy and Exchange Broadening Using 15N CSA- 15N- 1H Dipole-Dipole Relaxation Cross-Correlation Experiments

NASA Astrophysics Data System (ADS)

Renner, Christian; Holak, Tad A.

2000-08-01

Based on the measurement of cross-correlation rates between 15N CSA and 15N-1H dipole-dipole relaxation we propose a procedure for separating exchange contributions to transverse relaxation rates (R2 = 1/T2) from effects caused by anisotropic rotational diffusion of the protein molecule. This approach determines the influence of anisotropy and chemical exchange processes independently and therefore circumvents difficulties associated with the currently standard use of T1/T2 ratios to determine the rotational diffusion tensor. We find from computer simulations that, in the presence of even small amounts of internal flexibility, fitting T1/T2 ratios tends to underestimate the anisotropy of overall tumbling. An additional problem exists when the N-H bond vector directions are not distributed homogeneously over the surface of a unit sphere, such as in helix bundles or β-sheets. Such a case was found in segment 4 of the gelation factor (ABP 120), an F-actin cross-linking protein, in which the diffusion tensor cannot be calculated from T1/T2 ratios. The 15N CSA tensor of the residues for this β-sheet protein was found to vary even within secondary structure elements. The use of a common value for the whole protein molecule therefore might be an oversimplification. Using our approach it is immediately apparent that no exchange broadening exists for segment 4 although strongly reduced T2 relaxation times for several residues could be mistaken as indications for exchange processes.

Quorum Sensing Signaling Molecules Produced by Reference and Emerging Soft-Rot Bacteria (Dickeya and Pectobacterium spp.)

PubMed Central

Crépin, Alexandre; Barbey, Corinne; Beury-Cirou, Amélie; Hélias, Valérie; Taupin, Laure; Reverchon, Sylvie; Nasser, William; Faure, Denis; Dufour, Alain; Orange, Nicole; Feuilloley, Marc; Heurlier, Karin; Burini, Jean-François; Latour, Xavier

2012-01-01

Background Several small diffusible molecules are involved in bacterial quorum sensing and virulence. The production of autoinducers-1 and -2, quinolone, indole and γ-amino butyrate signaling molecules was investigated in a set of soft-rot bacteria belonging to six Dickeya or Pectobacterium species including recent or emerging potato isolates. Methodology/Principal Findings Using bacterial biosensors, immunoassay, and chromatographic analysis, we showed that soft-rot bacteria have the common ability to produce transiently during their exponential phase of growth the N-3-oxo-hexanoyl- or the N-3-oxo-octanoyl-l-homoserine lactones and a molecule of the autoinducer-2 family. Dickeya spp. produced in addition the indole-3-acetic acid in tryptophan-rich conditions. All these signaling molecules have been identified for the first time in the novel Dickeya solani species. In contrast, quinolone and γ-amino butyrate signals were not identified and the corresponding synthases are not present in the available genomes of soft-rot bacteria. To determine if the variations of signal production according to growth phase could result from expression modifications of the corresponding synthase gene, the respective mRNA levels were estimated by reverse transcriptase-PCR. While the N-acyl-homoserine lactone production is systematically correlated to the synthase expression, that of the autoinducer-2 follows the expression of an enzyme upstream in the activated methyl cycle and providing its precursor, rather than the expression of its own synthase. Conclusions/Significance Despite sharing the S-adenosylmethionine precursor, no strong link was detected between the production kinetics or metabolic pathways of autoinducers-1 and -2. In contrast, the signaling pathway of autoinducer-2 seems to be switched off by the indole-3-acetic acid pathway under tryptophan control. It therefore appears that the two genera of soft-rot bacteria have similarities but also differences in the mechanisms of communication via the diffusible molecules. Our results designate autoinducer-1 lactones as the main targets for a global biocontrol of soft-rot bacteria communications, including those of emerging isolates. PMID:22539957

Benchmarking the pseudopotential and fixed-node approximations in diffusion Monte Carlo calculations of molecules and solids

DOE PAGES

Nazarov, Roman; Shulenburger, Luke; Morales, Miguel A.; ...

2016-03-28

We performed diffusion Monte Carlo (DMC) calculations of the spectroscopic properties of a large set of molecules, assessing the effect of different approximations. In systems containing elements with large atomic numbers, we show that the errors associated with the use of nonlocal mean-field-based pseudopotentials in DMC calculations can be significant and may surpass the fixed-node error. In conclusion, we suggest practical guidelines for reducing these pseudopotential errors, which allow us to obtain DMC-computed spectroscopic parameters of molecules and equation of state properties of solids in excellent agreement with experiment.

Benchmarking the pseudopotential and fixed-node approximations in diffusion Monte Carlo calculations of molecules and solids

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

Nazarov, Roman; Shulenburger, Luke; Morales, Miguel A.

We performed diffusion Monte Carlo (DMC) calculations of the spectroscopic properties of a large set of molecules, assessing the effect of different approximations. In systems containing elements with large atomic numbers, we show that the errors associated with the use of nonlocal mean-field-based pseudopotentials in DMC calculations can be significant and may surpass the fixed-node error. In conclusion, we suggest practical guidelines for reducing these pseudopotential errors, which allow us to obtain DMC-computed spectroscopic parameters of molecules and equation of state properties of solids in excellent agreement with experiment.

Computing Rates of Small Molecule Diffusion Through Protein Channels Using Markovian Milestoning

NASA Astrophysics Data System (ADS)

Abrams, Cameron

2014-03-01

Measuring diffusion rates of ligands plays a key role in understanding the kinetic processes inside proteins. For example, although many molecular simulation studies have reported free energy barriers to infer rates for CO diffusion in myoglobin (Mb), they typically do not include direct calculation of diffusion rates because of the long simulation times needed to infer these rates with statistical accuracy. We show in this talk how to apply Markovian milestoning along minimum free-energy pathways to calculate diffusion rates of CO inside Mb. In Markovian milestoning, one partitions a suitable reaction coordinate space into regions and performs restrained molecular dynamics in each region to accumulate kinetic statistics that, when assembled across regions, provides an estimate of the mean first-passage time between states. The mean escape time for CO directly from the so-called distal pocket (DP) through the histidine gate (HG) is estimated at about 24 ns, confirming the importance of this portal for CO. But Mb is known to contain several internal cavities, and cavity-to-cavity diffusion rates are also computed and used to build a complete kinetic network as a Markov state model. Within this framework, the effective mean time of escape to the solvent through HG increases to 30 ns. Our results suggest that carrier protein structure may have evolved under pressure to modulate dissolved gas release rates using a network of ligand-accessible cavities. Support: NIH R01GM100472.

Diffusion, capture and recycling of SCAR/WAVE and Arp2/3 complexes observed in cells by single-molecule imaging.

PubMed

Millius, Arthur; Watanabe, Naoki; Weiner, Orion D

2012-03-01

The SCAR/WAVE complex drives lamellipodium formation by enhancing actin nucleation by the Arp2/3 complex. Phosphoinositides and Rac activate the SCAR/WAVE complex, but how SCAR/WAVE and Arp2/3 complexes converge at sites of nucleation is unknown. We analyzed the single-molecule dynamics of WAVE2 and p40 (subunits of the SCAR/WAVE and Arp2/3 complexes, respectively) in XTC cells. We observed lateral diffusion of both proteins and captured the transition of p40 from diffusion to network incorporation. These results suggest that a diffusive 2D search facilitates binding of the Arp2/3 complex to actin filaments necessary for nucleation. After nucleation, the Arp2/3 complex integrates into the actin network and undergoes retrograde flow, which results in its broad distribution throughout the lamellipodium. By contrast, the SCAR/WAVE complex is more restricted to the cell periphery. However, with single-molecule imaging, we also observed WAVE2 molecules undergoing retrograde motion. WAVE2 and p40 have nearly identical speeds, lifetimes and sites of network incorporation. Inhibition of actin retrograde flow does not prevent WAVE2 association and disassociation with the membrane but does inhibit WAVE2 removal from the actin cortex. Our results suggest that membrane binding and diffusion expedites the recruitment of nucleation factors to a nucleation site independent of actin assembly, but after network incorporation, ongoing actin polymerization facilitates recycling of SCAR/WAVE and Arp2/3 complexes.

Diffusion, capture and recycling of SCAR/WAVE and Arp2/3 complexes observed in cells by single-molecule imaging

PubMed Central

Millius, Arthur; Watanabe, Naoki; Weiner, Orion D.

2012-01-01

The SCAR/WAVE complex drives lamellipodium formation by enhancing actin nucleation by the Arp2/3 complex. Phosphoinositides and Rac activate the SCAR/WAVE complex, but how SCAR/WAVE and Arp2/3 complexes converge at sites of nucleation is unknown. We analyzed the single-molecule dynamics of WAVE2 and p40 (subunits of the SCAR/WAVE and Arp2/3 complexes, respectively) in XTC cells. We observed lateral diffusion of both proteins and captured the transition of p40 from diffusion to network incorporation. These results suggest that a diffusive 2D search facilitates binding of the Arp2/3 complex to actin filaments necessary for nucleation. After nucleation, the Arp2/3 complex integrates into the actin network and undergoes retrograde flow, which results in its broad distribution throughout the lamellipodium. By contrast, the SCAR/WAVE complex is more restricted to the cell periphery. However, with single-molecule imaging, we also observed WAVE2 molecules undergoing retrograde motion. WAVE2 and p40 have nearly identical speeds, lifetimes and sites of network incorporation. Inhibition of actin retrograde flow does not prevent WAVE2 association and disassociation with the membrane but does inhibit WAVE2 removal from the actin cortex. Our results suggest that membrane binding and diffusion expedites the recruitment of nucleation factors to a nucleation site independent of actin assembly, but after network incorporation, ongoing actin polymerization facilitates recycling of SCAR/WAVE and Arp2/3 complexes. PMID:22349699

Thermophoresis of a Brownian particle driven by inhomogeneous thermal fluctuation

NASA Astrophysics Data System (ADS)

Tsuji, Tetsuro; Saita, Sho; Kawano, Satoyuki

2018-03-01

Brownian motion of a spherical particle induced by the interaction with surrounding molecules is considered. If the particle is larger than the molecules and the temperature of surrounding media is spatially non-uniform, the interaction between an individual molecule and the particle is also position-dependent. That is, the particle is subject to inhomogeneous thermal fluctuation. In this paper, we investigate the contribution of the inhomogeneous thermal fluctuation to the thermophoresis, i.e., the Soret coefficient or thermal diffusion factor. The problem is simplified by assuming a hard-sphere potential between the particle and the surrounding molecules and is investigated using the kinetic theory, namely, we consider a linear Boltzmann-type equation for the velocity distribution function of the particle. Using the perturbation analysis with respect to the square root of mass ratio between the molecule and the particle, the drift-diffusion equation of the particle is derived. It is found that the Soret coefficient, or thermal diffusion factor, is dependent on the mass ratio and the excluded volume of the particle. In particular, when the ratio of the mass density of the particle to that of the surrounding media decreases, the Soret coefficient also decreases and may take negative value. The present result well describes the mass-dependency of thermal diffusion factor obtained by the molecular dynamics simulation carried out in an existing study and the one in the present study, where soft potentials of Lennard-Jones-type are used instead of hard-sphere potential.

Applications of a general random-walk theory for confined diffusion.

PubMed

Calvo-Muñoz, Elisa M; Selvan, Myvizhi Esai; Xiong, Ruichang; Ojha, Madhusudan; Keffer, David J; Nicholson, Donald M; Egami, Takeshi

2011-01-01

A general random walk theory for diffusion in the presence of nanoscale confinement is developed and applied. The random-walk theory contains two parameters describing confinement: a cage size and a cage-to-cage hopping probability. The theory captures the correct nonlinear dependence of the mean square displacement (MSD) on observation time for intermediate times. Because of its simplicity, the theory also requires modest computational requirements and is thus able to simulate systems with very low diffusivities for sufficiently long time to reach the infinite-time-limit regime where the Einstein relation can be used to extract the self-diffusivity. The theory is applied to three practical cases in which the degree of order in confinement varies. The three systems include diffusion of (i) polyatomic molecules in metal organic frameworks, (ii) water in proton exchange membranes, and (iii) liquid and glassy iron. For all three cases, the comparison between theory and the results of molecular dynamics (MD) simulations indicates that the theory can describe the observed diffusion behavior with a small fraction of the computational expense. The confined-random-walk theory fit to the MSDs of very short MD simulations is capable of accurately reproducing the MSDs of much longer MD simulations. Furthermore, the values of the parameter for cage size correspond to the physical dimensions of the systems and the cage-to-cage hopping probability corresponds to the activation barrier for diffusion, indicating that the two parameters in the theory are not simply fitted values but correspond to real properties of the physical system.

Effects of molecular size and structure on self-diffusion coefficient and viscosity for saturated hydrocarbons having six carbon atoms.

PubMed

Iwahashi, Makio; Kasahara, Yasutoshi

2007-01-01

Self-diffusion coefficients and viscosities for the saturated hydrocarbons having six carbon atoms such as hexane, 2-methylpentane (2MP), 3-methylpentane (3MP), 2,2-dimethylbutane (22DMB), 2,3-dimethylbutane (23DMB), methylcyclopentane (McP) and cyclohexane (cH) were measured at various constant temperatures; obtained results were discussed in connection with their molar volumes, molecular structures and thermodynamic properties. The values of self-diffusion coefficients as the microscopic property were inversely proportional to those of viscosities as the macroscopic property. The order of their viscosities was almost same to those of their melting temperatures and enthalpies of fusion, which reflect the attractive interactions among their molecules. On the other hand, the order of the self-diffusion coefficients inversely related to the order of the melting temperatures and the enthalpies of the fusion. Namely, the compound having the larger attractive interaction mostly shows the less mobility in its liquid state, e.g., cyclohexane (cH), having the largest attractive interaction and the smallest molar volume exhibits an extremely large viscosity and small self-diffusion coefficient comparing with other hydrocarbons. However, a significant exception was 22DMB, being most close to a sphere: In spite of the smallest attractive interaction and the largest molar volume of 22DMB in the all samples, it has the thirdly larger viscosity and the thirdly smaller self-diffusion coefficient. Consequently, the dynamical properties such as self-diffusion and viscosity for the saturated hydrocarbons are determined not only by their attractive interactions but also by their molecular structures.

Solute diffusion in liquid metals

NASA Technical Reports Server (NTRS)

Bhat, B. N.

1973-01-01

A gas model of diffusion in liquid metals is presented. In this model, ions of liquid metals are assumed to behave like the molecules in a dense gas. Diffusion coefficient of solute is discussed with reference to its mass, ionic size, and pair potential. The model is applied to the case of solute diffusion in liquid silver. An attempt was made to predict diffusion coefficients of solutes with reasonable accuracy.

Self diffusion of interacting membrane proteins.

PubMed Central

Abney, J R; Scalettar, B A; Owicki, J C

1989-01-01

A two-dimensional version of the generalized Smoluchowski equation is used to analyze the time (or distance) dependent self diffusion of interacting membrane proteins in concentrated membrane systems. This equation provides a well established starting point for descriptions of the diffusion of particles that interact through both direct and hydrodynamic forces; in this initial work only the effects of direct interactions are explicitly considered. Data describing diffusion in the presence of hard-core repulsions, soft repulsions, and soft repulsions with weak attractions are presented. The effect that interactions have on the self-diffusion coefficient of a real protein molecule from mouse liver gap junctions is also calculated. The results indicate that self diffusion is always inhibited by direct interactions; this observation is interpreted in terms of the caging that will exist at finite protein concentration. It is also noted that, over small distance scales, the diffusion coefficient is determined entirely by the very strong Brownian forces; therefore, as a function of displacement the self-diffusion coefficient decays (rapidly) from its value at infinite dilution to its steady-state interaction-averaged value. The steady-state self-diffusion coefficient describes motion over distance scales that range from approximately 10 nm to cellular dimensions and is the quantity measured in fluorescence recovery after photobleaching experiments. The short-ranged behavior of the diffusion coefficient is important on the interparticle-distance scale and may therefore influence the rate at which nearest-neighbor collisional processes take place. The hard-disk theoretical results presented here are in excellent agreement with lattice Monte-Carlo results obtained by other workers. The concentration dependence of experimentally measured diffusion coefficients of antibody-hapten complexes bound to the membrane surface is consistent with that predicted by the theory. The variation in experimental diffusion coefficients of integral membrane proteins is greater than that predicted by the theory, and may also reflect protein-induced perturbations in membrane viscosity. PMID:2720077

Concentration-Encoded Subdiffusive Molecular Communication: Theory, Channel Characteristics, and Optimum Signal Detection.

PubMed

Mahfuz, Mohammad Upal; Makrakis, Dimitrios; Mouftah, Hussein T

2016-09-01

Unlike normal diffusion, in anomalous diffusion, the movement of a molecule is described by the correlated random walk model where the mean square displacement of a molecule depends on the power law of time. In molecular communication (MC), there are many scenarios when the propagation of molecules cannot be described by normal diffusion process, where anomalous diffusion is a better fit. In this paper, the effects of anomalous subdiffusion on concentration-encoded molecular communication (CEMC) are investigated. Although classical (i.e., normal) diffusion is a widely-used model of diffusion in molecular communication (MC) research, anomalous subdiffusion is quite common in biological media involving bio-nanomachines, yet inadequately addressed as a research issue so far. Using the fractional diffusion approach, the molecular propagation effects in the case of pure subdiffusion occurring in an unbounded three-dimensional propagation medium have been shown in detail in terms of temporal dispersion parameters of the impulse response of the subdiffusive channel. Correspondingly, the bit error rate (BER) performance of a CEMC system is investigated with sampling-based (SD) and strength (i.e., energy)-based (ED) signal detection methods. It is found that anomalous subdiffusion has distinctive time-dispersive properties that play a vital role in accurately designing a subdiffusive CEMC system. Unlike normal diffusion, to detect information symbols in subdiffusive CEMC, a receiver requires larger memory size to operate correctly and hence a more complex structure. An in-depth analysis has been made on the performances of SD and ED optimum receiver models under diffusion noise and intersymbol interference (ISI) scenarios when communication range, transmission data rate, and memory size vary. In subdiffusive CEMC, the SD method.

Transport Mechanism of Guest Methane in Water-Filled Nanopores

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

Bui, Tai; Phan, Anh; Cole, David R.

We computed the transport of methane through 1 nm wide slit-shaped pores carved out of selected solid substrates using classical molecular dynamics simulations. The transport mechanism was elucidated via the implementation of the well-tempered metadynamics algorithm, which allowed for the quantification and visualization of the free energy landscape sampled by the guest molecule. Models for silica, magnesium oxide, alumina, muscovite, and calcite were used as solid substrates. Slit-shaped pores of width 1 nm were carved out of these materials and filled with liquid water. Methane was then inserted at low concentration. The results show that the diffusion of methane throughmore » the hydrated pores is strongly dependent on the solid substrate. While methane molecules diffuse isotropically along the directions parallel to the pore surfaces in most of the pores considered, anisotropic diffusion was observed in the hydrated calcite pore. The differences observed in the various pores are due to local molecular properties of confined water, including molecular structure and solvation free energy. The transport mechanism and the diffusion coefficients are dependent on the free energy barriers encountered by one methane molecule as it migrates from one preferential adsorption site to a neighboring one. It was found that the heterogeneous water distribution in different hydration layers and the low free energy pathways in the plane parallel to the pore surfaces yield the anisotropic diffusion of methane molecules in the hydrated calcite pore. Our observations contribute to an ongoing debate on the relation between local free energy profiles and diffusion coefficients and could have important practical consequences in various applications, ranging from the design of selective membranes for gas separations to the sustainable deployment of shale gas.« less

Transport Mechanism of Guest Methane in Water-Filled Nanopores

DOE PAGES

Bui, Tai; Phan, Anh; Cole, David R.; ...

2017-05-11

We computed the transport of methane through 1 nm wide slit-shaped pores carved out of selected solid substrates using classical molecular dynamics simulations. The transport mechanism was elucidated via the implementation of the well-tempered metadynamics algorithm, which allowed for the quantification and visualization of the free energy landscape sampled by the guest molecule. Models for silica, magnesium oxide, alumina, muscovite, and calcite were used as solid substrates. Slit-shaped pores of width 1 nm were carved out of these materials and filled with liquid water. Methane was then inserted at low concentration. The results show that the diffusion of methane throughmore » the hydrated pores is strongly dependent on the solid substrate. While methane molecules diffuse isotropically along the directions parallel to the pore surfaces in most of the pores considered, anisotropic diffusion was observed in the hydrated calcite pore. The differences observed in the various pores are due to local molecular properties of confined water, including molecular structure and solvation free energy. The transport mechanism and the diffusion coefficients are dependent on the free energy barriers encountered by one methane molecule as it migrates from one preferential adsorption site to a neighboring one. It was found that the heterogeneous water distribution in different hydration layers and the low free energy pathways in the plane parallel to the pore surfaces yield the anisotropic diffusion of methane molecules in the hydrated calcite pore. Our observations contribute to an ongoing debate on the relation between local free energy profiles and diffusion coefficients and could have important practical consequences in various applications, ranging from the design of selective membranes for gas separations to the sustainable deployment of shale gas.« less

Solution structure of biopolymers: a new method of constructing a bead model.

