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Sample records for molecular motor kif3

  1. Properties of the Kinesin-1 motor DdKif3 from Dictyostelium discoideum.

    PubMed

    Röhlk, Christian; Rohlfs, Meino; Leier, Sven; Schliwa, Manfred; Liu, Xiao; Parsch, John; Woehlke, Günther

    2008-04-01

    The amoeba Dictyostelium discoideum possesses genes for 13 different kinesins. Here we characterize DdKif3, a member of the Kinesin-1 family. Kinesin-1 motors form homodimers that can move micrometer-long distances on microtubules using the energy derived from ATP hydrolysis. We expressed recombinant motors in Escherichia coli and tested them in different in vitro assays. Full-length and truncated Kif3 motors were active in gliding and ATPase assays. They showed a strong dependence on ionic strength. Like the full-length motor, the truncated DdKif3-592 motor (aa 1-592; comprising motor domain, neck, and partial stalk) reached its maximum speed of around 2.0micrcom s(-1) at a potassium acetate concentration of 200mM. The shortened DdKif3-342 motor (aa 1-342; comprising motor domain, partial neck) showed a high ATP turnover, comparable to that of the fungal Kinesin-1, Nkin. Results from the duty cycle calculations and gliding assays indicate that DdKif3 is a processive motor. A GFP-fusion protein revealed a mainly cytoplasmic localization of DdKif3. Immunofluorescence staining makes an association with the endoplasmic reticulum or mitochondria unlikely. Despite a similar phylogenetic distance to both metazoa and fungi, in terms of its biochemical properties DdKif3 revealed a closer similarity to fungal than animal kinesins.

  2. Molecular characterization of a KIF3B-like kinesin gene in the testis of Octopus tankahkeei (Cephalopoda, Octopus).

    PubMed

    Dang, Ran; Zhu, Jun-Quan; Tan, Fu-Qing; Wang, Wei; Zhou, Hong; Yang, Wan-Xi

    2012-05-01

    KIF3B is known for maintaining and assembling cilia and flagellum. To date, the function of KIF3B and its relationship with KIF3A during spermiogenesis in the cephalopod Octopus tankahkeei remains unknown. In the present study, we characterized a gene encoding a homologue of rat KIF3B in the O. tankahkeei testis and examined its temporal and spatial expression pattern during spermiogenesis. The cDNA of KIF3B was obtained with degenerate and RACE PCR and the distribution pattern of ot-kif3b were observed with RT-PCR. The morphological development during spermiogenesis was illustrated by histological and transmission electron microscopy and mRNA expression of ot-kif3b was observed by in situ hybridization. The 2,365 nucleotides cDNA consisted of a 102 bp 5' untranslated region (UTR), a 2,208 bp open reading frame (ORF) encoding a protein of 736 amino acids, and a 55 bp 3' UTR. Multiple alignments revealed that the putative Ot-KIF3B shared 68, 68, 69, 68, and 67% identity with that of Homo sapiens, Mus musculus, Gallus gallus, Danio rerio, and Xenopus laevis, respectively, along with high identities with Ot-KIF3A in fundamental structures. Ot-kif3b transcripts appeared gradually in early spermatids, increased in intermediate spermatids and maximized in drastically remodeled and final spermatids. The kif3b gene is identified and its expression pattern is demonstrated for the first time in O. tankahkeei. Compared to ot-kif3a reported by our laboratory before, our data suggested that the putative heterodimeric motor proteins Ot-KIF3A/B may be involved in intraspermatic transport and might contribute to structural changes during spermiogenesis.

  3. Kinesin-2 KIF3AC and KIF3AB Can Drive Long-Range Transport along Microtubules

    PubMed Central

    Guzik-Lendrum, Stephanie; Rank, Katherine C.; Bensel, Brandon M.; Taylor, Keenan C.; Rayment, Ivan; Gilbert, Susan P.