PubMed Central

Banachowicz, E; Gapiński, J; Patkowski, A

2000-01-01

We propose a new, automated method of converting crystallographic data into a bead model used for the calculations of hydrodynamic properties of rigid macromolecules. Two types of molecules are considered: nucleic acids and small proteins. A bead model of short DNA fragments has been constructed in which each nucleotide is represented by two identical, partially overlapping spheres: one for the base and one for the sugar and phosphate group. The optimum radius sigma = 5.0 A was chosen on the basis of a comparison of the calculated translational diffusion coefficients (D(T)) and the rotational relaxation times (tau(R)) with the corresponding experimental data for B-DNA fragments of 8, 12, and 20 basepairs. This value was assumed for the calculation D(T) and tau(R) of tRNA(Phe). Better agreement with the experimental data was achieved for slightly larger sigma = 5.7 A. A similar procedure was applied to small proteins. Bead models were constructed such that each amino acid was represented by a single sphere or a pair of identical, partially overlapping spheres, depending on the amino acid's size. Experimental data of D(T) of small proteins were used to establish the optimum value of sigma = 4.5 A for amino acids. The lack of experimental data on tau(R) for proteins restricted the tests to the translational diffusion properties. PMID:10620274

Combined effects of the drug distribution and mucus diffusion properties of self-microemulsifying drug delivery systems on the oral absorption of fenofibrate.

PubMed

Sunazuka, Yushi; Ueda, Keisuke; Higashi, Kenjirou; Tanaka, Yusuke; Moribe, Kunikazu

2018-05-24

We present the absorption improvement mechanism of fenofibrate (FFB), a Biopharmaceutics Classification System (BCS) class II drug, from self-microemulsifying drug delivery systems (SMEDDS), centered on improving the diffusion of FFB through the unstirred water layer (UWL). Four SMEDDS formulations containing Labrafac™ lipophile WL 1349 (WL1349) or Labrafil ® M 1944CS (M1944) oils and NIKKOL HCO-40 (HCO40) or NIKKOL HCO-60 (HCO60) surfactants were prepared. Every SMEDDS formulation formed microemulsion droplets of approximately 30 nm. In vitro tests showed that the microemulsion droplets containing M1944 had relatively small FFB solubilization capacities, causing larger amounts of FFB to be dissolved in the bulk water phase, compared to the droplets containing WL1349. The diffusivity of the microemulsion droplets through the mucin solution layer was enhanced when using HCO40 compared to HCO60. The oral absorption in rats was the highest when using the SMEDDS formulation containing M1944 and HCO40. High FFB distribution in the bulk water phase and fast diffusion of microemulsion droplets through the mucus layer contributed to the efficient delivery of FFB molecules through the UWL to the epithelial cells, leading to enhanced FFB absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

Compartmentalization of the outer hair cell demonstrated by slow diffusion in the extracisternal space.

PubMed

Gliko, Olga; Saggau, Peter; Brownell, William E

2009-08-19

In the outer hair cell (OHC), the extracisternal space (ECiS) is a conduit and reservoir of the molecular and ionic substrates of the lateral wall, including those necessary for electromotility. To determine the mechanisms through which molecules are transported in the ECiS of the OHC, we selectively imaged the time-dependent spatial distribution of fluorescent molecules in a <100 nm layer near the cell/glass interface of the recording chamber after their photolytic activation in a diffraction-limited volume. The effective diffusion coefficient was calculated using the analytical solution of the diffusion equation. It was found that diffusion in the ECiS is isotropic and not affected by depolarizing the OHC. Compared with free solution, the diffusion of 10 kDa dextran was slowed down in both the ECiS and the axial core by a factor of 4.6 and 1.6, respectively.

Diffusion of gas mixtures in the sI hydrate structure

NASA Astrophysics Data System (ADS)

Waage, Magnus H.; Trinh, Thuat T.; van Erp, Titus S.

2018-06-01

Replacing methane with carbon dioxide in gas hydrates has been suggested as a way of harvesting methane, while at the same time storing carbon dioxide. Experimental evidence suggests that this process is facilitated if gas mixtures are used instead of pure carbon dioxide. We studied the free energy barriers for diffusion of methane, carbon dioxide, nitrogen, and hydrogen in the sI hydrate structure using molecular simulation techniques. Cage hops between neighboring cages were considered with and without a water vacancy and with a potential inclusion of an additional gas molecule in either the initial or final cage. Our results give little evidence for enhanced methane and carbon dioxide diffusion if nitrogen is present as well. However, the inclusion of hydrogen seems to have a substantial effect as it diffuses rapidly and can easily enter occupied cages, which reduces the barriers of diffusion for the gas molecules that co-occupy a cage with hydrogen.

The effects of bound state motion on macromolecular diffusion

NASA Astrophysics Data System (ADS)

Hough, Loren; Stefferson, Michael; Norris, Samantha; Maguire, Laura; Vernerey, Franck; Betterton, Meredith

The diffusion of macromolecules is modified in crowded environments by both inert obstacles and interaction sites. Molecules are generally slowed in their movement inducing transient anomalous subdiffusion. Obstacles also modify the kinetics and equilibrium behavior of interaction between mobile proteins. In some biophysical contexts, bound molecules can still experience mobility, for example transcription factors sliding along DNA, membrane proteins with some entry and diffusion within lipid domains, or proteins that can enter into non-membrane bound compartments such as the nucleolus. We used lattice and continuum models to study the diffusive behavior of tracer particles which bind to obstacles and can diffuse within them. We show that binding significantly alters the motion of tracers. The type and degree of motion while bound is a key determinant of the tracer mobility. Our work has implications for protein-protein movement and interactions within living cells, including those involving intrinsically disordered proteins.

Real-space analysis of diffusion behavior and activation energy of individual monatomic ions in a liquid.

PubMed

Miyata, Tomohiro; Uesugi, Fumihiko; Mizoguchi, Teruyasu

2017-12-01

Investigation of the local dynamic behavior of atoms and molecules in liquids is crucial for revealing the origin of macroscopic liquid properties. Therefore, direct imaging of single atoms to understand their motions in liquids is desirable. Ionic liquids have been studied for various applications, in which they are used as electrolytes or solvents. However, atomic-scale diffusion and relaxation processes in ionic liquids have never been observed experimentally. We directly observe the motion of individual monatomic ions in an ionic liquid using scanning transmission electron microscopy (STEM) and reveal that the ions diffuse by a cage-jump mechanism. Moreover, we estimate the diffusion coefficient and activation energy for the diffusive jumps from the STEM images, which connect the atomic-scale dynamics to macroscopic liquid properties. Our method is the only available means to observe the motion, reactions, and energy barriers of atoms/molecules in liquids.

Multiphoton microscopy guides neurotrophin modification with poly(ethylene glycol) to enhance interstitial diffusion

NASA Astrophysics Data System (ADS)

Stroh, Mark; Zipfel, Warren R.; Williams, Rebecca M.; Ma, Shu Chin; Webb, Watt W.; Saltzman, W. Mark

2004-07-01

Brain-derived neurotrophic factor (BDNF) is a promising therapeutic agent for the treatment of neurodegenerative diseases. However, the limited distribution of this molecule after administration into the brain tissue considerably hampers its efficacy. Here, we show how multiphoton microscopy of fluorescently tagged BDNF in brain-tissue slices provides a useful and rapid screening method for examining the diffusion of large molecules in tissues, and for studying the effects of chemical modifications-for example, conjugating with polyethylene glycol (PEG)-on the diffusion constant. This single variable, obtained by monitoring short-term diffusion in real time, can be effectively used for rational drug design. In this study on fluorescently tagged BDNF and BDNF-PEG, we identify slow diffusion as a major contributing factor to the limited penetration of BDNF, and demonstrate how chemical modification can be used to overcome this barrier.

Diffusion MRI at 25: Exploring brain tissue structure and function

PubMed Central

Bihan, Denis Le; Johansen-Berg, Heidi

2013-01-01

Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state. PMID:22120012

Nanoscopic compartmentalization of membrane protein motion at the axon initial segment.

PubMed

Albrecht, David; Winterflood, Christian M; Sadeghi, Mohsen; Tschager, Thomas; Noé, Frank; Ewers, Helge

2016-10-10

The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development. We analyzed the mobility of lipid-anchored molecules by high-speed single-particle tracking and correlated positions of membrane molecules with the nanoscopic organization of the AIS cytoskeleton. We observe a strong reduction in mobility early in AIS development. Membrane protein motion in the AIS plasma membrane is confined to a repetitive pattern of ∼190-nm-spaced segments along the AIS axis as early as day in vitro 4, and this pattern alternates with actin rings. Mathematical modeling shows that diffusion barriers between the segments significantly reduce lateral diffusion along the axon. © 2016 Albrecht et al.

Spatially Different Tissue-Scale Diffusivity Shapes ANGUSTIFOLIA3 Gradient in Growing Leaves.

PubMed

Kawade, Kensuke; Tanimoto, Hirokazu; Horiguchi, Gorou; Tsukaya, Hirokazu

2017-09-05

The spatial gradient of signaling molecules is pivotal for establishing developmental patterns of multicellular organisms. It has long been proposed that these gradients could arise from the pure diffusion process of signaling molecules between cells, but whether this simplest mechanism establishes the formation of the tissue-scale gradient remains unclear. Plasmodesmata are unique channel structures in plants that connect neighboring cells for molecular transport. In this study, we measured cellular- and tissue-scale kinetics of molecular transport through plasmodesmata in Arabidopsis thaliana developing leaf primordia by fluorescence recovery assays. These trans-scale measurements revealed biophysical properties of diffusive molecular transport through plasmodesmata and revealed that the tissue-scale diffusivity, but not the cellular-scale diffusivity, is spatially different along the leaf proximal-to-distal axis. We found that the gradient in cell size along the developmental axis underlies this spatially different tissue-scale diffusivity. We then asked how this diffusion-based framework functions in establishing a signaling gradient of endogenous molecules. ANGUSTIFOLIA3 (AN3) is a transcriptional co-activator, and as we have shown here, it forms a long-range signaling gradient along the leaf proximal-to-distal axis to determine a cell-proliferation domain. By genetically engineering AN3 mobility, we assessed each contribution of cell-to-cell movement and tissue growth to the distribution of the AN3 gradient. We constructed a diffusion-based theoretical model using these quantitative data to analyze the AN3 gradient formation and demonstrated that it could be achieved solely by the diffusive molecular transport in a growing tissue. Our results indicate that the spatially different tissue-scale diffusivity is a core mechanism for AN3 gradient formation. This provides evidence that the pure diffusion process establishes the formation of the long-range signaling gradient in leaf development. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Molecular targets for small-molecule modulators of circadian clocks

PubMed Central

He, Baokun; Chen, Zheng

2016-01-01

Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

Adsorption and diffusion of fructose in zeolite HZSM-5: selection of models and methods for computational studies.

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

Cheng, L.; Curtiss, L. A.; Assary, R. S.

The adsorption and protonation of fructose in HZSM-5 have been studied for the assessment of models for accurate reaction energy calculations and the evaluation of molecular diffusivity. The adsorption and protonation were calculated using 2T, 5T, and 46T clusters as well as a periodic model. The results indicate that the reaction thermodynamics cannot be predicted correctly using small cluster models, such as 2T or 5T, because these small cluster models fail to represent the electrostatic effect of a zeolite cage, which provides additional stabilization to the ion pair formed upon the protonation of fructose. Structural parameters optimized using the 46Tmore » cluster model agree well with those of the full periodic model; however, the calculated reaction energies are in significant error due to the poor account of dispersion effects by density functional theory. The dispersion effects contribute -30.5 kcal/mol to the binding energy of fructose in the zeolite pore based on periodic model calculations that include dispersion interactions. The protonation of the fructose ternary carbon hydroxyl group was calculated to be exothermic by 5.5 kcal/mol with a reaction barrier of 2.9 kcal/mol using the periodic model with dispersion effects. Our results suggest that the internal diffusion of fructose in HZSM-5 is very likely to be energetically limited and only occurs at high temperature due to the large size of the molecule.« less

Adsorption and Diffusion of Fructose in Zeolite HZSM-5: Selection of Models and Methods for Computational Studies

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

Cheng, Lei; Curtiss, Larry A.; Assary, Rajeev S.

The adsorption and protonation of fructose inHZSM-5 have been studied for the assessment of models for accurate reaction energy calculations and the evaluation of molecular diffusivity. The adsorption and protonation were calculated using 2T, 5T, and 46T clusters as well as a periodic model. The results indicate that the reaction thermodynamics cannot be predicted correctly using small cluster models, such as 2T or 5T, because these small cluster models fail to represent the electrostatic effect of a zeolite cage, which provides additional stabilization to the ion pair formed upon the protonation of fructose. Structural parameters optimized using the 46T clustermore » model agree well with those of the full periodic model; however, the calculated reaction energies are in significant error due to the poor account of dispersion effects by density functional theory. The dispersion effects contribute -30.5 kcal/mol to the binding energy of fructose in the zeolite pore based on periodic model calculations that include dispersion interactions. The protonation of the fructose ternary carbon hydroxyl group was calculated to be exothermic by 5.5 kcal/mol with a reaction barrier of 2.9 kcal/mol using the periodic model with dispersion effects. Our results suggest that the internal diffusion of fructose in HZSM-5 is very likely to be energetically limited and only occurs at high temperature due to the large size of the molecule.« less

Molecular motion in cell membranes: Analytic study of fence-hindered random walks

NASA Astrophysics Data System (ADS)

Kenkre, V. M.; Giuggioli, L.; Kalay, Z.

2008-05-01

A theoretical calculation is presented to describe the confined motion of transmembrane molecules in cell membranes. The study is analytic, based on Master equations for the probability of the molecules moving as random walkers, and leads to explicit usable solutions including expressions for the molecular mean square displacement and effective diffusion constants. One outcome is a detailed understanding of the dependence of the time variation of the mean square displacement on the initial placement of the molecule within the confined region. How to use the calculations is illustrated by extracting (confinement) compartment sizes from experimentally reported published observations from single particle tracking experiments on the diffusion of gold-tagged G -protein coupled μ -opioid receptors in the normal rat kidney cell membrane, and by further comparing the analytical results to observations on the diffusion of phospholipids, also in normal rat kidney cells.

Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.

PubMed

Yu, Shuizi Rachel; Burkhardt, Markus; Nowak, Matthias; Ries, Jonas; Petrásek, Zdenek; Scholpp, Steffen; Schwille, Petra; Brand, Michael

2009-09-24

It is widely accepted that tissue differentiation and morphogenesis in multicellular organisms are regulated by tightly controlled concentration gradients of morphogens. How exactly these gradients are formed, however, remains unclear. Here we show that Fgf8 morphogen gradients in living zebrafish embryos are established and maintained by two essential factors: fast, free diffusion of single molecules away from the source through extracellular space, and a sink function of the receiving cells, regulated by receptor-mediated endocytosis. Evidence is provided by directly examining single molecules of Fgf8 in living tissue by fluorescence correlation spectroscopy, quantifying their local mobility and concentration with high precision. By changing the degree of uptake of Fgf8 into its target cells, we are able to alter the shape of the Fgf8 gradient. Our results demonstrate that a freely diffusing morphogen can set up concentration gradients in a complex multicellular tissue by a simple source-sink mechanism.

Markov Chain Monte Carlo in the Analysis of Single-Molecule Experimental Data

NASA Astrophysics Data System (ADS)

Kou, S. C.; Xie, X. Sunney; Liu, Jun S.

2003-11-01

This article provides a Bayesian analysis of the single-molecule fluorescence lifetime experiment designed to probe the conformational dynamics of a single DNA hairpin molecule. The DNA hairpin's conformational change is initially modeled as a two-state Markov chain, which is not observable and has to be indirectly inferred. The Brownian diffusion of the single molecule, in addition to the hidden Markov structure, further complicates the matter. We show that the analytical form of the likelihood function can be obtained in the simplest case and a Metropolis-Hastings algorithm can be designed to sample from the posterior distribution of the parameters of interest and to compute desired estiamtes. To cope with the molecular diffusion process and the potentially oscillating energy barrier between the two states of the DNA hairpin, we introduce a data augmentation technique to handle both the Brownian diffusion and the hidden Ornstein-Uhlenbeck process associated with the fluctuating energy barrier, and design a more sophisticated Metropolis-type algorithm. Our method not only increases the estimating resolution by several folds but also proves to be successful for model discrimination.

Addition of perfluorocarbons to alginate hydrogels significantly impacts molecular transport and fracture stress.

PubMed

White, Joseph C; Stoppel, Whitney L; Roberts, Susan C; Bhatia, Surita R

2013-02-01

Perfluorocarbons (PFCs) are used in biomaterial formulations to increase oxygen (O(2) ) tension and create a homogeneous O(2) environment in three-dimensional tissue constructs. It is unclear how PFCs affect mechanical and transport properties of the scaffold, which are critical for robustness, intracellular signaling, protein transport, and overall device efficacy. In this study, we investigate composite alginate hydrogels containing a perfluorooctyl bromide (PFOB) emulsion stabilized with Pluronic(®) F68 (F68). We demonstrate that PFC addition significantly affects biomaterial properties and performance. Solution and hydrogel mechanical properties and transport of representative hydrophilic (riboflavin), hydrophobic (methyl and ethyl paraben), and protein (bovine serum albumin, BSA) solutes were compared in alginate/F68 composite hydrogels with or without PFOB. Our results indicate that mechanical properties of the alginate/F68/PFOB hydrogels are not significantly affected under small strains, but a significant decrease fracture stress is observed. The effective diffusivity D(eff) of hydrophobic small molecules decreases with PFOB emulsion addition, yet the D(eff) of hydrophilic small molecules remained unaffected. For BSA, the D(eff) increased and the loading capacity decreased with PFOB emulsion addition. Thus, a trade-off between the desired increased O(2) supply provided by PFCs and the mechanical weakening and change in transport of cellular signals must be carefully considered in the design of biomaterials containing PFCs. Copyright © 2012 Wiley Periodicals, Inc.

Fabrication and characterization of controllable grain boundary arrays in solution-processed small molecule organic semiconductor films

NASA Astrophysics Data System (ADS)

Wo, Songtao; Headrick, Randall L.; Anthony, John E.

2012-04-01

We have produced solution-processed thin films of 6,13-bis(tri-isopropyl-silylethynyl) pentacene with grain sizes from a few micrometers up to millimeter scale by lateral crystallization from a rectangular stylus. Grains are oriented along the crystallization direction, and the grain size transverse to the crystallization direction depends inversely on the writing speed, hence forming a regular array of oriented grain boundaries with controllable spacing. We utilize these controllable arrays to systematically study the role of large-angle grain boundaries in carrier transport and charge trapping in thin film transistors. The effective mobility scales with the grain size, leading to an estimate of the potential drop at individual large-angle grain boundaries of more than 1 volt. This result indicates that the structure of grain boundaries is not molecularly abrupt, which may be a general feature of solution-processed small molecule organic semiconductor thin films, where relatively high energy grain boundaries are typically formed. Transient measurements after switching from positive to negative gate bias or between large and small negative gate bias reveal reversible charge trapping, with time constants on the order of 10 s and trap densities that are correlated with grain boundary density. We suggest that charge diffusion along grain boundaries and other defects is the rate-determining mechanism of the reversible trapping.

Formation and stability of synaptic receptor domains.

PubMed

Haselwandter, Christoph A; Calamai, Martino; Kardar, Mehran; Triller, Antoine; da Silveira, Rava Azeredo

2011-06-10

Neurotransmitter receptor molecules, concentrated in postsynaptic domains along with scaffold and a number of other molecules, are key regulators of signal transmission across synapses. Combining experiment and theory, we develop a quantitative description of synaptic receptor domains in terms of a reaction-diffusion model. We show that interactions between only receptors and scaffolds, together with the rapid diffusion of receptors on the cell membrane, are sufficient for the formation and stable characteristic size of synaptic receptor domains. Our work reconciles long-term stability of synaptic receptor domains with rapid turnover and diffusion of individual receptors, and suggests novel mechanisms for a form of short-term, postsynaptic plasticity.

Recent advances in developing small molecules targeting RNA.

PubMed

Guan, Lirui; Disney, Matthew D

2012-01-20

RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void.

Diffusion properties of NAA in human corpus callosum as studied with diffusion tensor spectroscopy.

PubMed

Upadhyay, Jaymin; Hallock, Kevin; Erb, Kelley; Kim, Dae-Shik; Ronen, Itamar

2007-11-01

In diffusion tensor imaging (DTI) the anisotropic movement of water is exploited to characterize microstructure. One confounding issue of DTI is the presence of intra- and extracellular components contributing to the measured diffusivity. This causes an ambiguity in determining the underlying cause of diffusion properties, particularly the fractional anisotropy (FA). In this study an intracellular constituent, N-acetyl aspartate (NAA), was used to probe intracellular diffusion, while water molecules were used to probe the combined intra- and extracellular diffusion. NAA and water diffusion measurements were made in anterior and medial corpus callosum (CC) regions, which are referred to as R1 and R2, respectively. FA(NAA) was found to be greater than FA(Water) in both CC regions, thus indicating a higher degree of anisotropy within the intracellular space in comparison to the combined intra- and extracellular spaces. A decreasing trend in the FA of NAA and water was observed between R1 and R2, while the radial diffusivity (RD) for both molecules increased. The increase in RD(NAA) is particularly significant, thus explaining the more significant decrease in FA(NAA) between the two regions. It is suggested that diffusion tensor spectroscopy of NAA can potentially be used to further characterize microscopic anatomic organization in white matter. Copyright 2007 Wiley-Liss, Inc.