    2015-01-01

    Mammalian KIF3AC is classified as a heterotrimeric kinesin-2 that is best known for organelle transport in neurons, yet in vitro studies to characterize its single molecule behavior are lacking. The results presented show that a KIF3AC motor that includes the native helix α7 sequence for coiled-coil formation is highly processive with run lengths of ∼1.23 μm and matching those exhibited by conventional kinesin-1. This result was unexpected because KIF3AC exhibits the canonical kinesin-2 neck-linker sequence that has been reported to be responsible for shorter run lengths observed for another heterotrimeric kinesin-2, KIF3AB. However, KIF3AB with its native neck linker and helix α7 is also highly processive with run lengths of ∼1.62 μm and exceeding those of KIF3AC and kinesin-1. Loop L11, a component of the microtubule-motor interface and implicated in activating ADP release upon microtubule collision, is significantly extended in KIF3C as compared with other kinesins. A KIF3AC encoding a truncation in KIF3C loop L11 (KIF3ACΔL11) exhibited longer run lengths at ∼1.55 μm than wild-type KIF3AC and were more similar to KIF3AB run lengths, suggesting that L11 also contributes to tuning motor processivity. The steady-state ATPase results show that shortening L11 does not alter kcat, consistent with the observation that single molecule velocities are not affected by this truncation. However, shortening loop L11 of KIF3C significantly increases the microtubule affinity of KIF3ACΔL11, revealing another structural and mechanistic property that can modulate processivity. The results presented provide new, to our knowledge, insights to understand structure-function relationships governing processivity and a better understanding of the potential of KIF3AC for long-distance transport in neurons. PMID:26445448

  4. Disruption of KIF3A in patient-derived glioblastoma cells: effects on ciliogenesis, hedgehog sensitivity, and tumorigenesis

    PubMed Central

    Hoang-Minh, Lan B.; Deleyrolle, Loic P.; Siebzehnrubl, Dorit; Ugartemendia, George; Futch, Hunter; Griffith, Benjamin; Breunig, Joshua J.; De Leon, Gabriel; Mitchell, Duane A.; Semple-Rowland, Susan; Reynolds, Brent A.; Sarkisian, Matthew R.

    2016-01-01

    KIF3A, a component of the kinesin-2 motor, is necessary for the progression of diverse tumor types. This is partly due to its role in regulating ciliogenesis and cell responsiveness to sonic hedgehog (SHH). Notably, primary cilia have been detected in human glioblastoma multiforme (GBM) tumor biopsies and derived cell lines. Here, we asked whether disrupting KIF3A in GBM cells affected ciliogenesis, in vitro growth and responsiveness to SHH, or tumorigenic behavior in vivo. We used a lentiviral vector to create three patient-derived GBM cell lines expressing a dominant negative, motorless form of Kif3a (dnKif3a). In all unmodified lines, we found that most GBM cells were capable of producing ciliated progeny and that dnKif3a expression in these cells ablated ciliogenesis. Interestingly, unmodified and dnKif3a-expressing cell lines displayed differential sensitivities and pathway activation to SHH and variable tumor-associated survival following mouse xenografts. In one cell line, SHH-induced cell proliferation was prevented in vitro by either expressing dnKif3a or inhibiting SMO signaling using cyclopamine, and the survival times of mice implanted with dnKif3a-expressing cells were increased. In a second line, expression of dnKif3a increased the cells' baseline proliferation while, surprisingly, sensitizing them to SHH-induced cell death. The survival times of mice implanted with these dnKif3a-expressing cells were decreased. Finally, expression of dnKif3a in a third cell line had no effect on cell proliferation, SHH sensitivity, or mouse survival times. These findings indicate that KIF3A is essential for GBM cell ciliogenesis, but its role in modulating GBM cell behavior is highly variable. PMID:26760767

  5. Disruption of KIF3A in patient-derived glioblastoma cells: effects on ciliogenesis, hedgehog sensitivity, and tumorigenesis.

    PubMed

    Hoang-Minh, Lan B; Deleyrolle, Loic P; Siebzehnrubl, Dorit; Ugartemendia, George; Futch, Hunter; Griffith, Benjamin; Breunig, Joshua J; De Leon, Gabriel; Mitchell, Duane A; Semple-Rowland, Susan; Reynolds, Brent A; Sarkisian, Matthew R

    2016-02-09

    KIF3A, a component of the kinesin-2 motor, is necessary for the progression of diverse tumor types. This is partly due to its role in regulating ciliogenesis and cell responsiveness to sonic hedgehog (SHH). Notably, primary cilia have been detected in human glioblastoma multiforme (GBM) tumor biopsies and derived cell lines. Here, we asked whether disrupting KIF3A in GBM cells affected ciliogenesis, in vitro growth and responsiveness to SHH, or tumorigenic behavior in vivo. We used a lentiviral vector to create three patient-derived GBM cell lines expressing a dominant negative, motorless form of Kif3a (dnKif3a). In all unmodified lines, we found that most GBM cells were capable of producing ciliated progeny and that dnKif3a expression in these cells ablated ciliogenesis. Interestingly, unmodified and dnKif3a-expressing cell lines displayed differential sensitivities and pathway activation to SHH and variable tumor-associated survival following mouse xenografts. In one cell line, SHH-induced cell proliferation was prevented in vitro by either expressing dnKif3a or inhibiting SMO signaling using cyclopamine, and the survival times of mice implanted with dnKif3a-expressing cells were increased. In a second line, expression of dnKif3a increased the cells' baseline proliferation while, surprisingly, sensitizing them to SHH-induced cell death. The survival times of mice implanted with these dnKif3a-expressing cells were decreased. Finally, expression of dnKif3a in a third cell line had no effect on cell proliferation, SHH sensitivity, or mouse survival times. These findings indicate that KIF3A is essential for GBM cell ciliogenesis, but its role in modulating GBM cell behavior is highly variable.

  6. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    SciTech Connect

    Duangtum, Natapol; Junking, Mutita; Sawasdee, Nunghathai; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2011-09-16

    Highlights: {yields} Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). {yields} The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. {yields} The co-localization between kAE and KIF3B was detected in human kidney tissues. {yields} A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. {yields} KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of {alpha}-intercalated cells of the kidney collecting duct leads to the defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange and the failure of proton (H{sup +}) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney {alpha}-intercalated cells.

  7. Molecular motors

    NASA Astrophysics Data System (ADS)

    Allemand, Jean François Desbiolles, Pierre

    2015-10-01

    How do we move? More precisely, what are the molecular mechanisms that can explain that our muscles, made of very small components can move at a osopic scale? To answer these questions we must introduce molecular motors. Those motors are proteins, or small protein assemblies that, in our cells, transform chemical energy into mechanical work. Then, like we could do for a oscopic motor, used in a car or in a fan, we are going to study the basic behavior of these molecular machines, present what are their energy sources, calculate their power, their yield. If molecular motors are crucial for our oscopic movements, we are going to see that they are also essential to cellular transport and that considering the activity of some enzymes as molecular motors bring some interesting new insights on their activity.

  8. CB-08KIF3A IS ESSENTIAL FOR CILIOGENESIS, CILIA FUNCTION AND PROMOTES GLIOBLASTOMA PROGRESSION

    PubMed Central

    Hoang-Minh, Lan; Deleyrolle, Loic; Ugartemendia, George; Breunig, Joshua; Semple-Rowland, Susan; Reynolds, Brent; Sarkisian, Matthew

    2014-01-01

    Despite recent findings that cilia transduce diverse signaling pathways affecting cell proliferation, migration and survival, little is known about the influence of cilia or cilia-associated proteins in glioblastoma multiforme (GBM). We recently showed that primary cilia project from subsets of cells in GBM patient biopsies and derived cell lines. To determine if cilia contribute to GBM growth, we blocked ciliogenesis using a lentivirus expressing a dominant negative form of KIF3A, an essential ciliogenesis protein. We generated stable GBM cell lines (L0 and S3; representing different molecular subclasses) whereby dnKIF3A+ cells exhibited virtual complete loss of cilia compared to controls (confirmed by immunostaining and EM). Canonically, secreted Sonic hedgehog (SHH) ligand binds and activates receptor signaling cascades (e.g., smoothened (SMO)) within cilia to promote normal cell proliferation and tumor cell growth in specific developmental and pathological contexts, respectively. To examine the role of SHH in GBM proliferation, we exposed control and dnKIF3A+ L0 and S3 cells to saline or recombinant SHH. We found the number of L0 control cells significantly increased after SHH compared to saline, an effect blocked by pretreatment with cyclopamine (SMO inhibitor). However, SHH did not increase the number of L0 dnKIF3A+ cells. Interestingly, SHH exposure had no effect on S3 control cell numbers, despite observations that SHH signaling components (SMO and Gli3) were recruited to their cilia in response to SHH. This suggests GBM cilia are SHH-responsive but the downstream consequences of ciliary signaling may differ between cell lines. Notably, mice intracranially xenografted with L0 cells expressing dnKIF3A survived significantly longer than mice receiving control cells, and retained the loss of cilia phenotype in the tumors. Collectively, these data suggest KIF3A promotes GBM tumor progression, but the extent to which the effects are mediated by cilia and the