The Use of Ultrashort Picosecond Laser Pulses to Generate Quantum Optical Properties of Single Molecules in Biophysics

NASA Astrophysics Data System (ADS)

Ly, Sonny

Generation of quantum optical states from ultrashort laser-molecule interactions have led to fascinating discoveries in physics and chemistry. In recent years, these interactions have been extended to probe phenomena in single molecule biophysics. Photons emitted from a single fluorescent molecule contains important properties about how the molecule behave and function in that particular environment. Analysis of the second order coherence function through fluorescence correlation spectroscopy plays a pivotal role in quantum optics. At very short nanosecond timescales, the coherence function predicts photon antibunching, a purely quantum optical phenomena which states that a single molecule can only emit one photon at a time. Photon antibunching is the only direct proof of single molecule emission. From the nanosecond to microsecond timescale, the coherence function gives information about rotational diffusion coefficients, and at longer millisecond timescales, gives information regarding the translational diffusion coefficients. In addition, energy transfer between molecules from dipole-dipole interaction results in FRET, a highly sensitive method to probe conformational dynamics at nanometer distances. Here I apply the quantum optical techniques of photon antibunching, fluorescence correlation spectroscopy and FRET to probe how lipid nanodiscs form and function at the single molecule level. Lipid nanodiscs are particles that contain two apolipoprotein (apo) A-I circumventing a lipid bilayer in a belt conformation. From a technological point of view, nanodiscs mimics a patch of cell membrane that have recently been used to reconstitute a variety of membrane proteins including cytochrome P450 and bacteriorhodopsin. They are also potential drug transport vehicles due to its small and stable 10nm diameter size. Biologically, nanodiscs resemble to high degree, high density lipoproteins (HDL) in our body and provides a model platform to study lipid-protein interactions and their dynamic formation to lipoprotein particles without having to extract from human blood plasma. Although HDL has been studied extensively within the last thirty years, many questions still remain regarding the structure of apoA-I, the protein associated exclusively with it. Despite our ability to detect and image these nanodiscs by blotting, atomic force microscopy (AFM), or electron microscopy (EM), many basic properties such as their specific hydrated shape in solution, or the precise conformation of the apolipoproteins surrounding the particles are still unknown. The dynamic interactions of apoA-I with lipids are also rather poorly understood on a fundamental level, and are only characterized in bulk (biochemical blotting) or stationary methods (AFM, EM), making it impossible to study individual steps with high spatial or temporal resolution.

Elementary kinematical model of thermal diffusion in liquids and gases.

PubMed

Brenner, Howard

2006-09-01

An elementary hydrodynamic and Brownian motion model of the thermal diffusivity D(T) of a restricted class of binary liquid mixtures, previously proposed by the author, is given a more transparent derivation than originally, exposing thereby the strictly kinematic-hydrodynamic nature of an important class of thermodiffusion separation phenomena. Moreover, it is argued that the solvent's thermometric diffusivity alpha appearing in that theory as one of the two fundamental parameters governing D(T) should be replaced by the solvent's (isothermal) self-diffusivity D(S). In addition, a corrective multiplier of O(1) is inserted to reflect the general physicochemical noninertness of the solute relative to the solvent, thus enhancing the applicability of the resulting formula D(T)=lambdaD(S)beta to "nonideal" solutions. Here, beta is the solvent's thermal expansivity and lambda is a term of O(1), insensitive to the physicochemical nature of the solute (thus rendering D(T) primarily dependent upon only the properties of the solvent). This formula is, on the basis of its derivation, presumably valid only under certain idealized, albeit well-defined, circumstances. This occurs when the solute molecules are: (i) large compared with those of the solvent; and (ii) present only in small proportions relative to those of the solvent. When the solute is physicochemically inert, it is expected that lambda=1. When these conditions are met, the resulting thermal diffusivity of the mixture is, in theory, independent of any and all properties of the solute. Moreover, because beta is algebraically signed, the thermal diffusivity can either by positive or negative, according as the solvent expands or contracts upon being heated. This formula for D(T) is compared with available experimental data for selected binary liquid mixtures. Reasonable agreement is found in almost all circumstances with lambda near unity, the more so the higher the temperature, especially when the solute-solvent mixture properties closely approximate those where agreement would be expected and conversely. Finally, it is pointed out that for the restricted circumstances described, the formula D(T)=lambdaD(S)beta is equally credible for gases. Here, based on gas-kinetic theory, it is possible to furnish the theoretical value of lambda. Overall, while spanning a range of about five orders of magnitude, the D(T) values given by this elementary formula are shown to apply with reasonable accuracy to: (i) liquids (including circumstances for which D(T) is negative) as well as gases; (ii) all combinations of solvents and solutes tested (the latter including, for example, polymer molecules and metallic colloidal particles); and (iii) all sizes of solute molecules, from angstroms to submicron.

Observations and Analysis of Extended Tail Toward Red in the Diffuse Interstellar Bands of Herschel 36

NASA Astrophysics Data System (ADS)

Oka, Takeshi; Welty, Daniel E.; Johnson, Sean; York, Donald G.; Hobbs, Lew M.; Dahlstrom, Julie

2013-06-01

In the studies of the Diffuse Interstellar Bands (DIBs), the sightline toward Herschel 36 near the center of the HII region Messier 8 is unique. It shows spectra of CH^+ and CH in the first excited level indicating the presence of a cloud with high radiative temperature. The heating is most likely due to far infrared emission from the adjacent intense infrared source Her 36 SE at a distance of 0.25" from Her 36. The effect of the high radiative temperature on some DIBs is spectacular. It produces on a normally symmetric bell-shape line a very prominent Extended Tail toward Red (ETR) on prototypical DIBs λ 5780.5, λ 5797.1, and λ 6613 while other DIBs λ 5849.8, λ 6196.0, and λ 6379.3 are little affected. We interpret this as indicating that the carriers of the former 3 DIBs that are seriously affected by the radiation are polar molecules and the pronounced ETRs are the result of the decrease of rotational constant B (3 - 5 %) upon electronic excitation. High J rotational levels are pumped radiatively and with the negative (B' - B) produces the ETR. We have developed a model calculation of rotational distribution taking into account of both radiative and collisional processes. In view of the complexity of the problem linear molecules are considered. 7 parameters enter into the calculation but we find the fractional variation of B and the radiative temperature T_r are the most decisive. Although molecules with a general shape is beyond the scope of this work, we conclude that the 3 DIBs which show the pronounced ETRs are due to polar molecules and the requirement of high variation of B indicates that the molecules are not that large perhaps composed of 3-6 heavy atoms. The 3 DIBs that do not show the pronounced ETRs are likely due to non-polar molecules or large polar molecules with small fractional variation of B. Goto, M., Stecklum, B., Linz, H., Feldt, M., Henning, Th., Pascucci, I., and Usuda, T. 2006, ApJ, 649 299. Oka, T., Welty, D. E., Johnson, S., York, D. G., Dahlstrom, J., and Hobbs, L. M. 2013, ApJ, submitted

Self-healing of optical functions by molecular metabolism in a swollen elastomer

NASA Astrophysics Data System (ADS)

Saito, Mitsunori; Nishimura, Tatsuya; Sakiyama, Kohei; Inagaki, Sota

2012-12-01

Optical functions of organic dyes, e.g., fluorescence or photochromism, tend to degrade by light irradiation, which causes a short lifetime of photonic devices. Self-healing of optical functions is attainable by metabolizing bleached molecules with nonirradiated ones. A polydimethylsiloxane elastomer provides a useful matrix for dye molecules, since its flexible structure with nano-sized intermolecular spaces allows dye diffusion from a reservoir to an operation region. Swelling the elastomer with a suitable solvent promotes both dissolution and diffusion of dye molecules. This self-healing function was demonstrated by an experiment in which a photochromic elastomer exhibited improved durability against a repeated coloring-decoloring process.

Diffusion of Small Solute Particles in Viscous Liquids: Cage Diffusion, a Result of Decoupling of Solute-Solvent Dynamics, Leads to Amplification of Solute Diffusion.

PubMed

Acharya, Sayantan; Nandi, Manoj K; Mandal, Arkajit; Sarkar, Sucharita; Bhattacharyya, Sarika Maitra

2015-08-27

We study the diffusion of small solute particles through solvent by keeping the solute-solvent interaction repulsive and varying the solvent properties. The study involves computer simulations, development of a new model to describe diffusion of small solutes in a solvent, and also mode coupling theory (MCT) calculations. In a viscous solvent, a small solute diffuses via coupling to the solvent hydrodynamic modes and also through the transient cages formed by the solvent. The model developed can estimate the independent contributions from these two different channels of diffusion. Although the solute diffusion in all the systems shows an amplification, the degree of it increases with solvent viscosity. The model correctly predicts that when the solvent viscosity is high, the solute primarily diffuses by exploiting the solvent cages. In such a scenario the MCT diffusion performed for a static solvent provides a correct estimation of the cage diffusion.

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

TrackArt: the user friendly interface for single molecule tracking data analysis and simulation applied to complex diffusion in mica supported lipid bilayers.

PubMed

Matysik, Artur; Kraut, Rachel S

2014-05-01

Single molecule tracking (SMT) analysis of fluorescently tagged lipid and protein probes is an attractive alternative to ensemble averaged methods such as fluorescence correlation spectroscopy (FCS) or fluorescence recovery after photobleaching (FRAP) for measuring diffusion in artificial and plasma membranes. The meaningful estimation of diffusion coefficients and their errors is however not straightforward, and is heavily dependent on sample type, acquisition method, and equipment used. Many approaches require advanced computing and programming skills for their implementation. Here we present TrackArt software, an accessible graphic interface for simulation and complex analysis of multiple particle paths. Imported trajectories can be filtered to eliminate spurious or corrupted tracks, and are then analyzed using several previously described methodologies, to yield single or multiple diffusion coefficients, their population fractions, and estimated errors. We use TrackArt to analyze the single-molecule diffusion behavior of a sphingolipid analog SM-Atto647N, in mica supported DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) bilayers. Fitting with a two-component diffusion model confirms the existence of two separate populations of diffusing particles in these bilayers on mica. As a demonstration of the TrackArt workflow, we characterize and discuss the effective activation energies required to increase the diffusion rates of these populations, obtained from Arrhenius plots of temperature-dependent diffusion. Finally, TrackArt provides a simulation module, allowing the user to generate models with multiple particle trajectories, diffusing with different characteristics. Maps of domains, acting as impermeable or permeable obstacles for particles diffusing with given rate constants and diffusion coefficients, can be simulated or imported from an image. Importantly, this allows one to use simulated data with a known diffusion behavior as a comparison for results acquired using particular algorithms on actual, "natural" samples whose diffusion behavior is to be extracted. It can also serve as a tool for demonstrating diffusion principles. TrackArt is an open source, platform-independent, Matlab-based graphical user interface, and is easy to use even for those unfamiliar with the Matlab programming environment. TrackArt can be used for accurate simulation and analysis of complex diffusion data, such as diffusion in lipid bilayers, providing publication-quality formatted results.

Demonstrating the feasibility of monitoring the molecular-level structures of moving polymer/silane interfaces during silane diffusion using SFG.

PubMed

Chen, Chunyan; Wang, Jie; Loch, Cheryl L; Ahn, Dongchan; Chen, Zhan

2004-02-04

In this paper, the feasibility of monitoring molecular structures at a moving polymer/liquid interface by sum frequency generation (SFG) vibrational spectroscopy has been demonstrated. N-(2-Aminoethyl)-3-aminopropyltrimethoxysilane (AATM, NH2(CH2)2NH(CH2)3Si(OCH3)3) has been brought into contact with a deuterated poly(methyl methacrylate) (d-PMMA) film, and the interfacial silane structure has been monitored using SFG. Upon initial contact, the SFG spectra can be detected, but as time progresses, the spectral intensity changes and finally disappears. Additional experiments indicate that these silane molecules can diffuse into the polymer film and the detected SFG signals are actually from the moving polymer/silane interface. Our results show that the molecular order of the polymer/silane interface exists during the entire diffusion process and is lost when the silane molecules traverse through the thickness of the d-PMMA film. The loss of the SFG signal is due to the formation of a new disordered substrate/silane interface, which contributes no detectable SFG signal. The kinetics of the diffusion of the silane into the polymer have been deduced from the time-dependent SFG signals detected from the AATM molecules as they diffuse through polymer films of different thickness.

Proline induced disruption of the structure and dynamics of water.

PubMed

Yu, Dehong; Hennig, Marcus; Mole, Richard A; Li, Ji Chen; Wheeler, Cheryl; Strässle, Thierry; Kearley, Gordon J

2013-12-21

We use quasi-elastic neutron scattering spectroscopy to study the diffusive motion of water molecules at ambient temperature as a function of the solute molar fraction of the amino acid, proline. We validate molecular dynamics simulations against experimental quasielastic neutron scattering data and then use the simulations to reveal, and understand, a strong dependence of the translational self-diffusion coefficient of water on the distance to the amino acid molecule. An analysis based on the juxtaposition of water molecules in the simulation shows that the rigidity of proline imposes itself on the local water structure, which disrupts the hydrogen-bond network of water leading to an increase in the mean lifetime of hydrogen bonds. The net effect is some distortion of the proline molecule and a slowing down of the water mobility.

Molecular Dynamics Study of the Solution Structure, Clustering, and Diffusion of Four Aqueous Alkanolamines.

PubMed

Melnikov, Sergey M; Stein, Matthias

2018-03-15

CO 2 sequestration from anthropogenic resources is a challenge to the design of environmental processes at a large scale. Reversible chemical absorption by amine-based solvents is one of the most efficient methods of CO 2 removal. Molecular simulation techniques are very useful tools to investigate CO 2 binding by aqueous alkanolamine molecules for further technological application. In the present work, we have performed detailed atomistic molecular dynamics simulations of aqueous solutions of three prototype amines: monoethanolamine (MEA) as a standard, 3-aminopropanol (MPA), 2-methylaminoethanol (MMEA), and 4-diethylamino-2-butanol (DEAB) as potential novel CO 2 absorptive solvents. Solvent densities, radial distribution functions, cluster size distributions, hydrogen-bonding statistics, and diffusion coefficients for a full range of mixture compositions have been obtained. The solvent densities and diffusion coefficients from simulations are in good agreement with those in the experiment. In aqueous solution, MEA, MPA, and MMEA molecules prefer to be fully solvated by water molecules, whereas DEAB molecules tend to self-aggregate. In a range from 30/70-50/50 (w/w) alkanolamine/water mixtures, they form a bicontinuous phase (both alkanolamine and water are organized in two mutually percolating clusters). Among the studied aqueous alkanolamine solutions, the diffusion coefficients decrease in the following order MEA > MPA = MMEA > DEAB. With an increase of water content, the diffusion coefficients increase for all studied alkanolamines. The presented results are a first step for process-scale simulation and provide important qualitative and quantitative information for the design and engineering of efficient new CO 2 removal processes.

Rapid Water Transport through Organic Layers on Ice.

PubMed

Kong, Xiangrui; Toubin, Céline; Habartova, Alena; Pluharova, Eva; Roeselova, Martina; Pettersson, Jan B C

2018-05-31

Processes involving atmospheric aerosol and cloud particles are affected by condensation of organic compounds that are omnipresent in the atmosphere. On ice particles, organic compounds with hydrophilic functional groups form hydrogen bonds with the ice and orient their hydrophobic groups away from the surface. The organic layer has been expected to constitute a barrier to gas uptake, but recent experimental studies suggest that the accommodation of water molecules on ice is only weakly affected by condensed short-chain alcohol layers. Here, we employ molecular dynamics simulations to study the water interactions with n-butanol covered ice at 200 K and show that the small effect of the condensed layer is due to efficient diffusion of water molecules along the surface plane while seeking appropriate sites to penetrate, followed by penetration driven by the combined attractive forces from butanol OH groups and water molecules within the ice. The water molecules that penetrate through the n-butanol layer become strongly bonded by approximately three hydrogen bonds at the butanol-ice interface. The obtained accommodation coefficient (0.81 ± 0.03) is in excellent agreement with results from previous environmental molecular beam experiments, leading to a picture where an adsorbed n-butanol layer does not alter the apparent accommodation coefficient but dramatically changes the detailed molecular dynamics and kinetics.

Noise analysis of antibiotic permeation through bacterial channels

NASA Astrophysics Data System (ADS)

Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.

2003-05-01

Statistical analysis of high-resolution current recordings from a single ion channel reconstituted into a planar lipid membrane allows us to study transport of antibiotics at the molecular detail. Working with the general bacterial porin, OmpF, we demonstrate that addition of zwitterionic β-lactam antibiotics to the membrane-bathing solution introduces transient interruptions in the small-ion current through the channel. Time-resolved measurements reveal that one antibiotic molecule blocks one of the monomers in the OmpF trimer for characteristic times from microseconds to hundreds of microseconds. Spectral noise analysis enables us to perform measurements over a wide range of changing parameters. In all cases studied, the residence time of an antibiotic molecule in the channel exceeds the estimated time for free diffusion by orders of magnitude. This demonstrates that, in analogy to substrate-specific channels that evolved to bind specific metabolite molecules, antibiotics have 'evolved' to be channel-specific. The charge distribution of an efficient antibiotic complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a zone of attraction inside the channel and compensates the penetrating molecule's entropy loss and desolvation energy. This facilitates antibiotic translocation through the narrowest part of the channel and accounts for higher antibiotic permeability rates.

Imaging of conformational changes

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

Michl, Josef

2016-03-13

Control of intramolecular conformational change in a small number of molecules or even a single one by an application of an outside electric field defined by potentials on nearby metal or dielectric surfaces has potential applications in both 3-D and 2-D nanotechnology. Specifically, the synthesis, characterization, and understanding of designed solids with controlled built-in internal rotational motion of a dipole promises a new class of materials with intrinsic dielectric, ferroelectric, optical and optoelectronic properties not found in nature. Controlled rotational motion is of great interest due to its expected utility in phenomena as diverse as transport, current flow in molecularmore » junctions, diffusion in microfluidic channels, and rotary motion in molecular machines. A direct time-resolved observation of the dynamics of motion on ps or ns time scale in a single molecule would be highly interesting but is also very difficult and has yet to be accomplished. Much can be learned from an easier but still challenging comparison of directly observed initial and final orientational states of a single molecule, which is the basis of this project. The project also impacts the understanding of surface-enhanced Raman spectroscopy (SERS) and single-molecule spectroscopic detection, as well as the synthesis of solid-state materials with tailored properties from designed precursors.« less

Centrosymmetric molecules as possible carriers of diffuse interstellar bands

NASA Astrophysics Data System (ADS)

Kaźmierczak, M.; Schmidt, M. R.; Galazutdinov, G. A.; Musaev, F. A.; Betelesky, Y.; Krełowski, J.

2010-11-01

In this paper, we present new data with interstellar C2 (Phillips bands A 1 Πu-X1 Σ+g), from observations made with the Ultraviolet-Visual Echelle Spectrograph of the European Southern Observatory. We have determined the interstellar column densities and excitation temperatures of C2 for nine Galactic lines. For seven of these, C2 has never been observed before, so in this case the still small sample of interstellar clouds (26 lines of sight), where a detailed analysis of C2 excitation has been made, has increased significantly. This paper is a continuation of previous works where interstellar molecules (C2 and diffuse interstellar bands) have been analysed. Because the sample of interstellar clouds with C2 has increased, we can show that the width and shape of the profiles of some diffuse interstellar bands (6196 and 5797 Å) apparently depend on the gas kinetic and rotational temperatures of C2; the profiles are broader because of the higher values of the gas kinetic and rotational temperatures of C2. There are also diffuse interstellar bands (4964 and 5850 Å) for which this effect does not exist. Based on observations made with ESO telescopes at the Paranal Observatory under programme IDs 266.D-5655(A), 67.C-0281(A), 71.C-0513(C), 67.D-0439(A) and 082.C-0566(A) and at La Silla under programme IDs 078.C-0403(A), 076.C-0164(A) and 073.C-0337(A). Also based on observations made with the 1.8-m telescope in South Korea and the 2-m telescope at the International Centre for Astronomical and Medico-Ecological Research, Terskol, Russia. E-mail: kazmierczak@astri.uni.torun.pl (MK); schmidt@ncac.torun.pl (MRS); runizag@gmail.com (GAG); ybialets@eso.org (YB); jacek@astri.uni.torun.pl (JK)

Single molecule studies of solvent-dependent diffusion and entrapment in poly(dimethylsiloxane) thin films.

PubMed

Lange, Jeffrey J; Culbertson, Christopher T; Higgins, Daniel A

2008-12-15

Single molecule microscopic and spectroscopic methods are employed to probe the mobility and physical entrapment of dye molecules in dry and solvent-loaded poly(dimethylsiloxane) (PDMS) films. PDMS films of approximately 220 nm thickness are prepared by spin casting dilute solutions of Sylgard 184 onto glass coverslips, followed by low temperature curing. A perylene diimide dye (BPPDI) is used to probe diffusion and molecule-matrix interactions. Two classes of dye-loaded samples are investigated: (i) those incorporating dye dispersed throughout the films ("in film" samples) and (ii) those in which the dye is restricted primarily to the PDMS surface ("on film" samples). Experiments are performed under dry nitrogen and at various levels of isopropyl alcohol (IPA) loading from the vapor phase. A PDMS-coated quartz-crystal microbalance is employed to monitor solvent loading and drying of the PDMS and to ensure equilibrium conditions are achieved. Single molecules are shown to be predominantly immobile under dry conditions and mostly mobile under IPA-saturated conditions. Quantitative methods for counting the fluorescent spots produced by immobile single molecules in optical images of the samples demonstrate that the population of mobile molecules increases nonlinearly with IPA loading. Even under IPA saturated conditions, the population of fixed molecules is found to be greater than zero and is greatest for "in film" samples. Fluorescence correlation spectroscopy is used to measure the apparent diffusion coefficient for the mobile molecules, yielding a mean value of D = 1.4(+/-0.4) x 10(-8) cm(2)/s that is virtually independent of IPA loading and sample class. It is concluded that a nonzero population of dye molecules is physically entrapped within the PDMS matrix under all conditions. The increase in the population of mobile molecules under high IPA conditions is attributed to the filling of film micropores with solvent, rather than by incorporation of molecularly dispersed solvent into the PDMS.

Single-Molecule Optical Spectroscopy and Imaging: From Early Steps to Recent Advances

NASA Astrophysics Data System (ADS)

Moerner, William E.

The initial steps toward optical detection and spectroscopy of single molecules arose out of the study of spectral hole-burning in inhomogeneously broadened optical absorption profiles of molecular impurities in solids at low temperatures. Spectral signatures relating to the fluctuations of the number of molecules in resonance led to the attainment of the single-molecule limit in 1989. In the early 1990s, many fascinating physical effects were observed for individual molecules such as spectral diffusion, optical switching, vibrational spectra, and magnetic resonance of a single molecular spin. Since the mid-1990s when experiments moved to room temperature, a wide variety of biophysical effects may be explored, and a number of physical phenomena from the low temperature studies have analogs at high temperature. Recent advances worldwide cover a huge range, from in vitro studies of enzymes, proteins, and oligonucleotides, to observations in real time of a single protein performing a specific function inside a living cell. Because each single fluorophore acts a light source roughly 1 nm in size, microscopic observation of individual fluorophores leads naturally to localization beyond the optical diffraction limit. Combining this with active optical control of the number of emitting molecules leads to superresolution imaging, a new frontier for optical microscopy beyond the optical diffraction limit and for chemical design of photoswitchable fluorescent labels. Finally, to study one molecule in aqueous solution without surface perturbations, a new electrokinetic trap is described (the ABEL trap) which can trap single small biomolecules without the need for large dielectric beads.

Stochastic Physicochemical Dynamics

NASA Astrophysics Data System (ADS)

Tsekov, R.

2001-02-01

Thermodynamic Relaxation in Quantum Systems: A new approach to quantum Markov processes is developed and the corresponding Fokker-Planck equation is derived. The latter is examined to reproduce known results from classical and quantum physics. It was also applied to the phase-space description of a mechanical system thus leading to a new treatment of this problem different from the Wigner presentation. The equilibrium probability density obtained in the mixed coordinate-momentum space is a reasonable extension of the Gibbs canonical distribution. The validity of the Einstein fluctuation-dissipation relation is discussed in respect to the type of relaxation in an isothermal system. The first model, presuming isothermic fluctuations, leads to the Einstein formula. The second model supposes adiabatic fluctuations and yields another relation between the diffusion coefficient and mobility of a Brownian particle. A new approach to relaxations in quantum systems is also proposed that demonstrates applicability only of the adiabatic model for description of the quantum Brownian dynamics. Stochastic Dynamics of Gas Molecules: A stochastic Langevin equation is derived, describing the thermal motion of a molecule immersed in a rested fluid of identical molecules. The fluctuation-dissipation theorem is proved and a number of correlation characteristics of the molecular Brownian motion are obtained. A short review of the classical theory of Brownian motion is presented. A new method is proposed for derivation of the Fokker-Planck equations, describing the probability density evolution, from stochastic differential equations. It is also proven via the central limit theorem that the white noise is only Gaussian. The applicability of stochastic differential equations to thermodynamics is considered and a new form, different from the classical Ito and Stratonovich forms, is introduced. It is shown that the new presentation is more appropriate for the description of thermodynamic fluctuations. The range of validity of the Boltzmann-Einstein principle is also discussed and a generalized alternative is proposed. Both expressions coincide in the small fluctuation limit, providing a normal distribution density. Fluctuation Stability of Thin Liquid Films: Memory effect of Brownian motion in an incompressible fluid is studied. The reasoning is based on the Mori-Zwanzig formalism and a new formulation of the Langevin force as a result of collisions between an effective and the Brownian particles. Thus, the stochastic force autocorrelation function with finite dispersion and the corresponding Brownian particle velocity autocorrelation function are obtained. It is demonstrated that the dynamic structure is very important for the rate of drainage of a thin liquid film and it can be effectively taken into account by a dynamic fractal dimension. It is shown that the latter is a powerful tool for description of the film drainage and classifies all the known results from the literature. The obtained general expression for the thinning rate is a heuristic one and predicts variety of drainage models, which are even difficult to simulate in practice. It is a typical example of a scaling law, which explains the origin of the complicate dependence of the thinning rate on the film radius. On the basis of the theory of stochastic processes the evolution of the spatial correlation function of the surface waves on a thin liquid film as well as the corresponding root mean square amplitude A(t) and number of uncorrelated subdomains N(t) are obtained. A formulation of the life time of unstable nonthinning films is proposed, based on the evolution of A and N. It is shown that the presence of uncorrelated subdomains shortens the life time of the film. Some numerical results for A(t) and N(t) at different film thicknesses h and areas S, are demonstrated, taking into account only van der Waals and capillary forces. Resonant Diffusion in Molecular Solid Structures: A new approach to Brownian motion of atomic clusters on solid surfaces is developed. The main topic discussed is the dependence of the diffusion coefficient on the fit between the surface static potential and the internal cluster configuration. It is shown this dependence is non-monotonous, which is the essence of the so-called resonant diffusion. Assuming quicker inner motion of the cluster than its translation, adiabatic separation of these variables is possible and a relatively simple expression for the diffusion coefficient is obtained. In this way, the role of cluster vibrations is accounted for, thus leading to a more complex resonance in the cluster surface mobility. Diffusion of normal alkanes in one-dimensional zeolites is theoretically studied on the basis of the stochastic equation formalism. The calculated diffusion coefficient accounts for the vibrations of the diffusing molecule and zeolite framework, molecule-zeolite interaction, and specific structure of the zeolite. It is shown that when the interaction potential is predominantly determined by the zeolite pore structure, the diffusion coefficient varies periodically with the number of carbon atoms of the alkane molecule, a phenomenon called resonant diffusion. A criterion for observable resonance is obtained from the balance between the interaction potentials of the molecule due to the atomic and pore structures of the zeolite. It shows that the diffusion is not resonant in zeolites without pore structure, such as ZSM-12. Moreover, even in zeolites with developed pore structure no resonant dependence of the diffusion constant can be detected if the pore structure energy barriers are not at least three times higher than the atomic structure energy barriers. The role of the alkane molecule vibrations is examined as well and a surprising effect of suppression of the diffusion in comparison with the case of a rigid molecule is observed. This effect is explained with the balance between the static and dynamic interaction of the molecule and zeolite. Catalytic Kinetics of Chemical Dissociation: A unified description of the catalytic effect of Cu-exchanged zeolites is proposed for the decomposition of NO. A general expression for the rate constant of NO decomposition is obtained by assuming that the rate-determining step consists of the transferring of a single atom associated with breaking of the N-O bond. The analysis is performed on the base of the generalized Langevin equation and takes into account both the potential interactions in the system and the memory effects due to the zeolite vibrations. Two different mechanisms corresponding to monomolecular and bimolecular NO decomposition are discussed. The catalytic effect in the monomolecular mechanism is related to both the Cu+ ions and zeolite O-vacancies, while in the case of the bimolecular mechanism the zeolite contributes through dissipation only. The comparison of the theoretically calculated rate constants with experimental results reveals additional information about the geometric and energetic characteristics of the active centers and confirms the logic of the proposed models.

Lenalidomide And Rituximab as Maintenance Therapy in Treating Patients With B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2015-11-25

Adult Non-Hodgkin Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

Atomistic Simulation Studies of Cholesteryl Oleates: Model for the Core of Lipoprotein Particles

PubMed Central

Heikelä, Mikko; Vattulainen, Ilpo; Hyvönen, Marja T.

2006-01-01

We have conducted molecular dynamics simulations to gain insight into the atomic-scale properties of an isotropic system of cholesteryl oleate (CO) molecules. Cholesteryl esters are major constituents of low density lipoprotein particles, the key players in the formation of atherosclerosis, as well as the storage form of cholesterol. Here the aim is to clarify structural and dynamical properties of CO molecules under conditions, which are suggestive of those in the core of low density lipoprotein particles. The simulations in the fluid phase indicate that the system of CO molecules is characterized by an absence of translational order, as expected, while the orientational order between distinct CO molecules is significant at short distances, persisting over a molecular size. As for intramolecular properties, the bonds along the oleate chain are observed to be weakly ordered with respect to the sterol structure, unlike the bonds along the short hydrocarbon chain of cholesterol where the ordering is significant. The orientational distribution of the oleate chain as a whole with respect to the sterol moiety is of broad nature, having a major amount of extended and a less considerable proportion of bended structures. Distinct transient peaks at specific angles also appear. The diffusion of CO molecules is found to be a slow process and characterized by a diffusion coefficient of the order of 2 × 10−9 cm2/s. This is considerably slower than diffusion, e.g., in ordered domains of lipid membranes rich in sphingomyelin and cholesterol. Analysis of the rotational diffusion rates and trans-to-gauche transition rates yield results consistent with experiments. PMID:16399839

Molecular dynamics simulation of solute diffusion in Lennard-Jones fluids

NASA Astrophysics Data System (ADS)

Yamaguchi, T.; Kimura, Y.; Hirota, N.

We performed a molecular dynamics (MD) simulation for a system of 5 solute molecules in 495 solvent molecules interacting through the Lennard-Jones (LJ) 12-6 potential, in order to study solvent density effects on the diffusion coefficients in supercritical fluids. The effects of the size of the solute and the strength of the solute-solvent attractive interaction on the diffusion coefficient of the solute were examined. The diffusion coefficients of the solute molecules were calculated at T = 1.5 (in the LJ reduced unit), slightly above the critical temperature, from rho = 0.1 to rho = 0.95, where rho is the number density in the LJ reduced unit. The memory function in the generalized Langevin equation was calculated, in order to know the molecular origin of the friction on a solute. The memory function is separated into fast and slow components. The former arises from the solute-solvent repulsive interaction, and is interpreted as collisional Enskog-like friction. The interaction strength dependence of the collisional friction is larger in the low- and medium-density regions, which is consistent with the 'clustering' picture, i.e., the local density enhancement due to the solute-solvent attractive interaction. However, the slow component of the memory function suppresses the effect of the local density on the diffusion coefficients, and as a result the effect of the attractive interaction is smaller on the diffusion coefficients than on the local density. Nonetheless, the solvent density dependence of the effect of the attraction on the diffusion coefficient varies with the local density, and it is concluded that the local density is the principal factor that determines the interaction strength dependence of the diffusion coefficient in the low- and medium-density regions (p < 0.6).

Quantum dynamics of small H2 and D2 clusters in the large cage of structure II clathrate hydrate: Energetics, occupancy, and vibrationally averaged cluster structures

NASA Astrophysics Data System (ADS)

Sebastianelli, Francesco; Xu, Minzhong; Bačić, Zlatko

2008-12-01

We report diffusion Monte Carlo (DMC) calculations of the quantum translation-rotation (T-R) dynamics of one to five para-H2 (p-H2) and ortho-D2 (o-D2) molecules inside the large hexakaidecahedral (51264) cage of the structure II clathrate hydrate, which was taken to be rigid. These calculations provide a quantitative description of the size evolution of the ground-state properties, energetics, and the vibrationally averaged geometries, of small (p-H2)n and (o-D2)n clusters, n=1-5, in nanoconfinement. The zero-point energy (ZPE) of the T-R motions rises steeply with the cluster size, reaching 74% of the potential well depth for the caged (p-H2)4. At low temperatures, the rapid increase of the cluster ZPE as a function of n is the main factor that limits the occupancy of the large cage to at most four H2 or D2 molecules, in agreement with experiments. Our DMC results concerning the vibrationally averaged spatial distribution of four D2 molecules, their mean distance from the cage center, the D2-D2 separation, and the specific orientation and localization of the tetrahedral (D2)4 cluster relative to the framework of the large cage, agree very well with the low-temperature neutron diffraction experiments involving the large cage with the quadruple D2 occupancy.

Quantum dynamics of small H2 and D2 clusters in the large cage of structure II clathrate hydrate: energetics, occupancy, and vibrationally averaged cluster structures.

PubMed

Sebastianelli, Francesco; Xu, Minzhong; Bacić, Zlatko

2008-12-28

We report diffusion Monte Carlo (DMC) calculations of the quantum translation-rotation (T-R) dynamics of one to five para-H(2) (p-H(2)) and ortho-D(2) (o-D(2)) molecules inside the large hexakaidecahedral (5(12)6(4)) cage of the structure II clathrate hydrate, which was taken to be rigid. These calculations provide a quantitative description of the size evolution of the ground-state properties, energetics, and the vibrationally averaged geometries, of small (p-H(2))(n) and (o-D(2))(n) clusters, n=1-5, in nanoconfinement. The zero-point energy (ZPE) of the T-R motions rises steeply with the cluster size, reaching 74% of the potential well depth for the caged (p-H(2))(4). At low temperatures, the rapid increase of the cluster ZPE as a function of n is the main factor that limits the occupancy of the large cage to at most four H(2) or D(2) molecules, in agreement with experiments. Our DMC results concerning the vibrationally averaged spatial distribution of four D(2) molecules, their mean distance from the cage center, the D(2)-D(2) separation, and the specific orientation and localization of the tetrahedral (D(2))(4) cluster relative to the framework of the large cage, agree very well with the low-temperature neutron diffraction experiments involving the large cage with the quadruple D(2) occupancy.

Feedback traps for virtual potentials

NASA Astrophysics Data System (ADS)

Gavrilov, Momčilo; Bechhoefer, John

2017-03-01

Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other single-molecule techniques, they use feedback to counteract the Brownian motion of a molecule of interest. The trap first acquires information about a molecule's position and then applies an electric feedback force to move the molecule. Since electric forces are stronger than optical forces at small scales, feedback traps are the best way to trap single molecules without `touching' them (e.g. by putting them in a small box or attaching them to a tether). Feedback traps can do more than trap molecules: they can also subject a target object to forces that are calculated to be the gradient of a desired potential function U(x). If the feedback loop is fast enough, it creates a virtual potential whose dynamics will be very close to those of a particle in an actual potential U(x). But because the dynamics are entirely a result of the feedback loop-absent the feedback, there is only an object diffusing in a fluid-we are free to specify and then manipulate in time an arbitrary potential U(x,t). Here, we review recent applications of feedback traps to studies on the fundamental connections between information and thermodynamics, a topic where feedback plays an even more fundamental role. We discuss how recursive maximum-likelihood techniques allow continuous calibration, to compensate for drifts in experiments that last for days. We consider ways to estimate work and heat, using them to measure fluctuating energies to a precision of ±0.03 kT over these long experiments. Finally, we compare work and heat measurements of the costs of information erasure, the Landauer limit of kT ln 2 per bit of information erased. We argue that, when you want to know the average heat transferred to a bath in a long protocol, you should measure instead the average work and then infer the heat using the first law of thermodynamics. This article is part of the themed issue 'Horizons of cybernetical physics'.

The diffusion of ions in unconsolidated sediments

USGS Publications Warehouse

Manheim, F.T.

1970-01-01

Diffusion in unconsolidated sediments generally proceeds at rates ranging from half to one twentieth of those applying to diffusion of ions and molecules in free solution. Diffusion rates are predictable with respect to porosity and path tortuosity in host sediments, and can be conveniently measured by determinations of electrical resistivity on bulk sediment samples. Net ion flux is further influenced by reactions of diffusing species with enclosing sediments, but such influences should not be confused with or lumped with diffusion processes. ?? 1970.

Developments in the Implementation of Acoustic Droplet Ejection for Protein Crystallography.

PubMed

Wu, Ping; Noland, Cameron; Ultsch, Mark; Edwards, Bonnie; Harris, David; Mayer, Robert; Harris, Seth F

2016-02-01

Acoustic droplet ejection (ADE) enables crystallization experiments at the low-nanoliter scale, resulting in rapid vapor diffusion equilibration dynamics and efficient reagent usage in the empirical discovery of structure-enabling protein crystallization conditions. We extend our validation of this technology applied to the diverse physicochemical property space of aqueous crystallization reagents where dynamic fluid analysis coupled to ADE aids in accurate and precise dispensations. Addition of crystallization seed stocks, chemical additives, or small-molecule ligands effectively modulates crystallization, and we here provide examples in optimization of crystal morphology and diffraction quality by the acoustic delivery of ultra-small volumes of these cofactors. Additional applications are discussed, including set up of in situ proteolysis and alternate geometries of crystallization that leverage the small scale afforded by acoustic delivery. Finally, we describe parameters of a system of automation in which the acoustic liquid handler is integrated with a robotic arm, plate centrifuge, peeler, sealer, and stacks, which allows unattended high-throughput crystallization experimentation. © 2015 Society for Laboratory Automation and Screening.

Interspecies scaling and prediction of human clearance: comparison of small- and macro-molecule drugs

PubMed Central

Huh, Yeamin; Smith, David E.; Feng, Meihau Rose

2014-01-01

Human clearance prediction for small- and macro-molecule drugs was evaluated and compared using various scaling methods and statistical analysis.Human clearance is generally well predicted using single or multiple species simple allometry for macro- and small-molecule drugs excreted renally.The prediction error is higher for hepatically eliminated small-molecules using single or multiple species simple allometry scaling, and it appears that the prediction error is mainly associated with drugs with low hepatic extraction ratio (Eh). The error in human clearance prediction for hepatically eliminated small-molecules was reduced using scaling methods with a correction of maximum life span (MLP) or brain weight (BRW).Human clearance of both small- and macro-molecule drugs is well predicted using the monkey liver blood flow method. Predictions using liver blood flow from other species did not work as well, especially for the small-molecule drugs. PMID:21892879

Using the QCM Biosensor-Based T7 Phage Display Combined with Bioinformatics Analysis for Target Identification of Bioactive Small Molecule.

PubMed

Takakusagi, Yoichi; Takakusagi, Kaori; Sugawara, Fumio; Sakaguchi, Kengo

2018-01-01

Identification of target proteins that directly bind to bioactive small molecule is of great interest in terms of clarifying the mode of action of the small molecule as well as elucidating the biological phenomena at the molecular level. Of the experimental technologies available, T7 phage display allows comprehensive screening of small molecule-recognizing amino acid sequence from the peptide libraries displayed on the T7 phage capsid. Here, we describe the T7 phage display strategy that is combined with quartz-crystal microbalance (QCM) biosensor for affinity selection platform and bioinformatics analysis for small molecule-recognizing short peptides. This method dramatically enhances efficacy and throughput of the screening for small molecule-recognizing amino acid sequences without repeated rounds of selection. Subsequent execution of bioinformatics programs allows combinatorial and comprehensive target protein discovery of small molecules with its binding site, regardless of protein sample insolubility, instability, or inaccessibility of the fixed small molecules to internally located binding site on larger target proteins when conventional proteomics approaches are used.

Evolution and Transport of Water in the Upper Regolith of Mars

NASA Technical Reports Server (NTRS)

Hudson, T. L.; Aharonson, O.; Schorghofer, N.; Hecht, M. H.; Bridges, N. T.; Green, J. R.

2003-01-01

Long standing theoretical predictions [1-3], as well as recent spacecraft observations [4] indicate that large quantities of ice is present in the high latitudes upper decimeters to meters of the Martian regolith. At shallower depths and warmer locations small amounts of H2O, either adsorbed or free, may be present transiently. An understanding of the evolution of water based on theoretical and experimental considerations of the processes operating at the Martian environment is required. In particular, the porosity, diffusivity, and permeability of soils and their effect on water vapor transport under Mars-like conditions have been estimated, but experimental validation of such models is lacking. Goal: Three related mechanisms may affect water transport in the upper Martian regolith. 1) diffusion along a concentration gradient under isobaric conditions, 2) diffusion along a thermal gradient, which may give rise to a concentration gradient as ice sublimes or molecules desorb from the regolith, and 3) hydraulic flow, or mass motion in response to a pressure gradient. Our combined theoretical and experimental investigation seeks to disentangle these mechanisms and determine which process(es) are dominant in the upper regolith over various timescales. A detailed one-dimensional model of the upper regolith is being created which incorporates water adsorption/ desorption, condensation, porosity, diffusivity, and permeability effects. Certain factors such as diffusivity are difficult to determine theoretically due to the wide range of intrinsic grain properties such as particle sizes, shapes, packing densities, and emergent properties such as tortuosity. An experiment is being designed which will allow us to more accurately determine diffusivity, permeability, and water desorption isotherms for regolith simulants.

Equation-of-motion coupled-cluster method for doubly ionized states with spin-orbit coupling.

PubMed

Wang, Zhifan; Hu, Shu; Wang, Fan; Guo, Jingwei

2015-04-14

In this work, we report implementation of the equation-of-motion coupled-cluster method for doubly ionized states (EOM-DIP-CC) with spin-orbit coupling (SOC) using a closed-shell reference. Double ionization potentials (DIPs) are calculated in the space spanned by 2h and 3h1p determinants with the EOM-DIP-CC approach at the CC singles and doubles level (CCSD). Time-reversal symmetry together with spatial symmetry is exploited to reduce computational effort. To circumvent the problem of unstable dianion references when diffuse basis functions are included, nuclear charges are scaled. Effect of this stabilization potential on DIPs is estimated based on results from calculations using a small basis set without diffuse basis functions. DIPs and excitation energies of some low-lying states for a series of open-shell atoms and molecules containing heavy elements with two unpaired electrons have been calculated with the EOM-DIP-CCSD approach. Results show that this approach is able to afford a reliable description on SOC splitting. Furthermore, the EOM-DIP-CCSD approach is shown to provide reasonable excitation energies for systems with a dianion reference when diffuse basis functions are not employed.