  9. Disruption of kif3a results in defective osteoblastic differentiation in dental mesenchymal stem/precursor cells via the Wnt signaling pathway

    PubMed Central

    Jiang, Sicong; Chen, Guoqing; Feng, Lian; Jiang, Zongting; Yu, Mei; Bao, Jinku; Tian, Weidong

    2016-01-01

    The anterograde intraflagellar transport motor protein, kif3a, regulates the integrity of primary cilia and various cellular functions, however, the role of kif3a in dental mesenchymal stem/precursor cell differentiation remains to be fully elucidated. In the present study, the expression of kif3a was knocked down in human dental follicle cells (hDFCs) and human dental pulp cells (hDPCs) using short hairpin RNA. The results of subsequent immunofluorescence revealed that knocking down kif3a resulted in the loss of primary cilia, which led to impairment of substantial mineralization and expression of the differentiation-associated markers, including alkaline phosphatase, Runt-related transcription factor 2, dentin matrix protein 1 and dentin sialophosphoprotein in the hDFCs and hDPCs. The results of reverse transcription-quantitative polymerase chain reaction and western blot analyses showed that the expression levels of Wnt3a-mediated active β-catenin and lymphoid enhancer-binding factor 1 were attenuated, whereas the expression of phosphorylated glycogen synthase kinase 3β was enhanced, in the kif3a-knockdown cells. In addition, exogenous Wnt3a partially rescued osteoblastic differentiation in the hDFCs and hDPCs. These results demonstrated that inhibition of kif3a in the hDFCs and hDPCs disrupted primary cilia formation and/or function, and indicated that kif3a is important in the differentiation of hDFCs and hDPCs through the Wnt pathway. These findings not only enhance current understanding of tooth development and diseases of tooth mineralization, but also indicate possible strategies to regulate mineralization during tooth repair and regeneration. PMID:27432616

  10. Molecular Motors from DNA

    NASA Astrophysics Data System (ADS)

    Turberfield, Andrew

    2013-03-01

    DNA is a wonderful material for nanoscale construction: its self-assembly can be programmed by making use of its information-carrying capability and its hybridization or hydrolysis can be used as to provide energy for synthetic molecular machinery. With DNA it is possible to design and build three-dimensional scaffolds, to attach molecular components to them with sub-nanometre precision-and then to make them move. I shall describe our work on autonomous, biomimetic molecular motors powered by chemical fuels and the use of synthetic molecular machinery to control covalent chemical synthesis. I shall demonstrate bipedal motors whose operation depends on the coordination of the chemomechanical cycles of two separate catalytic centres and burnt bridges motors that can be programmed to navigate networks of tracks. I shall also discuss the use of kinesin motor proteins to power synthetic devices.

  11. FLA8/KIF3B phosphorylation regulates kinesin-II interaction with IFT-B to control IFT entry and turnaround.

    PubMed

    Liang, Yinwen; Pang, Yunong; Wu, Qiong; Hu, Zhangfeng; Han, Xue; Xu, Yisheng; Deng, Haiteng; Pan, Junmin

    2014-09-08

    The assembly and maintenance of cilia depends on intraflagellar transport (IFT). Activated IFT motor kinesin-II enters the cilium with loaded IFT particles comprising IFT-A and IFT-B complexes. At the ciliary tip, kinesin-II becomes inactivated, and IFT particles are released. Moreover, the rate of IFT entry is dynamically regulated during cilium assembly. However, the regulatory mechanism of IFT entry and loading/unloading of IFT particles remains elusive. We show that the kinesin-II motor subunit FLA8, a homolog of KIF3B, is phosphorylated on the conserved S663 by a calcium-dependent kinase in Chlamydomonas. This phosphorylation disrupts the interaction between kinesin-II and IFT-B, inactivates kinesin-II and inhibits IFT entry, and is also required for IFT-B unloading at the ciliary tip. Furthermore, our data suggest that the IFT entry rate is controlled by regulation of the cellular level of phosphorylated FLA8. Therefore, FLA8 phosphorylation acts as a molecular switch to control IFT entry and turnaround.