Equation-of-motion coupled-cluster method for doubly ionized states with spin-orbit coupling

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

Wang, Zhifan; Hu, Shu; Guo, Jingwei

2015-04-14

In this work, we report implementation of the equation-of-motion coupled-cluster method for doubly ionized states (EOM-DIP-CC) with spin-orbit coupling (SOC) using a closed-shell reference. Double ionization potentials (DIPs) are calculated in the space spanned by 2h and 3h1p determinants with the EOM-DIP-CC approach at the CC singles and doubles level (CCSD). Time-reversal symmetry together with spatial symmetry is exploited to reduce computational effort. To circumvent the problem of unstable dianion references when diffuse basis functions are included, nuclear charges are scaled. Effect of this stabilization potential on DIPs is estimated based on results from calculations using a small basis setmore » without diffuse basis functions. DIPs and excitation energies of some low-lying states for a series of open-shell atoms and molecules containing heavy elements with two unpaired electrons have been calculated with the EOM-DIP-CCSD approach. Results show that this approach is able to afford a reliable description on SOC splitting. Furthermore, the EOM-DIP-CCSD approach is shown to provide reasonable excitation energies for systems with a dianion reference when diffuse basis functions are not employed.« less

Using nonlinear ac electrokinetics vortex flow to enhance catalytic activities of sol-gel encapsulated trypsin in microfluidic devices

PubMed Central

Wang, Shau-Chun; Chen, Hsiao-Ping; Lai, Yi-Wen; Chau, Lai-Kwan; Chuang, Yu-Chun; Chen, Yi-Jie

2007-01-01

A novel microstirring strategy is applied to accelerate the digestion rate of the substrate Nα-benzoyl-L-arginine-4-nitroanilide (L-BAPA) catalyzed by sol-gel encapsulated trypsin. We use an ac nonlinear electrokinetic vortex flow to stir the solution in a microfluidic reaction chamber to reduce the diffusion length between the immobilized enzyme and substrate in the solution. High-intensity nonlinear electroosmotic microvortices, with angular speeds in excess of 1 cm∕s, are generated around a small (∼1.2 mm) conductive ion exchange granule when ac electric fields (133 V∕cm) are applied across a miniature chamber smaller than 10 μl. Coupling between these microvortices and the on-and-off electrophoretic motion of the granule in low frequency (0.1 Hz) ac fields produces chaotic stream lines to stir substrate molecules sufficiently. We demonstrate that, within a 5-min digestion period, the catalytic reaction rate of immobilized trypsin increases almost 30-fold with adequate reproducibility (15%) due to sufficient stirring action through the introduction of the nonlinear electrokinetic vortices. In contrast, low-frequency ac electroosmotic flow without the granule, provides limited stirring action and increases the reaction rate approximately ninefold with barely acceptable reproducibility (30%). Dye molecules are used to characterize the increases in solute diffusivity in the reaction reservoir in which sol-gel particles are placed, with and without the presence of granule, and compared with the static case. The solute diffusivity enhancement data show respective increases of ∼30 and ∼8 times, with and without the presence of granule. These numbers are consistent with the ratios of the enhanced reaction rate. PMID:19693360

Using nonlinear ac electrokinetics vortex flow to enhance catalytic activities of sol-gel encapsulated trypsin in microfluidic devices.

PubMed

Wang, Shau-Chun; Chen, Hsiao-Ping; Lai, Yi-Wen; Chau, Lai-Kwan; Chuang, Yu-Chun; Chen, Yi-Jie

2007-09-04

A novel microstirring strategy is applied to accelerate the digestion rate of the substrate N(alpha)-benzoyl-L-arginine-4-nitroanilide (L-BAPA) catalyzed by sol-gel encapsulated trypsin. We use an ac nonlinear electrokinetic vortex flow to stir the solution in a microfluidic reaction chamber to reduce the diffusion length between the immobilized enzyme and substrate in the solution. High-intensity nonlinear electroosmotic microvortices, with angular speeds in excess of 1 cms, are generated around a small ( approximately 1.2 mm) conductive ion exchange granule when ac electric fields (133 Vcm) are applied across a miniature chamber smaller than 10 mul. Coupling between these microvortices and the on-and-off electrophoretic motion of the granule in low frequency (0.1 Hz) ac fields produces chaotic stream lines to stir substrate molecules sufficiently. We demonstrate that, within a 5-min digestion period, the catalytic reaction rate of immobilized trypsin increases almost 30-fold with adequate reproducibility (15%) due to sufficient stirring action through the introduction of the nonlinear electrokinetic vortices. In contrast, low-frequency ac electroosmotic flow without the granule, provides limited stirring action and increases the reaction rate approximately ninefold with barely acceptable reproducibility (30%). Dye molecules are used to characterize the increases in solute diffusivity in the reaction reservoir in which sol-gel particles are placed, with and without the presence of granule, and compared with the static case. The solute diffusivity enhancement data show respective increases of approximately 30 and approximately 8 times, with and without the presence of granule. These numbers are consistent with the ratios of the enhanced reaction rate.

Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

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

J Torin Huzil; S Sivaloganathan; M Kohandel

The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein andmore » nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.« less

Facilities for small-molecule crystallography at synchrotron sources.

PubMed

Barnett, Sarah A; Nowell, Harriott; Warren, Mark R; Wilcox, Andrian; Allan, David R

2016-01-01

Although macromolecular crystallography is a widely supported technique at synchrotron radiation facilities throughout the world, there are, in comparison, only very few beamlines dedicated to small-molecule crystallography. This limited provision is despite the increasing demand for beamtime from the chemical crystallography community and the ever greater overlap between systems that can be classed as either small macromolecules or large small molecules. In this article, a very brief overview of beamlines that support small-molecule single-crystal diffraction techniques will be given along with a more detailed description of beamline I19, a dedicated facility for small-molecule crystallography at Diamond Light Source.

Simulation of single-molecule trapping in a nanochannel

PubMed Central

Robinson, William Neil; Davis, Lloyd M.

2010-01-01

The detection and trapping of single fluorescent molecules in solution within a nanochannel is studied using numerical simulations. As optical forces are insufficient for trapping molecules much smaller than the optical wavelength, a means for sensing a molecule’s position along the nanochannel and adjusting electrokinetic motion to compensate diffusion is assessed. Fluorescence excitation is provided by two adjacently focused laser beams containing temporally interleaved laser pulses. Photon detection is time-gated, and the displacement of the molecule from the middle of the two foci alters the count rates collected in the two detection channels. An algorithm for feedback control of the electrokinetic motion in response to the timing of photons, to reposition the molecule back toward the middle for trapping and to rapidly reload the trap after a molecule photobleaches or escapes, is evaluated. While accommodating the limited electrokinetic speed and the finite latency of feedback imposed by experimental hardware, the algorithm is shown to be effective for trapping fast-diffusing single-chromophore molecules within a micron-sized confocal region. Studies show that there is an optimum laser power for which loss of molecules from the trap due to either photobleaching or shot-noise fluctuations is minimized. PMID:20799801

Diffusivity of dicarboxylic acids molecules to secondary organic material governed by particle phase state

NASA Astrophysics Data System (ADS)

Han, Y.; Gong, Z.; Liu, P.; de Sá, S. S.; McKinney, K. A.; Martin, S. T.

2017-12-01

Atmospheric secondary organic material (SOM) from oxidation of volatile organic compounds can exist in amorphous solid, semisolid, and liquid states depending on a range of factors such as relative humidity (RH), temperature, and reaction history. The phase state of SOM affects the dynamic exchange and reactivity between particles and gas-phase molecules. Dicarboxylic acids are ubiquitous in ambient atmosphere and the uptake of which may lead to substantial changes in hygroscopicity, absorption property, and light scattering of aerosol particles. This study investigates the diffusivity of dicarboxylic acids to the matrix of SOM particles. SOM was generated from dark ozonolysis of a-pinene in Harvard Environmental Chamber. The produced SOM particles were passed through an ozone scrubber to remove gas-phase chemistry before being led into a flask reactor, where gas-phase dicarboxylic acid was injected continuously and RH was varied from 5% to 85%. The probe dicarboxylic acids molecules including malonic acid and a-ketoglutaric acid have been investigated for the uptake to SOM particles. Organic composition in the outflow of the flask was measured with a high-resolution time-of-flight aerosol mass spectrometer. The mass fractions of tracer ions in total organic mass for both malonic acid and a-ketoglutaric acid increased substantially with the increase of RH values. The tracer ions of malonic acid were also more abundant in a-pinene SOM particles with increased gas-phase concentrations. These results suggest that the diffusion of the studied dicarboxylic acids molecules to a-pinene SOM particles was enhanced at increased RH values, which is possibly due to the phase transition of a-pinene SOM particles from non-liquid to liquid states. Therefore, particle phase state may be an important factor governing the diffusivity of dicarboxylic acids molecules to a-pinene SOM. Further dicarboxylic acids with various functional groups will be investigated to understand the effects of volatility and structure on their diffusivity.

Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

ClinicalTrials.gov

2017-09-28

Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

Systems Based Study of the Therapeutic Potential of Small Charged Molecules for the Inhibition of IL-1 Mediated Cartilage Degradation

PubMed Central

Kar, Saptarshi; Smith, David W.; Gardiner, Bruce S.; Grodzinsky, Alan J.

2016-01-01

Inflammatory cytokines are key drivers of cartilage degradation in post-traumatic osteoarthritis. Cartilage degradation mediated by these inflammatory cytokines has been extensively investigated using in vitro experimental systems. Based on one such study, we have developed a computational model to quantitatively assess the impact of charged small molecules intended to inhibit IL-1 mediated cartilage degradation. We primarily focus on the simplest possible computational model of small molecular interaction with the IL-1 system—direct binding of the small molecule to the active site on the IL-1 molecule itself. We first use the model to explore the uptake and release kinetics of the small molecule inhibitor by cartilage tissue. Our results show that negatively charged small molecules are excluded from the negatively charged cartilage tissue and have uptake kinetics in the order of hours. In contrast, the positively charged small molecules are drawn into the cartilage with uptake and release timescales ranging from hours to days. Using our calibrated computational model, we subsequently explore the effect of small molecule charge and binding constant on the rate of cartilage degradation. The results from this analysis indicate that the small molecules are most effective in inhibiting cartilage degradation if they are either positively charged and/or bind strongly to IL-1α, or both. Furthermore, our results showed that the cartilage structural homeostasis can be restored by the small molecule if administered within six days following initial tissue exposure to IL-1α. We finally extended the scope of the computational model by simulating the competitive inhibition of cartilage degradation by the small molecule. Results from this model show that small molecules are more efficient in inhibiting cartilage degradation by binding directly to IL-1α rather than binding to IL-1α receptors. The results from this study can be used as a template for the design and development of more pharmacologically effective osteoarthritis drugs, and to investigate possible therapeutic options. PMID:27977731

Effect of Grain Size on Differential Desorption of Volatile Species and on Non-ideal MHD Diffusivity

NASA Astrophysics Data System (ADS)

Zhao, Bo; Caselli, Paola; Li, Zhi-Yun

2018-05-01

We developed a chemical network for modeling the chemistry and non-ideal MHD effects from the collapsing dense molecular clouds to protostellar disks. First, we re-formulated the cosmic-ray desorption rate by considering the variations of desorption rate over the grain size distribution. We find that the differential desorption of volatile species is amplified by the grains larger than 0.1 μm, because larger grains are heated to a lower temperature by cosmic-rays and hence more sensitive to the variations in binding energies. As a result, atomic nitrogen N is ˜2 orders of magnitude more abundant than CO; N2H+ also becomes a few times more abundant than HCO+ due to the increased gas-phase N2. However, the changes in ionization fraction due to freeze-out and desorption only have minor effects on the non-ideal MHD diffusivities. Our chemical network confirms that the very small grains (VSGs: below a few 100 Å) weakens the efficiency of both ambipolar diffusion and Hall effect. In collapsing dense cores, a maximum ambipolar diffusion is achieved when truncating the MRN size distribution at 0.1 μm, and for a maximum Hall effect, the truncation occurs at 0.04 μm. We conclude that the grain size distribution is crucial to the differential depletion between CO and N2 related molecules, as well as to the non-ideal MHD diffusivities in dense cores.

Origin of CH+ in diffuse molecular clouds. Warm H2 and ion-neutral drift

NASA Astrophysics Data System (ADS)

Valdivia, Valeska; Godard, Benjamin; Hennebelle, Patrick; Gerin, Maryvonne; Lesaffre, Pierre; Le Bourlot, Jacques

2017-04-01

Context. Molecular clouds are known to be magnetised and to display a turbulent and complex structure where warm and cold phases are interwoven. The turbulent motions within molecular clouds transport molecules, and the presence of magnetic fields induces a relative velocity between neutrals and ions known as the ion-neutral drift (vd). These effects all together can influence the chemical evolution of the clouds. Aims: This paper assesses the roles of two physical phenomena which have previously been invoked to boost the production of CH+ under realistic physical conditions: the presence of warm H2 and the increased formation rate due to the ion-neutral drift. Methods: We performed ideal magnetohydrodynamical (MHD) simulations that include the heating and cooling of the multiphase interstellar medium (ISM), and where we treat dynamically the formation of the H2 molecule. In a post-processing step we compute the abundances of species at chemical equilibrium using a solver that we developed. The solver uses the physical conditions of the gas as input parameters, and can also prescribe the H2 fraction if needed. We validate our approach by showing that the H2 molecule generally has a much longer chemical evolution timescale compared to the other species. Results: We show that CH+ is efficiently formed at the edge of clumps, in regions where the H2 fraction is low (0.3-30%) but nevertheless higher than its equilibrium value, and where the gas temperature is high (≳ 300 K). We show that warm and out of equilibrium H2 increases the integrated column densities of CH+ by one order of magnitude up to values still 3-10 times lower than those observed in the diffuse ISM. We balance the Lorentz force with the ion-neutral drag to estimate the ion-drift velocities from our ideal MHD simulations. We find that the ion-neutral drift velocity distribution peaks around 0.04 km s-1, and that high drift velocities are too rare to have a significant statistical impact on the abundances of CH+. Compared to previous works, our multiphase simulations reduce the spread in vd, and our self-consistent treatment of the ionisation leads to much reduced vd. Nevertheless, our resolution study shows that this velocity distribution is not converged: the ion-neutral drift has a higher impact on CH+ at higher resolution. On the other hand, our ideal MHD simulations do not include ambipolar diffusion, which would yield lower drift velocities. Conclusions: Within these limitations, we conclude that warm H2 is a key ingredient in the efficient formation of CH+ and that the ambipolar diffusion has very little influence on the abundance of CH+, mainly due to the small drift velocities obtained. However, we point out that small-scale processes and other non-thermal processes not included in our MHD simulation may be of crucial importance, and higher resolution studies with better controlled dissipation processes are needed.

Reaction Kinetics of Water Molecules with Oxygen Vacancies on Rutile TiO 2(110)

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

Petrik, Nikolay G.; Kimmel, Gregory A.

2015-09-16

The formation of bridging hydroxyls (OHb) via reactions of water molecules with oxygen vacancies (VO) on reduced TiO 2(110) surfaces is studied using infrared reflection-absorption spectroscopy (IRAS), electron-stimulated desorption (ESD), and photon-stimulated desorption (PSD). Narrow IRAS peaks at 2737 cm-1 and 3711 cm -1 are observed for stretching vibrations of OD b and OH b on TiO 2(110), respectively. IRAS measurements with s- and p-polarized light demonstrate that the bridging hydroxyls are oriented normal to the (110) surface. The IR peaks disappear after the sample is exposed to O 2 or annealed in the temperature range of 400 – 600more » K (correlating with the temperature at which pairs of OHb’s reform water and then desorb), which is consistent with their identification as bridging hydroxyls. We have studied the kinetics of water reacting with the vacancies by monitoring the formation of bridging hydroxyls (using IRAS) as a function of the annealing temperature for a small amount of water initially dosed on the TiO 2(110) at low temperature. Separate experiments have also monitored the loss of water molecules (using water ESD) and vacancies (using the CO photooxidation reaction) due to the reactions of water molecules with the vacancies. All three techniques show that the reaction rate becomes appreciable for T > 150 K and that the reactions largely complete for T > 250 K. The temperature-dependent water-VO reaction kinetics are consistent with a Gaussian distribution of activation energies with E a = 0.545 eV, ΔE a(FWHM) = 0.125 eV, and a “normal” prefactor, v = 10 12 s -1. In contrast, a single activation energy with a physically reasonable prefactor does not fit the data well. Our experimental activation energy is close to theoretical estimates for the diffusion of water molecules along the Ti 5c rows on the reduced TiO 2(110) surface, which suggests that the diffusion of water controls the water – V O reaction rate.« less

Antibody-enabled small-molecule drug discovery.

PubMed

Lawson, Alastair D G

2012-06-29

Although antibody-based therapeutics have become firmly established as medicines for serious diseases, the value of antibodies as tools in the early stages of small-molecule drug discovery is only beginning to be realized. In particular, antibodies may provide information to reduce risk in small-molecule drug discovery by enabling the validation of targets and by providing insights into the design of small-molecule screening assays. Moreover, antibodies can act as guides in the quest for small molecules that have the ability to modulate protein-protein interactions, which have traditionally only been considered to be tractable targets for biological drugs. The development of small molecules that have similar therapeutic effects to current biologics has the potential to benefit a broader range of patients at earlier stages of disease.

Reaction rates for a generalized reaction-diffusion master equation

DOE PAGES

Hellander, Stefan; Petzold, Linda

2016-01-19

It has been established that there is an inherent limit to the accuracy of the reaction-diffusion master equation. Specifically, there exists a fundamental lower bound on the mesh size, below which the accuracy deteriorates as the mesh is refined further. In this paper we extend the standard reaction-diffusion master equation to allow molecules occupying neighboring voxels to react, in contrast to the traditional approach in which molecules react only when occupying the same voxel. We derive reaction rates, in two dimensions as well as three dimensions, to obtain an optimal match to the more fine-grained Smoluchowski model, and show inmore » two numerical examples that the extended algorithm is accurate for a wide range of mesh sizes, allowing us to simulate systems that are intractable with the standard reaction-diffusion master equation. In addition, we show that for mesh sizes above the fundamental lower limit of the standard algorithm, the generalized algorithm reduces to the standard algorithm. We derive a lower limit for the generalized algorithm which, in both two dimensions and three dimensions, is on the order of the reaction radius of a reacting pair of molecules.« less

Reaction rates for a generalized reaction-diffusion master equation

PubMed Central

Hellander, Stefan; Petzold, Linda

2016-01-01

It has been established that there is an inherent limit to the accuracy of the reaction-diffusion master equation. Specifically, there exists a fundamental lower bound on the mesh size, below which the accuracy deteriorates as the mesh is refined further. In this paper we extend the standard reaction-diffusion master equation to allow molecules occupying neighboring voxels to react, in contrast to the traditional approach in which molecules react only when occupying the same voxel. We derive reaction rates, in two dimensions as well as three dimensions, to obtain an optimal match to the more fine-grained Smoluchowski model, and show in two numerical examples that the extended algorithm is accurate for a wide range of mesh sizes, allowing us to simulate systems that are intractable with the standard reaction-diffusion master equation. In addition, we show that for mesh sizes above the fundamental lower limit of the standard algorithm, the generalized algorithm reduces to the standard algorithm. We derive a lower limit for the generalized algorithm which, in both two dimensions and three dimensions, is on the order of the reaction radius of a reacting pair of molecules. PMID:26871190

The diffuse interstellar bands: a tracer for organics in the diffuse interstellar medium?

NASA Technical Reports Server (NTRS)

Salama, F.

1998-01-01

The diffuse interstellar bands (DIBs) are absorption bands seen in the spectra of stars obscured by interstellar dust. DIBs are recognized as a tracer for free, organic molecules in the diffuse interstellar medium (ISM). The potential molecular carriers for the DIBs are discussed with an emphasis on neutral and ionized polycyclic aromatic hydrocarbons (PAHs) for which the most focused effort has been made to date. From the combined astronomical, laboratory and theoretical study, it is concluded that a distribution of free neutral and ionized complex organics (PAHs, fullerenes, unsaturated hydrocarbons) represents the most promising class of candidates to account for the DIBs. The case for aromatic hydrocarbons appears particularly strong. The implied widespread distribution of complex organics in the diffuse ISM bears profound implications for our understanding of the chemical complexity of the ISM, the evolution of prebiotic molecules and its impact on the origin and the evolution of life on early Earth through the exogenous delivery (cometary encounters and metoritic bombardments) of prebiotic organics.

Percolation Diffusion into Self-Assembled Mesoporous Silica Microfibres

PubMed Central

Canning, John; Huyang, George; Ma, Miles; Beavis, Alison; Bishop, David; Cook, Kevin; McDonagh, Andrew; Shi, Dongqi; Peng, Gang-Ding; Crossley, Maxwell J.

2014-01-01

Percolation diffusion into long (11.5 cm) self-assembled, ordered mesoporous microfibres is studied using optical transmission and laser ablation inductive coupled mass spectrometry (LA-ICP-MS). Optical transmission based diffusion studies reveal rapid penetration (<5 s, D > 80 μm2∙s−1) of Rhodamine B with very little percolation of larger molecules such as zinc tetraphenylporphyrin (ZnTPP) observed under similar loading conditions. The failure of ZnTPP to enter the microfibre was confirmed, in higher resolution, using LA-ICP-MS. In the latter case, LA-ICP-MS was used to determine the diffusion of zinc acetate dihydrate, D~3 × 10−4 nm2∙s−1. The large differences between the molecules are accounted for by proposing ordered solvent and structure assisted accelerated diffusion of the Rhodamine B based on its hydrophilicity relative to the zinc compounds. The broader implications and applications for filtration, molecular sieves and a range of devices and uses are described. PMID:28348290

Coupling between diffusion and orientation of pentacene molecules on an organic surface.

PubMed

Rotter, Paul; Lechner, Barbara A J; Morherr, Antonia; Chisnall, David M; Ward, David J; Jardine, Andrew P; Ellis, John; Allison, William; Eckhardt, Bruno; Witte, Gregor

2016-04-01

The realization of efficient organic electronic devices requires the controlled preparation of molecular thin films and heterostructures. As top-down structuring methods such as lithography cannot be applied to van der Waals bound materials, surface diffusion becomes a structure-determining factor that requires microscopic understanding. Scanning probe techniques provide atomic resolution, but are limited to observations of slow movements, and therefore constrained to low temperatures. In contrast, the helium-3 spin-echo (HeSE) technique achieves spatial and time resolution on the nm and ps scale, respectively, thus enabling measurements at elevated temperatures. Here we use HeSE to unveil the intricate motion of pentacene admolecules diffusing on a chemisorbed monolayer of pentacene on Cu(110) that serves as a stable, well-ordered organic model surface. We find that pentacene moves along rails parallel and perpendicular to the surface molecules. The experimental data are explained by admolecule rotation that enables a switching between diffusion directions, which extends our molecular level understanding of diffusion in complex organic systems.

Chemical application of diffusion quantum Monte Carlo

NASA Technical Reports Server (NTRS)

Reynolds, P. J.; Lester, W. A., Jr.

1984-01-01

The diffusion quantum Monte Carlo (QMC) method gives a stochastic solution to the Schroedinger equation. This approach is receiving increasing attention in chemical applications as a result of its high accuracy. However, reducing statistical uncertainty remains a priority because chemical effects are often obtained as small differences of large numbers. As an example, the single-triplet splitting of the energy of the methylene molecule CH sub 2 is given. The QMC algorithm was implemented on the CYBER 205, first as a direct transcription of the algorithm running on the VAX 11/780, and second by explicitly writing vector code for all loops longer than a crossover length C. The speed of the codes relative to one another as a function of C, and relative to the VAX, are discussed. The computational time dependence obtained versus the number of basis functions is discussed and this is compared with that obtained from traditional quantum chemistry codes and that obtained from traditional computer architectures.

Photo-induced Mass Transport through Polymer Networks

NASA Astrophysics Data System (ADS)

Meng, Yuan; Anthamatten, Mitchell

2014-03-01

Among adaptable materials, photo-responsive polymers are especially attractive as they allow for spatiotemporal stimuli and response. We have recently developed a macromolecular network capable of photo-induced mass transport of covalently bound species. The system comprises of crosslinked chains that form an elastic network and photosensitive fluorescent arms that become mobile upon irradiation. We form loosely crosslinked polymer networks by Michael-Addition between multifunctional thiols and small molecule containing acrylate end-groups. The arms are connected to the network by allyl sulfide, that undergoes addition-fragmentation chain transfer (AFCT) in the presence of free radicals, releasing diffusible fluorophore. The networks are loaded with photoinitiator to allow for spatial modulation of the AFCT reactions. FRAP experiments within bulk elastomers are conducted to establish correlations between the fluorophore's diffusion coefficient and experimental variables such as network architecture, temperature and UV intensity. Photo-induced mass transport between two contacted films is demonstrated, and release of fluorophore into a solvent is investigated. Spatial and temporal control of mass transport could benefit drug release, printing, and sensing applications.

Running and tumbling with E. coli in polymeric solutions

PubMed Central

Patteson, A. E.; Gopinath, A.; Goulian, M.; Arratia, P. E.

2015-01-01

Run-and-tumble motility is widely used by swimming microorganisms including numerous prokaryotic and eukaryotic organisms. Here, we experimentally investigate the run-and-tumble dynamics of the bacterium E. coli in polymeric solutions. We find that even small amounts of polymer in solution can drastically change E. coli dynamics: cells tumble less and their velocity increases, leading to an enhancement in cell translational diffusion and a sharp decline in rotational diffusion. We show that suppression of tumbling is due to fluid viscosity while the enhancement in swimming speed is mainly due to fluid elasticity. Visualization of single fluorescently labeled DNA polymers reveals that the flow generated by individual E. coli is sufficiently strong to stretch polymer molecules and induce elastic stresses in the fluid, which in turn can act on the cell in such a way to enhance its transport. Our results show that the transport and spread of chemotactic cells can be independently modified and controlled by the fluid material properties. PMID:26507950

Chemically frozen multicomponent boundary layer theory of salt and/or ash deposition rates from combustion gases

NASA Technical Reports Server (NTRS)

Rosner, D. E.; Chen, B.-K.; Fryburg, G. C.; Kohl, F. J.

1979-01-01

There is increased interest in, and concern about, deposition and corrosion phenomena in combustion systems containing inorganic condensible vapors and particles (salts, ash). To meet the need for a computationally tractable deposition rate theory general enough to embrace multielement/component situations of current and future gas turbine and magnetogasdynamic interest, a multicomponent chemically 'frozen' boundary layer (CFBL) deposition theory is presented and its applicability to the special case of Na2SO4 deposition from seeded laboratory burner combustion products is demonstrated. The coupled effects of Fick (concentration) diffusion and Soret (thermal) diffusion are included, along with explicit corrections for effects of variable properties and free stream turbulence. The present formulation is sufficiently general to include the transport of particles provided they are small enough to be formally treated as heavy molecules. Quantitative criteria developed to delineate the domain of validity of CFBL-rate theory suggest considerable practical promise for the present framework, which is characterized by relatively modest demands for new input information and computer time.

Primary intestinal lymphangiectasia diagnosed by capsule endoscopy and double balloon enteroscopy

PubMed Central

Oh, Tak Geun; Chung, Joo Won; Kim, Hee Man; Han, Seok-Joo; Lee, Jin Sung; Park, Jung Yeob; Song, Si Young

2011-01-01

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lymphatics and the development of protein-losing enteropathy. Patients with PIL develop hypoalbuminemia, hypocalcemia, lymphopenia and hypogammaglobulinemia, and present with bilateral lower limb edema, fatigue, abdominal pain and diarrhea. Endoscopy reveals diffusely elongated, circumferential and polypoid mucosae covered with whitish enlarged villi, all of which indicate intestinal lymphangiectasia. Diagnosis is confirmed by characteristic tissue pathology, which includes dilated intestinal lymphatics with diffusely swollen mucosa and enlarged villi. The prevalence of PIL has increased since the introduction of capsule endoscopy. The etiology and prevalence of PIL remain unknown. Some studies have reported that several genes and regulatory molecules for lymphangiogenesis are related to PIL. We report the case of a patient with PIL involving the entire small bowel that was confirmed by capsule endoscopy and double-balloon enteroscopy-guided tissue pathology who carried a deletion on chromosome 4q25. The relationship between this deletion on chromosome 4 and PIL remains to be investigated. PMID:22110841

MreB-Dependent Organization of the E. coli Cytoplasmic Membrane Controls Membrane Protein Diffusion.

PubMed

Oswald, Felix; Varadarajan, Aravindan; Lill, Holger; Peterman, Erwin J G; Bollen, Yves J M

2016-03-08

The functional organization of prokaryotic cell membranes, which is essential for many cellular processes, has been challenging to analyze due to the small size and nonflat geometry of bacterial cells. Here, we use single-molecule fluorescence microscopy and three-dimensional quantitative analyses in live Escherichia coli to demonstrate that its cytoplasmic membrane contains microdomains with distinct physical properties. We show that the stability of these microdomains depends on the integrity of the MreB cytoskeletal network underneath the membrane. We explore how the interplay between cytoskeleton and membrane affects trans-membrane protein (TMP) diffusion and reveal that the mobility of the TMPs tested is subdiffusive, most likely caused by confinement of TMP mobility by the submembranous MreB network. Our findings demonstrate that the dynamic architecture of prokaryotic cell membranes is controlled by the MreB cytoskeleton and regulates the mobility of TMPs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Running and tumbling with E. coli in polymeric solutions

NASA Astrophysics Data System (ADS)

Patteson, A. E.; Gopinath, A.; Goulian, M.; Arratia, P. E.

2015-10-01

Run-and-tumble motility is widely used by swimming microorganisms including numerous prokaryotic and eukaryotic organisms. Here, we experimentally investigate the run-and-tumble dynamics of the bacterium E. coli in polymeric solutions. We find that even small amounts of polymer in solution can drastically change E. coli dynamics: cells tumble less and their velocity increases, leading to an enhancement in cell translational diffusion and a sharp decline in rotational diffusion. We show that suppression of tumbling is due to fluid viscosity while the enhancement in swimming speed is mainly due to fluid elasticity. Visualization of single fluorescently labeled DNA polymers reveals that the flow generated by individual E. coli is sufficiently strong to stretch polymer molecules and induce elastic stresses in the fluid, which in turn can act on the cell in such a way to enhance its transport. Our results show that the transport and spread of chemotactic cells can be independently modified and controlled by the fluid material properties.

A combination of spin diffusion methods for the determination of protein-ligand complex structural ensembles.

PubMed

Pilger, Jens; Mazur, Adam; Monecke, Peter; Schreuder, Herman; Elshorst, Bettina; Bartoschek, Stefan; Langer, Thomas; Schiffer, Alexander; Krimm, Isabelle; Wegstroth, Melanie; Lee, Donghan; Hessler, Gerhard; Wendt, K-Ulrich; Becker, Stefan; Griesinger, Christian

2015-05-26

Structure-based drug design (SBDD) is a powerful and widely used approach to optimize affinity of drug candidates. With the recently introduced INPHARMA method, the binding mode of small molecules to their protein target can be characterized even if no spectroscopic information about the protein is known. Here, we show that the combination of the spin-diffusion-based NMR methods INPHARMA, trNOE, and STD results in an accurate scoring function for docking modes and therefore determination of protein-ligand complex structures. Applications are shown on the model system protein kinase A and the drug targets glycogen phosphorylase and soluble epoxide hydrolase (sEH). Multiplexing of several ligands improves the reliability of the scoring function further. The new score allows in the case of sEH detecting two binding modes of the ligand in its binding site, which was corroborated by X-ray analysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery.

PubMed

Dolor, Aaron; Szoka, Francis C

2018-06-04

Collagen and hyaluronan are the most abundant components of the extracellular matrix (ECM) and their overexpression in tumors is linked to increased tumor growth and metastasis. These ECM components contribute to a protective tumor microenvironment by supporting a high interstitial fluid pressure and creating a tortuous setting for the convection and diffusion of chemotherapeutic small molecules, antibodies, and nanoparticles in the tumor interstitial space. This review focuses on the research efforts to deplete extracellular collagen with collagenases to normalize the tumor microenvironment. Although collagen synthesis inhibitors are in clinical development, the use of collagenases is contentious and clinically untested in cancer patients. Pretreatment of murine tumors with collagenases increased drug uptake and diffusion 2-10-fold. This modest improvement resulted in decreased tumor growth, but the benefits of collagenase treatment are confounded by risks of toxicity from collagen breakdown in healthy tissues. In this review, we evaluate the published in vitro and in vivo benefits and limitations of collagenase treatment to improve drug delivery.

Small Molecule Chemical Probes of MicroRNA Function

PubMed Central

Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R.; Disney, Matthew D.

2015-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as strides are made to understand small molecule recognition of RNA from a fundamental perspective. PMID:25500006

Single molecule analysis of B cell receptor motion during signaling activation

NASA Astrophysics Data System (ADS)

Rey Suarez, Ivan; Koo, Peter; Zhou, Shu; Wheatley, Brittany; Song, Wenxia; Mochrie, Simon; Upadhyaya, Arpita

B cells are an essential part of the adaptive immune system. They patrol the body for signs of infection in the form of antigen on the surface of antigen presenting cells. B cell receptor (BCR) binding to antigen induces a signaling cascade that leads to B cell activation and spreading. During activation, BCR form signaling microclusters that later coalesce as the cell contracts. We have studied the dynamics of BCRs on activated murine primary B cells using single particle tracking. The tracks are analyzed using perturbation expectation-maximization (pEM), a systems-level analysis, which allows identification of different short-time diffusive states from single molecule tracks. We identified four dominant diffusive states, two of which correspond to BCRs interacting with signaling molecules. For wild-type cells, the number of BCR in signaling states increases as the cell spreads and then decreases during cell contraction. In contrast, cells lacking the actin regulatory protein, N-WASP, are unable to contract and BCRs remain in the signaling states for longer times. These observations indicate that actin cytoskeleton dynamics modulate BCR diffusion and clustering. Our results provide novel information regarding the timescale of interaction between BCR and signaling molecules.

Properties of interfaces and transport across them.

PubMed

Cabezas, H

2000-01-01

Much of the biological activity in cell cytoplasm occurs in compartments some of which may be formed, as suggested in this book, by phase separation, and many of the functions of such compartments depend on the transport or exchange of molecules across interfaces. Thus a fundamentally based discussion of the properties of phases, interfaces, and diffusive transport across interfaces has been given to further elucidate these phenomena. An operational criterion for the width of interfaces is given in terms of molecular and physical arguments, and the properties of molecules inside phases and interfaces are discussed in terms of molecular arguments. In general, the properties of the interface become important when the molecules diffusing across are smaller than the width of the interface. Equilibrium partitioning, Donnan phenomena, and electrochemical potentials at interfaces are also discussed in detail. The mathematical expressions for modeling transport across interfaces are discussed in detail. These describe a practical and detailed model for transport across interfaces. For molecules smaller than the width of the interface, this includes a detailed model for diffusion inside the interface. Last, the question of the time scale for phase formation and equilibration in biological systems is discussed.

Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

ClinicalTrials.gov

2017-05-23

Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

Single-Molecule Resolution of Antimicrobial Peptide Interactions with Supported Lipid A Bilayers.

PubMed

Nelson, Nathaniel; Schwartz, Daniel K

2018-06-05

The molecular interactions between antimicrobial peptides (AMPs) and lipid A-containing supported lipid bilayers were probed using single-molecule total internal reflection fluorescence microscopy. Hybrid supported lipid bilayers with lipid A outer leaflets and phospholipid (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)) inner leaflets were prepared and characterized, and the spatiotemporal trajectories of individual fluorescently labeled LL37 and Melittin AMPs were determined as they interacted with the bilayer surfaces comprising either monophosphoryl or diphosphoryl lipid A (from Escherichia coli) to determine the impact of electrostatic interactions. Large numbers of trajectories were obtained and analyzed to obtain the distributions of surface residence times and the statistics of the spatial trajectories. Interestingly, the AMP species were sensitive to subtle differences in the charge of the lipid, with both peptides diffusing more slowly and residing longer on the diphosphoryl lipid A. Furthermore, the single-molecule dynamics indicated a qualitative difference between the behavior of AMPs on hybrid Lipid A bilayers and on those composed entirely of DOPE. Whereas AMPs interacting with a DOPE bilayer exhibited two-dimensional Brownian diffusion with a diffusion coefficient of ∼1.7 μm 2 /s, AMPs adsorbed to the lipid A surface exhibited much slower apparent diffusion (on the order of ∼0.1 μm 2 /s) and executed intermittent trajectories that alternated between two-dimensional Brownian diffusion and desorption-mediated three-dimensional flights. Overall, these findings suggested that bilayers with lipid A in the outer leaflet, as it is in bacterial outer membranes, are valuable model systems for the study of the initial stage of AMP-bacterium interactions. Furthermore, single-molecule dynamics was sensitive to subtle differences in electrostatic interactions between cationic AMPs and monovalent or divalent anionic lipid A moieties. Copyright © 2018 Biophysical Society. All rights reserved.

Tracing compartment exchange by NMR diffusometry: Water in lithium-exchanged low-silica X zeolites

NASA Astrophysics Data System (ADS)

Lauerer, A.; Kurzhals, R.; Toufar, H.; Freude, D.; Kärger, J.

2018-04-01

The two-region model for analyzing signal attenuation in pulsed field gradient (PFG) NMR diffusion studies with molecules in compartmented media implies that, on their trajectory, molecules get from one region (one type of compartment) into the other one with a constant (i.e. a time-invariant) probability. This pattern has proved to serve as a good approach for considering guest diffusion in beds of nanoporous host materials, with the two regions ("compartments") identified as the intra- and intercrystalline pore spaces. It is obvious, however, that the requirements of the application of the two-region model are not strictly fulfilled given the correlation between the covered diffusion path lengths in the intracrystalline pore space and the probability of molecular "escape" from the individual crystallites. On considering water diffusion in lithium-exchanged low-silica X zeolite, we are now assuming a different position since this type of material is known to offer "traps" in the trajectories of the water molecules. Now, on attributing the water molecules in the traps and outside of the traps to these two types of regions, we perfectly comply with the requirements of the two-region model. We do, moreover, benefit from the option of high-resolution measurements owing to the combination of magic angle spinning (MAS) with PFG NMR. Data analysis via the two-region model under inclusion of the influence of nuclear magnetic relaxation yields satisfactory agreement between experimental evidence and theoretical estimates. Limitations in accuracy are shown to result from the fact that mass transfer outside of the traps is too complicated for being adequately reflected by simple Fick's laws with but one diffusivity.

Hindered diffusion of high molecular weight compounds in brain extracellular microenvironment measured with integrative optical imaging.

PubMed

Nicholson, C; Tao, L

1993-12-01

This paper describes the theory of an integrative optical imaging system and its application to the analysis of the diffusion of 3-, 10-, 40-, and 70-kDa fluorescent dextran molecules in agarose gel and brain extracellular microenvironment. The method uses a precisely defined source of fluorescent molecules pressure ejected from a micropipette, and a detailed theory of the intensity contributions from out-of-focus molecules in a three-dimensional medium to a two-dimensional image. Dextrans tagged with either tetramethylrhodamine or Texas Red were ejected into 0.3% agarose gel or rat cortical slices maintained in a perfused chamber at 34 degrees C and imaged using a compound epifluorescent microscope with a 10 x water-immersion objective. About 20 images were taken at 2-10-s intervals, recorded with a cooled CCD camera, then transferred to a 486 PC for quantitative analysis. The diffusion coefficient in agarose gel, D, and the apparent diffusion coefficient, D*, in brain tissue were determined by fitting an integral expression relating the measured two-dimensional image intensity to the theoretical three-dimensional dextran concentration. The measurements in dilute agarose gel provided a reference value of D and validated the method. Values of the tortuosity, lambda = (D/D*)1/2, for the 3- and 10-kDa dextrans were 1.70 and 1.63, respectively, which were consistent with previous values derived from tetramethylammonium measurements in cortex. Tortuosities for the 40- and 70-kDa dextrans had significantly larger values of 2.16 and 2.25, respectively. This suggests that the extracellular space may have local constrictions that hinder the diffusion of molecules above a critical size that lies in the range of many neurotrophic compounds.

Mass transfer of large molecules through collagen and collagen-silica hybrid membranes

NASA Astrophysics Data System (ADS)

Jofre-Lora, Pedro

Diabetes is a growing concern in the United States and around the world that must be addressed through new treatment options. Current standard treatment options of diabetes are limiting and have tremendous impacts on patient's lives. Emerging therapies, such as the implantation of encapsulated islets, are promising treatment options, but have not yet materialized due to unsolved problems with material properties. Hybrid silica-collagen membranes address some of these unsolved problems and are a promising material for cell encapsulation. However, the mass transfer properties of large molecules, such as insulin, TNF-alpha, IL1beta, and other important proteins in the etiology of diabetes, through these hybrid membranes are poorly characterized. In order to begin characterizing these properties, a device was constructed to accurately and efficiently measure the mass transfer of other similar large molecules, fluorescein isothiocyanate dextrans (FITC-dextran), through collagen-silica hybrid membranes. The device was used to measure diffusion coefficients of 4, 20, 40, and 150 kDa FITC-dextrans through non-silicified and silicified samples of 200 and 1000 Pa porcine skin collagen. Diffusion coefficients were found to be in the 10-7-10-6 cm2s -1 range, which is in agreement with previously published data for similar molecules through similar hydrogels. The effects of collagen stiffness, FITC-dextran molecular weight, and silicification treatment on diffusion were investigated. It was found that collagen stiffness and FITC-dextran molecular weight had a negative correlation with diffusion, whereas silicification treatment had no global impact on diffusion. The device created, and the results of this preliminary investigation, can be used to develop collagen-silica hybrid membranes as an alternative material for cell encapsulation in a forward-design manner.

Medium-Bandgap Small-Molecule Donors Compatible with Both Fullerene and Nonfullerene Acceptors.

PubMed

Huo, Yong; Yan, Cenqi; Kan, Bin; Liu, Xiao-Fei; Chen, Li-Chuan; Hu, Chen-Xia; Lau, Tsz-Ki; Lu, Xinhui; Sun, Chun-Lin; Shao, Xiangfeng; Chen, Yongsheng; Zhan, Xiaowei; Zhang, Hao-Li

2018-03-21

Much effort has been devoted to the development of new donor materials for small-molecule organic solar cells due to their inherent advantages of well-defined molecular weight, easy purification, and good reproducibility in photovoltaic performance. Herein, we report two small-molecule donors that are compatible with both fullerene and nonfullerene acceptors. Both molecules consist of an (E)-1,2-di(thiophen-2-yl)ethane-substituted (TVT-substituted) benzo[1,2-b:4,5-b']dithiophene (BDT) as the central unit, and two rhodanine units as the terminal electron-withdrawing groups. The central units are modified with either alkyl side chains (DRBDT-TVT) or alkylthio side chains (DRBDT-STVT). Both molecules exhibit a medium bandgap with complementary absorption and proper energy level offset with typical acceptors like PC 71 BM and IDIC. The optimized devices show a decent power conversion efficiency (PCE) of 6.87% for small-molecule organic solar cells and 6.63% for nonfullerene all small-molecule organic solar cells. Our results reveal that rationally designed medium-bandgap small-molecule donors can be applied in high-performance small-molecule organic solar cells with different types of acceptors.

Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs.

PubMed

Disney, Matthew D; Winkelsas, Audrey M; Velagapudi, Sai Pradeep; Southern, Mark; Fallahi, Mohammad; Childs-Disney, Jessica L

2016-06-17

The development of small molecules that target RNA is challenging yet, if successful, could advance the development of chemical probes to study RNA function or precision therapeutics to treat RNA-mediated disease. Previously, we described Inforna, an approach that can mine motifs (secondary structures) within target RNAs, which is deduced from the RNA sequence, and compare them to a database of known RNA motif-small molecule binding partners. Output generated by Inforna includes the motif found in both the database and the desired RNA target, lead small molecules for that target, and other related meta-data. Lead small molecules can then be tested for binding and affecting cellular (dys)function. Herein, we describe Inforna 2.0, which incorporates all known RNA motif-small molecule binding partners reported in the scientific literature, a chemical similarity searching feature, and an improved user interface and is freely available via an online web server. By incorporation of interactions identified by other laboratories, the database has been doubled, containing 1936 RNA motif-small molecule interactions, including 244 unique small molecules and 1331 motifs. Interestingly, chemotype analysis of the compounds that bind RNA in the database reveals features in small molecule chemotypes that are privileged for binding. Further, this updated database expanded the number of cellular RNAs to which lead compounds can be identified.

Redox active molecules cytochrome c and vitamin C enhance heme-enzyme peroxidations by serving as non-specific agents for redox relay

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

Gade, Sudeep Kumar; Bhattacharya, Subarna; Manoj, Kelath Murali, E-mail: satyamjayatu@yahoo.com

2012-03-09

Highlights: Black-Right-Pointing-Pointer At low concentrations, cytochrome c/vitamin C do not catalyze peroxidations. Black-Right-Pointing-Pointer But low levels of cytochrome c/vitamin C enhance diverse heme peroxidase activities. Black-Right-Pointing-Pointer Enhancement positively correlates to the concentration of peroxide in reaction. Black-Right-Pointing-Pointer Reducible additives serve as non-specific agents for redox relay in the system. Black-Right-Pointing-Pointer Insight into electron transfer processes in routine and oxidative-stress states. -- Abstract: We report that incorporation of very low concentrations of redox protein cytochrome c and redox active small molecule vitamin C impacted the outcome of one-electron oxidations mediated by structurally distinct plant/fungal heme peroxidases. Evidence suggests that cytochrome cmore » and vitamin C function as a redox relay for diffusible reduced oxygen species in the reaction system, without invoking specific or affinity-based molecular interactions for electron transfers. The findings provide novel perspectives to understanding - (1) the promiscuous role of cytochrome b{sub 5} in the metabolism mediated by liver microsomal xenobiotic metabolizing systems and (2) the roles of antioxidant molecules in affording relief from oxidative stress.« less

Nonideality in diffusion of ionic and hydrophobic solutes and pair dynamics in water-acetone mixtures of varying composition.

PubMed

Gupta, Rini; Chandra, Amalendu

2007-07-14

We have performed a series of molecular dynamics simulations of water-acetone mixtures containing either an ionic solute or a neutral hydrophobic solute to study the extent of nonideality in the dynamics of these solutes with variation of composition of the mixtures. The diffusion coefficients of the charged solutes, both cationic and anionic, are found to change nonmonotonically with the composition of the mixtures showing strong nonideality of their dynamics. Also, the extent of nonideality in the diffusion of these charged solutes is found to be similar to the nonideality that is observed for the diffusion and orientational relaxation of water and acetone molecules in these mixtures which show a somewhat similar changes in the solvation characteristics of charged and dipolar solutes with changes of composition of water-acetone mixtures. The diffusion of the hydrophobic solute, however, shows a monotonic increase with increase of acetone concentration showing its different solvation characteristics as compared to the charged and dipolar solutes. The links between the nonideality in diffusion and solvation structures are further confirmed through calculations of the relevant solute-solvent and solvent-solvent radial distribution functions for both ionic and hydrophobic solutes. We have also calculated various pair dynamical properties such as the relaxation of water-water and acetone-water hydrogen bonds and residence dynamics of water molecules in water and acetone hydration shells. The lifetimes of both water-water and acetone-water hydrogen bonds and also the residence times of water molecules are found to increase steadily with increase in acetone concentration. No maximum or minimum was found in the composition dependence of these pair dynamical quantities. The lifetimes of water-water hydrogen bonds are always found to be longer than that of acetone-water hydrogen bonds in these mixtures. The residence times of water molecules are also found to follow a similar trend.

Solute diffusion through fibrotic tissue formed around protective cage system for implantable devices.

PubMed

Prihandana, Gunawan Setia; Ito, Hikaru; Tanimura, Kohei; Yagi, Hiroshi; Hori, Yuki; Soykan, Orhan; Sudo, Ryo; Miki, Norihisa

2015-08-01

This article presents the concept of an implantable cage system that can house and protect implanted biomedical sensing and therapeutic devices in the body. Cylinder-shaped cages made of porous polyvinyl alcohol (PVA) sheets with an 80-µm pore size and/or stainless steel meshes with 0.54-mm openings were implanted subcutaneously in the dorsal region of rats for 5 weeks. Analysis of the explanted cages showed the formation of fibrosis tissue around the cages. PVA cages had fibrotic tissue growing mostly along the outer surface of cages, while stainless steel cages had fibrotic tissue growing into the inside surface of the cage structure, due to the larger porosity of the stainless steel meshes. As the detection of target molecules with short time lags for biosensors and mass transport with low diffusion resistance into and out of certain therapeutic devices are critical for the success of such devices, we examined whether the fibrous tissue formed around the cages were permeable to molecules of our interest. For that purpose, bath diffusion and microfluidic chamber diffusion experiments using solutions containing the target molecules were performed. Diffusion of sodium, potassium and urea through the fibrosis tissue was confirmed, thus suggesting the potential of these cylindrical cages surrounded by fibrosis tissue to successfully encase implantable sensors and therapeutic apparatus. © 2014 Wiley Periodicals, Inc.

Modeling the effect of glutamate diffusion and uptake on NMDA and non-NMDA receptor saturation.

PubMed Central

Holmes, W R

1995-01-01

One- and two-dimensional models of glutamate diffusion, uptake, and binding in the synaptic cleft were developed to determine if the release of single vesicles of glutamate would saturate NMDA and non-NMDA receptors. Ranges of parameter values were used in the simulations to determine the conditions when saturation could occur. Single vesicles of glutamate did not saturate NMDA receptors unless diffusion was very slow and the number of glutamate molecules in a vesicle was large. However, the release of eight vesicles at 400 Hz caused NMDA receptor saturation for all parameter values tested. Glutamate uptake was found to reduce NMDA receptor saturation, but the effect was smaller than that of changes in the diffusion coefficient or in the number of glutamate molecules in a vesicle. Non-NMDA receptors were not saturated unless diffusion was very slow and the number of glutamate molecules in a vesicle was large. The release of eight vesicles at 400 Hz caused significant non-NMDA receptor desensitization. The results suggest that NMDA and non-NMDA receptors are not saturated by single vesicles of glutamate under usual conditions, and that tetanic input, of the type typically used to induce long-term potentiation, will increase calcium influx by increasing receptor binding as well as by reducing voltage-dependent block of NMDA receptors. Images FIGURE 1 PMID:8580317

Mapping the Small Molecule Interactome by Mass Spectrometry.

PubMed

Flaxman, Hope A; Woo, Christina M

2018-01-16

Mapping small molecule interactions throughout the proteome provides the critical structural basis for functional analysis of their impact on biochemistry. However, translation of mass spectrometry-based proteomics methods to directly profile the interaction between a small molecule and the whole proteome is challenging because of the substoichiometric nature of many interactions, the diversity of covalent and noncovalent interactions involved, and the subsequent computational complexity associated with their spectral assignment. Recent advances in chemical proteomics have begun fill this gap to provide a structural basis for the breadth of small molecule-protein interactions in the whole proteome. Innovations enabling direct characterization of the small molecule interactome include faster, more sensitive instrumentation coupled to chemical conjugation, enrichment, and labeling methods that facilitate detection and assignment. These methods have started to measure molecular interaction hotspots due to inherent differences in local amino acid reactivity and binding affinity throughout the proteome. Measurement of the small molecule interactome is producing structural insights and methods for probing and engineering protein biochemistry. Direct structural characterization of the small molecule interactome is a rapidly emerging area pushing new frontiers in biochemistry at the interface of small molecules and the proteome.

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

Patel, TN; Park, AHA; Bantat, S

The limited permeability of the E. coli outer membrane can significantly hinder whole-cell biocatalyst performance. In this study, the SARS coronavirus small envelope protein (SCVE) was expressed in E. coli cells previously engineered for periplasmic expression of carbonic anhydrase (CA) activity. This maneuver increased small molecule uptake by the cells, resulting in increased apparent CA activity of the biocatalysts. The enhancements in activity were quantified using methods developed for traditional heterogeneous catalysis. The expression of the SCVE protein was found to significantly reduce the Thiele moduli (phi), as well as increase the effectiveness factors (eta), effective diffusivities (D-e), and permeabilitiesmore » (P) of the biocatalysts. These catalytic improvements translated into superior performance of the biocatalysts for the precipitation of calcium carbonate from solution which is an attractive strategy for long-term sequestration of captured carbon dioxide. Overall, these results demonstrate that synthetic biology approaches can be used to enhance heterogeneous catalysts incorporated into microbial whole-cell scaffolds.« less

Confined Mobility of TonB and FepA in Escherichia coli Membranes

PubMed Central

Lill, Yoriko; Jordan, Lorne D.; Smallwood, Chuck R.; Newton, Salete M.; Lill, Markus A.; Klebba, Phillip E.; Ritchie, Ken

2016-01-01

The important process of nutrient uptake in Escherichia coli, in many cases, involves transit of the nutrient through a class of beta-barrel proteins in the outer membrane known as TonB-dependent transporters (TBDTs) and requires interaction with the inner membrane protein TonB. Here we have imaged the mobility of the ferric enterobactin transporter FepA and TonB by tracking them in the membranes of live E. coli with single-molecule resolution at time-scales ranging from milliseconds to seconds. We employed simple simulations to model/analyze the lateral diffusion in the membranes of E.coli, to take into account both the highly curved geometry of the cell and artifactual effects expected due to finite exposure time imaging. We find that both molecules perform confined lateral diffusion in their respective membranes in the absence of ligand with FepA confined to a region 0.180−0.007+0.006 μm in radius in the outer membrane and TonB confined to a region 0.266−0.009+0.007 μm in radius in the inner membrane. The diffusion coefficient of these molecules on millisecond time-scales was estimated to be 21−5+9 μm2/s and 5.4−0.8+1.5 μm2/s for FepA and TonB, respectively, implying that each molecule is free to diffuse within its domain. Disruption of the inner membrane potential, deletion of ExbB/D from the inner membrane, presence of ligand or antibody to FepA and disruption of the MreB cytoskeleton was all found to further restrict the mobility of both molecules. Results are analyzed in terms of changes in confinement size and interactions between the two proteins. PMID:27935943

Confined Mobility of TonB and FepA in Escherichia coli Membranes.

PubMed

Lill, Yoriko; Jordan, Lorne D; Smallwood, Chuck R; Newton, Salete M; Lill, Markus A; Klebba, Phillip E; Ritchie, Ken

2016-01-01

The important process of nutrient uptake in Escherichia coli, in many cases, involves transit of the nutrient through a class of beta-barrel proteins in the outer membrane known as TonB-dependent transporters (TBDTs) and requires interaction with the inner membrane protein TonB. Here we have imaged the mobility of the ferric enterobactin transporter FepA and TonB by tracking them in the membranes of live E. coli with single-molecule resolution at time-scales ranging from milliseconds to seconds. We employed simple simulations to model/analyze the lateral diffusion in the membranes of E.coli, to take into account both the highly curved geometry of the cell and artifactual effects expected due to finite exposure time imaging. We find that both molecules perform confined lateral diffusion in their respective membranes in the absence of ligand with FepA confined to a region [Formula: see text] μm in radius in the outer membrane and TonB confined to a region [Formula: see text] μm in radius in the inner membrane. The diffusion coefficient of these molecules on millisecond time-scales was estimated to be [Formula: see text] μm2/s and [Formula: see text] μm2/s for FepA and TonB, respectively, implying that each molecule is free to diffuse within its domain. Disruption of the inner membrane potential, deletion of ExbB/D from the inner membrane, presence of ligand or antibody to FepA and disruption of the MreB cytoskeleton was all found to further restrict the mobility of both molecules. Results are analyzed in terms of changes in confinement size and interactions between the two proteins.

Proteomic analysis reveals novel extracellular virulence-associated proteins and functions regulated by the diffusible signal factor (DSF) in Xanthomonas oryzae pv. oryzicola.

PubMed

Qian, Guoliang; Zhou, Yijing; Zhao, Yancun; Song, Zhiwei; Wang, Suyan; Fan, Jiaqin; Hu, Baishi; Venturi, Vittorio; Liu, Fengquan

2013-07-05

Quorum sensing (QS) in Xanthomonas oryzae pv. oryzicola (Xoc), the causal agent of bacterial leaf streak, is mediated by the diffusible signal factor (DSF). DSF-mediating QS has been shown to control virulence and a set of virulence-related functions; however, the expression profiles and functions of extracellular proteins controlled by DSF signal remain largely unclear. In the present study, 33 DSF-regulated extracellular proteins, whose functions include small-protein mediating QS, oxidative adaptation, macromolecule metabolism, cell structure, biosynthesis of small molecules, intermediary metabolism, cellular process, protein catabolism, and hypothetical function, were identified by proteomics in Xoc. Of these, 15 protein encoding genes were in-frame deleted, and 4 of them, including three genes encoding type II secretion system (T2SS)-dependent proteins and one gene encoding an Ax21 (activator of XA21-mediated immunity)-like protein (a novel small-protein type QS signal) were determined to be required for full virulence in Xoc. The contributions of these four genes to important virulence-associated functions, including bacterial colonization, extracellular polysaccharide, cell motility, biofilm formation, and antioxidative ability, are presented. To our knowledge, our analysis is the first complete list of DSF-regulated extracellular proteins and functions in a Xanthomonas species. Our results show that DSF-type QS played critical roles in regulation of T2SS and Ax21-mediating QS, which sheds light on the role of DSF signaling in Xanthomonas.

Stochastic simulation of reaction-diffusion systems: A fluctuating-hydrodynamics approach

NASA Astrophysics Data System (ADS)

Kim, Changho; Nonaka, Andy; Bell, John B.; Garcia, Alejandro L.; Donev, Aleksandar

2017-03-01

We develop numerical methods for stochastic reaction-diffusion systems based on approaches used for fluctuating hydrodynamics (FHD). For hydrodynamic systems, the FHD formulation is formally described by stochastic partial differential equations (SPDEs). In the reaction-diffusion systems we consider, our model becomes similar to the reaction-diffusion master equation (RDME) description when our SPDEs are spatially discretized and reactions are modeled as a source term having Poisson fluctuations. However, unlike the RDME, which becomes prohibitively expensive for an increasing number of molecules, our FHD-based description naturally extends from the regime where fluctuations are strong, i.e., each mesoscopic cell has few (reactive) molecules, to regimes with moderate or weak fluctuations, and ultimately to the deterministic limit. By treating diffusion implicitly, we avoid the severe restriction on time step size that limits all methods based on explicit treatments of diffusion and construct numerical methods that are more efficient than RDME methods, without compromising accuracy. Guided by an analysis of the accuracy of the distribution of steady-state fluctuations for the linearized reaction-diffusion model, we construct several two-stage (predictor-corrector) schemes, where diffusion is treated using a stochastic Crank-Nicolson method, and reactions are handled by the stochastic simulation algorithm of Gillespie or a weakly second-order tau leaping method. We find that an implicit midpoint tau leaping scheme attains second-order weak accuracy in the linearized setting and gives an accurate and stable structure factor for a time step size of an order of magnitude larger than the hopping time scale of diffusing molecules. We study the numerical accuracy of our methods for the Schlögl reaction-diffusion model both in and out of thermodynamic equilibrium. We demonstrate and quantify the importance of thermodynamic fluctuations to the formation of a two-dimensional Turing-like pattern and examine the effect of fluctuations on three-dimensional chemical front propagation. By comparing stochastic simulations to deterministic reaction-diffusion simulations, we show that fluctuations accelerate pattern formation in spatially homogeneous systems and lead to a qualitatively different disordered pattern behind a traveling wave.

Stochastic simulation of reaction-diffusion systems: A fluctuating-hydrodynamics approach

DOE PAGES

Kim, Changho; Nonaka, Andy; Bell, John B.; ...

2017-03-24

Here, we develop numerical methods for stochastic reaction-diffusion systems based on approaches used for fluctuating hydrodynamics (FHD). For hydrodynamic systems, the FHD formulation is formally described by stochastic partial differential equations (SPDEs). In the reaction-diffusion systems we consider, our model becomes similar to the reaction-diffusion master equation (RDME) description when our SPDEs are spatially discretized and reactions are modeled as a source term having Poisson fluctuations. However, unlike the RDME, which becomes prohibitively expensive for an increasing number of molecules, our FHD-based description naturally extends from the regime where fluctuations are strong, i.e., each mesoscopic cell has few (reactive) molecules,more » to regimes with moderate or weak fluctuations, and ultimately to the deterministic limit. By treating diffusion implicitly, we avoid the severe restriction on time step size that limits all methods based on explicit treatments of diffusion and construct numerical methods that are more efficient than RDME methods, without compromising accuracy. Guided by an analysis of the accuracy of the distribution of steady-state fluctuations for the linearized reaction-diffusion model, we construct several two-stage (predictor-corrector) schemes, where diffusion is treated using a stochastic Crank-Nicolson method, and reactions are handled by the stochastic simulation algorithm of Gillespie or a weakly second-order tau leaping method. We find that an implicit midpoint tau leaping scheme attains second-order weak accuracy in the linearized setting and gives an accurate and stable structure factor for a time step size of an order of magnitude larger than the hopping time scale of diffusing molecules. We study the numerical accuracy of our methods for the Schlögl reaction-diffusion model both in and out of thermodynamic equilibrium. We demonstrate and quantify the importance of thermodynamic fluctuations to the formation of a two-dimensional Turing-like pattern and examine the effect of fluctuations on three-dimensional chemical front propagation. Furthermore, by comparing stochastic simulations to deterministic reaction-diffusion simulations, we show that fluctuations accelerate pattern formation in spatially homogeneous systems and lead to a qualitatively different disordered pattern behind a traveling wave.« less

Regenerated keratin membrane to match the in vitro drug diffusion through human epidermis

PubMed Central

Selmin, Francesca; Cilurzo, Francesco; Aluigi, Annalisa; Franzè, Silvia; Minghetti, Paola

2012-01-01

This work aimed to develop membranes made of regenerated keratin and ceramides (CERs) to match the barrier property of the human stratum corneum in in vitro percutaneous absorption studies. The membrane composition was optimized on the basis of the in vitro drug diffusion profiles of ibuprofen, propranolol and testosterone chosen as model drugs on the basis of their different diffusion and solubility properties. The data were compared to those obtained using human epidermis. The ATR-FTIR and SEM analyses revealed that CERs were suspended into the regenerated keratin matrix, even if a partial solubilization occurred. It resulted in the membranes being physically stable after exposure to aqueous buffer and/or mineral oil and the fluxes of ibuprofen and propranolol from these vehicles through membranes and human skin were of the same order of magnitude. The best relationship with human epidermis data was obtained with 180 μm-thick membrane containing 1% ceramide III and 1% ceramide VI. The data on the testosterone diffusion were affected by the exposure of the membrane to a water/ethanol solution over a prolonged period of time, indicating that such an organic solvent was able to modify the supermolecular organization of keratin and CERs. The keratin/CER membranes can represent a simplified model to assay the in vitro skin permeability study of small molecules. PMID:25755997

Core-based intrinsic fiber-optic absorption sensor for the detection of volatile organic compounds

NASA Astrophysics Data System (ADS)

Klunder, Gregory L.; Russo, Richard E.

1995-03-01

A core-based intrinsic fiber-optic absorption sensor has been developed and tested for the detection of volatile organic compounds. The distal ends of transmitting and receiving fibers are connected by a small cylindrical section of an optically clear silicone rubber. The silicone rubber acts both as a light pipe and as a selective membrane into which the analyte molecules can diffuse. The sensor has been used to detect volatile organics (trichloroethylene, 1,1-dichloroethylene, and benzene) in both aqueous solutions and in the vapor phase or headspace. Absorption spectra obtained in the near-infrared (near-IR) provide qualitative and quantitative information about the analyte. Water, which has strong broad-band absorption in the near-IR, is excluded from the spectra because of the hydrophobic properties of the silicone rubber. The rate-limiting step is shown to be the diffusion through the Nernstian boundary layer surrounding the sensor and not the diffusion through the silicone polymer. The rate of analyte diffusion into the sensor, as measured by the t(sub 90) values (the time required for the sensor to reach 90% of the equilibrium value), is 30 min for measurements in aqueous solutions and approximately 3 min for measurements made in the headspace. The limit of detection obtained with this sensor is approximately 1.1 ppm for trichloroethylene in an aqueous solution.

Bayesian framework for modeling diffusion processes with nonlinear drift based on nonlinear and incomplete observations.

PubMed

Wu, Hao; Noé, Frank

2011-03-01

Diffusion processes are relevant for a variety of phenomena in the natural sciences, including diffusion of cells or biomolecules within cells, diffusion of molecules on a membrane or surface, and diffusion of a molecular conformation within a complex energy landscape. Many experimental tools exist now to track such diffusive motions in single cells or molecules, including high-resolution light microscopy, optical tweezers, fluorescence quenching, and Förster resonance energy transfer (FRET). Experimental observations are most often indirect and incomplete: (1) They do not directly reveal the potential or diffusion constants that govern the diffusion process, (2) they have limited time and space resolution, and (3) the highest-resolution experiments do not track the motion directly but rather probe it stochastically by recording single events, such as photons, whose properties depend on the state of the system under investigation. Here, we propose a general Bayesian framework to model diffusion processes with nonlinear drift based on incomplete observations as generated by various types of experiments. A maximum penalized likelihood estimator is given as well as a Gibbs sampling method that allows to estimate the trajectories that have caused the measurement, the nonlinear drift or potential function and the noise or diffusion matrices, as well as uncertainty estimates of these properties. The approach is illustrated on numerical simulations of FRET experiments where it is shown that trajectories, potentials, and diffusion constants can be efficiently and reliably estimated even in cases with little statistics or nonequilibrium measurement conditions.

Coarse-grained molecular dynamics simulation of water diffusion in the presence of carbon nanotubes.

PubMed

Lado Touriño, Isabel; Naranjo, Arisbel Cerpa; Negri, Viviana; Cerdán, Sebastián; Ballesteros, Paloma

2015-11-01

Computational modeling of the translational diffusion of water molecules in anisotropic environments entails vital relevance to understand correctly the information contained in the magnetic resonance images weighted in diffusion (DWI) and of the diffusion tensor images (DTI). In the present work we investigated the validity, strengths and weaknesses of a coarse-grained (CG) model based on the MARTINI force field to simulate water diffusion in a medium containing carbon nanotubes (CNTs) as models of anisotropic water diffusion behavior. We show that water diffusion outside the nanotubes follows Ficḱs law, while water diffusion inside the nanotubes is not described by a Ficḱs behavior. We report on the influence on water diffusion of various parameters such as length and concentration of CNTs, comparing the CG results with those obtained from the more accurate classic force field calculation, like the all-atom approach. Calculated water diffusion coefficients decreased in the presence of nanotubes in a concentration dependent manner. We also observed smaller water diffusion coefficients for longer CNTs. Using the CG methodology we were able to demonstrate anisotropic diffusion of water inside the nanotube scaffold, but we could not prove anisotropy in the surrounding medium, suggesting that grouping several water molecules in a single diffusing unit may affect the diffusional anisotropy calculated. The methodologies investigated in this work represent a first step towards the study of more complex models, including anisotropic cohorts of CNTs or even neuronal axons, with reasonable savings in computation time. Copyright © 2015 Elsevier Inc. All rights reserved.

Microgravity

NASA Image and Video Library

2001-01-24

This photo shows the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells (inside the plastic box) will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

Microgravity

NASA Image and Video Library

2001-01-24

This photo shows an individual cell from the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

Determination of the equilibrium constant of C60 fullerene binding with drug molecules.

PubMed

Mosunov, Andrei A; Pashkova, Irina S; Sidorova, Maria; Pronozin, Artem; Lantushenko, Anastasia O; Prylutskyy, Yuriy I; Parkinson, John A; Evstigneev, Maxim P

2017-03-01

We report a new analytical method that allows the determination of the magnitude of the equilibrium constant of complexation, K h , of small molecules to C 60 fullerene in aqueous solution. The developed method is based on the up-scaled model of C 60 fullerene-ligand complexation and contains the full set of equations needed to fit titration datasets arising from different experimental methods (UV-Vis spectroscopy, 1 H NMR spectroscopy, diffusion ordered NMR spectroscopy, DLS). The up-scaled model takes into consideration the specificity of C 60 fullerene aggregation in aqueous solution and allows the highly dispersed nature of C 60 fullerene cluster distribution to be accounted for. It also takes into consideration the complexity of fullerene-ligand dynamic equilibrium in solution, formed by various types of self- and hetero-complexes. These features make the suggested method superior to standard Langmuir-type analysis, the approach used to date for obtaining quantitative information on ligand binding with different nanoparticles.

Influence of hot and cold neutrals on scrape-off layer tokamak plasma turbulence

NASA Astrophysics Data System (ADS)

Bisai, N.; Kaw, P. K.

2018-01-01

The modification of interchange plasma turbulence in the scrape-off layer (SOL) region by the presence of hot and cold neutral gas molecules has been studied. The nonlinear equations have been solved numerically using two different simulations ("uniform-Te" and "varying-Te"), and the results obtained from both of the models have been compared. The hot neutrals, responsible for the increase in the electron density in the SOL, also account for more ionization of the cold molecules. The effect of hot and cold neutrals on the interchange turbulence is almost similar in the "uniform-Te" model, but in the "varying-Te" model, the influence of the hot neutrals is very small, specifically in the far SOL region. The neutral gas in the "varying Te" model decreases the heat load on the material walls by about 7%. A reduction in the radial velocity by about 25% and effective diffusion coefficient of the plasma particles has been found by the influence of the neutral gas.

Dynamics in the Plastic Crystalline Phases of Cyclohexanol and Cyclooctanol Studied by Quasielastic Neutron Scattering.

PubMed

Novak, E; Jalarvo, N; Gupta, S; Hong, K; Förster, S; Egami, T; Ohl, M

2018-06-01

Plastic crystals are a promising candidate for solid state ionic conductors. In this work, quasielastic neutron scattering is employed to investigate the center of mass diffusive motions in two types of plastic crystalline cyclic alcohols: cyclohexanol and cyclooctanol. Two separate motions are observed which are attributed to long-range translational diffusion (α-process) and cage rattling (fast β-process). Residence times and diffusion coefficients are calculated for both processes, along with the confinement distances for the cage rattling. In addition, a binary mixture of these two materials is measured to understand how the dynamics change when a second type of molecule is added to the matrix. It is observed that, upon the addition of the larger cyclooctanol molecules into the cyclohexanol solution, the cage size decreases, which causes a decrease in the observed diffusion rates for both the α- and fast β-processes.

Unveiling the Interplay Between Diffusing CO2 and Ethanol Molecules in Champagne Wines by Classical Molecular Dynamics and (13)C NMR Spectroscopy.

PubMed

Bonhommeau, David A; Perret, Alexandre; Nuzillard, Jean-Marc; Cilindre, Clara; Cours, Thibaud; Alijah, Alexander; Liger-Belair, Gérard

2014-12-18

The diffusion coefficients of carbon dioxide (CO2) and ethanol (EtOH) in carbonated hydroalcoholic solutions and Champagne wines are evaluated as a function of temperature by classical molecular dynamics (MD) simulations and (13)C NMR spectroscopy measurements. The excellent agreement between theoretical and experimental diffusion coefficients suggest that ethanol is the main molecule, apart from water, responsible for the value of the CO2 diffusion coefficients in typical Champagne wines, a result that could likely be extended to most sparkling wines with alike ethanol concentrations. CO2 and EtOH hydrodynamical radii deduced from viscometry measurements by applying the Stokes-Einstein relationship are found to be mostly constant and in close agreement with MD predictions. The reliability of our approach should be of interest to physical chemists aiming to model transport phenomena in supersaturated aqueous solutions or water/alcohol mixtures.

Diffusion engineering of ions and charge carriers for stable efficient perovskite solar cells

NASA Astrophysics Data System (ADS)

Bi, Enbing; Chen, Han; Xie, Fengxian; Wu, Yongzhen; Chen, Wei; Su, Yanjie; Islam, Ashraful; Grätzel, Michael; Yang, Xudong; Han, Liyuan

2017-06-01

Long-term stability is crucial for the future application of perovskite solar cells, a promising low-cost photovoltaic technology that has rapidly advanced in the recent years. Here, we designed a nanostructured carbon layer to suppress the diffusion of ions/molecules within perovskite solar cells, an important degradation process in the device. Furthermore, this nanocarbon layer benefited the diffusion of electron charge carriers to enable a high-energy conversion efficiency. Finally, the efficiency on a perovskite solar cell with an aperture area of 1.02 cm2, after a thermal aging test at 85 °C for over 500 h, or light soaking for 1,000 h, was stable of over 15% during the entire test. The present diffusion engineering of ions/molecules and photo generated charges paves a way to realizing long-term stable and highly efficient perovskite solar cells.

Comparing Vibrationally Averaged Nuclear Shielding Constants by Quantum Diffusion Monte Carlo and Second-Order Perturbation Theory.

PubMed

Ng, Yee-Hong; Bettens, Ryan P A

2016-03-03

Using the method of modified Shepard's interpolation to construct potential energy surfaces of the H2O, O3, and HCOOH molecules, we compute vibrationally averaged isotropic nuclear shielding constants ⟨σ⟩ of the three molecules via quantum diffusion Monte Carlo (QDMC). The QDMC results are compared to that of second-order perturbation theory (PT), to see if second-order PT is adequate for obtaining accurate values of nuclear shielding constants of molecules with large amplitude motions. ⟨σ⟩ computed by the two approaches differ for the hydrogens and carbonyl oxygen of HCOOH, suggesting that for certain molecules such as HCOOH where big displacements away from equilibrium happen (internal OH rotation), ⟨σ⟩ of experimental quality may only be obtainable with the use of more sophisticated and accurate methods, such as quantum diffusion Monte Carlo. The approach of modified Shepard's interpolation is also extended to construct shielding constants σ surfaces of the three molecules. By using a σ surface with the equilibrium geometry as a single data point to compute isotropic nuclear shielding constants for each descendant in the QDMC ensemble representing the ground state wave function, we reproduce the results obtained through ab initio computed σ to within statistical noise. Development of such an approach could thereby alleviate the need for any future costly ab initio σ calculations.

Hybrid approaches for multiple-species stochastic reaction-diffusion models

NASA Astrophysics Data System (ADS)

Spill, Fabian; Guerrero, Pilar; Alarcon, Tomas; Maini, Philip K.; Byrne, Helen

2015-10-01

Reaction-diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction-diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model.

Hybrid approaches for multiple-species stochastic reaction-diffusion models.

PubMed

Spill, Fabian; Guerrero, Pilar; Alarcon, Tomas; Maini, Philip K; Byrne, Helen

2015-10-15

Reaction-diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction-diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model.

Hybrid approaches for multiple-species stochastic reaction–diffusion models

PubMed Central

Spill, Fabian; Guerrero, Pilar; Alarcon, Tomas; Maini, Philip K.; Byrne, Helen

2015-01-01

Reaction–diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction–diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model. PMID:26478601

Intercellular and intracellular signalling systems that globally control the expression of virulence genes in plant pathogenic bacteria.

PubMed

Ham, Jong Hyun

2013-04-01

Plant pathogenic bacteria utilize complex signalling systems to control the expression of virulence genes at the cellular level and within populations. Quorum sensing (QS), an important intercellular communication mechanism, is mediated by different types of small molecules, including N-acyl homoserine lactones (AHLs), fatty acids and small proteins. AHL-mediated signalling systems dependent on the LuxI and LuxR family proteins play critical roles in the virulence of a wide range of Gram-negative plant pathogenic bacteria belonging to the Alphaproteobacteria, Betaproteobacteria and Gammaproteobacteria. Xanthomonas spp. and Xylella fastidiosa, members of the Gammaproteobacteria, however, possess QS systems that are mediated by fatty acid-type diffusible signal factors (DSFs). Recent studies have demonstrated that Ax21, a 194-amino-acid protein in Xanthomonas oryzae pv. oryzae, plays dual functions in activating a rice innate immune pathway through binding to the rice XA21 pattern recognition receptor and in regulating bacterial virulence and biofilm formation as a QS signal molecule. In xanthomonads, DSF-mediated QS systems are connected with the signalling pathways mediated by cyclic diguanosine monophosphate (c-di-GMP), which functions as a second messenger for the control of virulence gene expression in these bacterial pathogens. © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

Small molecule chemical probes of microRNA function.

PubMed

Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R; Disney, Matthew D

2015-02-01

MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as progress is made in understanding small molecule recognition of RNA. Copyright © 2014. Published by Elsevier Ltd.

Single-molecule fluorescence study of the inhibition of the oncogenic functionality of STAT3

NASA Astrophysics Data System (ADS)

Liu, Baoxu; Badali, Daniel; Fletcher, Steven; Avadisian, Miriam; Gunning, Patrick; Gradinaru, Claudiu

2009-06-01

Signal-Transducer-and-Activator-of-Transcription 3 (STAT3) protein plays an important role in the onset of cancers such as leukemia and lymphoma. In this study, we aim to test the effectiveness of a novel peptide drug designed to tether STAT3 to the phospholipid bilayer of the cell membrane and thus inhibit unwanted transcription. As a first step, STAT3 proteins were successfully labelled with tetramethylrhodamine (TMR), a fluorescent dye with suitable photostability for single molecule studies. The effectiveness of labelling was determined using fluorescence correlation spectroscopy in a custom built confocal microscope, from which diffusion times and hydrodynamic radii of individual proteins were determined. A newly developed fluorescein derivative label (F-NAc) has been designed to be incorporated into the structure of the peptide drug so that peptide-STAT3 interactions can be examined. This dye is spectrally characterized and is found to be well suited for its application to this project, as well as other single-molecule studies. The membrane localization via high-affinity cholesterol-bound small-molecule binding agents can be demonstrated by encapsulating TMR-labeled STAT3 and inhibitors within a vesicle model cell system. To this end, unilaminar lipid vesicles were examined for size and encapsulation ability. Preliminary results of the efficiency and stability of the STAT3 anchoring in lipid membranes obtained via quantitative confocal imaging and single-molecule spectroscopy using a custom-built multiparameter fluorescence microscope are reported here.

Isolated effects of external bath osmolality, solute concentration, and electrical charge on solute transport across articular cartilage.

PubMed

Pouran, Behdad; Arbabi, Vahid; Zadpoor, Amir A; Weinans, Harrie

2016-12-01

The metabolic function of cartilage primarily depends on transport of solutes through diffusion mechanism. In the current study, we use contrast enhanced micro-computed tomography to determine equilibrium concentration of solutes through different cartilage zones and solute flux in the cartilage, using osteochondral plugs from equine femoral condyles. Diffusion experiments were performed with two solutes of different charge and approximately equal molecular weight, namely iodixanol (neutral) and ioxaglate (charge=-1) in order to isolate the effects of solute's charge on diffusion. Furthermore, solute concentrations as well as bath osmolality were changed to isolate the effects of steric hindrance on diffusion. Bath concentration and bath osmolality only had minor effects on the diffusion of the neutral solute through cartilage at the surface, middle and deep zones, indicating that the diffusion of the neutral solute was mainly Fickian. The negatively charged solute diffused considerably slower through cartilage than the neutral solute, indicating a large non-Fickian contribution in the diffusion of charged molecules. The numerical models determined maximum solute flux in the superficial zone up to a factor of 2.5 lower for the negatively charged solutes (charge=-1) as compared to the neutral solutes confirming the importance of charge-matrix interaction in diffusion of molecules across cartilage. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Modes of Diffusion of Cholera Toxin Bound to GM1 on Live Cell Membrane by Image Mean Square Displacement Analysis

PubMed Central

Moens, Pierre D.J.; Digman, Michelle A.; Gratton, Enrico

2015-01-01

The image-mean square displacement technique applies the calculation of the mean square displacement commonly used in single-molecule tracking to images without resolving single particles. The image-mean square displacement plot obtained is similar to the mean square displacement plot obtained using the single-particle tracking technique. This plot is then used to reconstruct the protein diffusion law and to identify whether the labeled molecules are undergoing pure isotropic, restricted, corralled, transiently confined, or directed diffusion. In our study total internal reflection fluorescence microscopy images were taken of Cholera toxin subunit B (CtxB) membrane-labeled NIH 3T3 mouse fibroblasts and MDA 231 MB cells. We found a population of CTxB undergoing purely isotropic diffusion and one displaying restricted diffusion with corral sizes ranging from 150 to ∼1800 nm. We show that the diffusion rate of CTxB bound to GM1 is independent of the size of the confinement, suggesting that the mechanism of confinement is different from the mechanism controlling the diffusion rate of CtxB. We highlight the potential effect of continuous illumination on the diffusion mode of CTxB. We also show that aggregation of CTxB/GM1 in large complexes occurs and that these aggregates tend to have slower diffusion rates. PMID:25809257

Modes of diffusion of cholera toxin bound to GM1 on live cell membrane by image mean square displacement analysis.

PubMed

Moens, Pierre D J; Digman, Michelle A; Gratton, Enrico

2015-03-24

The image-mean square displacement technique applies the calculation of the mean square displacement commonly used in single-molecule tracking to images without resolving single particles. The image-mean square displacement plot obtained is similar to the mean square displacement plot obtained using the single-particle tracking technique. This plot is then used to reconstruct the protein diffusion law and to identify whether the labeled molecules are undergoing pure isotropic, restricted, corralled, transiently confined, or directed diffusion. In our study total internal reflection fluorescence microscopy images were taken of Cholera toxin subunit B (CtxB) membrane-labeled NIH 3T3 mouse fibroblasts and MDA 231 MB cells. We found a population of CTxB undergoing purely isotropic diffusion and one displaying restricted diffusion with corral sizes ranging from 150 to ∼1800 nm. We show that the diffusion rate of CTxB bound to GM1 is independent of the size of the confinement, suggesting that the mechanism of confinement is different from the mechanism controlling the diffusion rate of CtxB. We highlight the potential effect of continuous illumination on the diffusion mode of CTxB. We also show that aggregation of CTxB/GM1 in large complexes occurs and that these aggregates tend to have slower diffusion rates. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

Shin, Heekeun; Schwarze, A; Diehl, R D

Earlier studies of C60 adsorption on Au(111) reported many interesting and complex features. We have performed coordinated low-energy electron diffraction, scanning tunneling microscopy (STM), and density functional theory studies to elucidate some of the details of the monolayer commensurate (2√3 × 2√3)R30° phase. We have identified the adsorption geometries of the two states that image as dim and bright in STM. These consist of a C60 molecule with a hexagon side down in a vacancy (hex-vac) and a C60 molecule with a carbon-carbon 6:6 bond down on a top site (6:6-top), respectively. We have studied the detailed geometries of thesemore » states and find that there is little distortion of the C60 molecules, but there is a rearrangement of the substrate near the C60 molecules. The two types of molecules differ in height, by about 0.7 Å, which accounts for most of the difference in their contrast in the STM images. The monolayer displays dynamical behavior, in which the molecules flip from bright to dim, and vice versa. We interpret this flipping as the result of the diffusion of vacancies in the surface layers of the substrate. Our measurements of the dynamics of this flipping from one state to the other indicate that the activation energy is 0.66 ± 0.03 eV for flips that involve nearest-neighbor C60 molecules, and 0.93 ± 0.03 for more distant flips. Based on calculated activation energies for vacancies diffusing in Au, we interpret these to be a result of surface vacancy diffusion and bulk vacancy diffusion. These results are compared to the similar system of Ag(111)-(2√3 × 2√3)R30°-C60. In both systems, the formation of the commensurate C60 monolayer produces a large number of vacancies in the top substrate layer that are highly mobile, effectively melting the interfacial metal layer at temperatures well below their normal melting temperatures.« less

CURVATURE-DRIVEN MOLECULAR FLOW ON MEMBRANE SURFACE*

PubMed Central

MIKUCKI, MICHAEL; ZHOU, Y. C.

2017-01-01

This work presents a mathematical model for the localization of multiple species of diffusion molecules on membrane surfaces. Morphological change of bilayer membrane in vivo is generally modulated by proteins. Most of these modulations are associated with the localization of related proteins in the crowded lipid environments. We start with the energetic description of the distributions of molecules on curved membrane surface, and define the spontaneous curvature of bilayer membrane as a function of the molecule concentrations on membrane surfaces. A drift-diffusion equation governs the gradient flow of the surface molecule concentrations. We recast the energetic formulation and the related governing equations by using an Eulerian phase field description to define membrane morphology. Computational simulations with the proposed mathematical model and related numerical techniques predict (i) the molecular localization on static membrane surfaces at locations with preferred mean curvatures, and (ii) the generation of preferred mean curvature which in turn drives the molecular localization. PMID:29056778

Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA.

PubMed

Velagapudi, Sai Pradeep; Luo, Yiling; Tran, Tuan; Haniff, Hafeez S; Nakai, Yoshio; Fallahi, Mohammad; Martinez, Gustavo J; Childs-Disney, Jessica L; Disney, Matthew D

2017-03-22

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs.

Photon Antibunching in the Fluorescence of a Single Dye Molecule Trapped in a Solid

DTIC Science & Technology

1992-06-08

number) FIELD GROUP SUB-GROUP single-molecule spectroscopy in solids, photon antibunching, quantum-optics, nonclassical effects pentacene in p-terphenyl...emitted by an optically pumped single molecule of pentacene In a p-terphenyl host has been Investigated at short times. The correlation function...excitation tcclnique, certain individual pentacene impurity molecules in a p-terphenyl crystal 11 were observed to spectrally diffuse, i.e. their absorption