  12. The kinesin-2 family member KIF3C regulates microtubule dynamics and is required for axon growth and regeneration.

    PubMed

    Gumy, Laura F; Chew, Daniel J; Tortosa, Elena; Katrukha, Eugene A; Kapitein, Lukas C; Tolkovsky, Aviva M; Hoogenraad, Casper C; Fawcett, James W

    2013-07-10

    Axon regeneration after injury requires the extensive reconstruction, reorganization, and stabilization of the microtubule cytoskeleton in the growth cones. Here, we identify KIF3C as a key regulator of axonal growth and regeneration by controlling microtubule dynamics and organization in the growth cone. KIF3C is developmentally regulated. Rat embryonic sensory axons and growth cones contain undetectable levels of KIF3C protein that is locally translated immediately after injury. In adult neurons, KIF3C is axonally transported from the cell body and is enriched at the growth cone where it preferentially binds to tyrosinated microtubules. Functionally, the interaction of KIF3C with EB3 is necessary for its localization at the microtubule plus-ends in the growth cone. Depletion of KIF3C in adult neurons leads to an increase in stable, overgrown and looped microtubules because of a strong decrease in the microtubule frequency of catastrophes, suggesting that KIF3C functions as a microtubule-destabilizing factor. Adult axons lacking KIF3C, by RNA interference or KIF3C gene knock-out, display an impaired axonal outgrowth in vitro and a delayed regeneration after injury both in vitro and in vivo. Murine KIF3C knock-out embryonic axons grow normally but do not regenerate after injury because they are unable to locally translate KIF3C. These data show that KIF3C is an injury-specific kinesin that contributes to axon growth and regeneration by regulating and organizing the microtubule cytoskeleton in the growth cone.

  13. DNA based molecular motors

    NASA Astrophysics Data System (ADS)

    Michaelis, Jens; Muschielok, Adam; Andrecka, Joanna; Kügel, Wolfgang; Moffitt, Jeffrey R.

    2009-12-01

    Most of the essential cellular processes such as polymerisation reactions, gene expression and regulation are governed by mechanical processes. Controlled mechanical investigations of these processes are therefore required in order to take our understanding of molecular biology to the next level. Single-molecule manipulation and force spectroscopy have over the last 15 years been developed into extremely powerful techniques. Applying these techniques to the investigation of proteins and DNA molecules has led to a mechanistic understanding of protein function on the level of single molecules. As examples for DNA based molecular machines we will describe single-molecule experiments on RNA polymerases as well as on the packaging of DNA into a viral capsid-a process that is driven by one of the most powerful molecular motors.

  14. Molecular Motors and Stochastic Models

    NASA Astrophysics Data System (ADS)

    Lipowsky, Reinhard

    The behavior of single molecular motors such as kinesin or myosin V, which move on linear filaments, involves a nontrivial coupling between the biochemical motor cycle and the stochastic movement. This coupling can be studied in the framework of nonuniform ratchet models which are characterized by spatially localized transition rates between the different internal states of the motor. These models can be classified according to their functional relationships between the motor velocity and the concentration of the fuel molecules. The simplest such relationship applies to two subclasses of models for dimeric kinesin and agrees with experimental observations on this molecular motor.

  15. Combined Deletion of Vhl and Kif3a Accelerates Renal Cyst Formation

    PubMed Central

    Lehmann, Holger; Vicari, Daniele; Wild, Peter J.

    2015-01-01

    A subset of familial and sporadic clear cell renal cell carcinomas (ccRCCs) is believed to develop from cystic precursor lesions. Loss of function of the von Hippel-Lindau tumor suppressor gene (VHL) predisposes renal epithelial cells to loss of the primary cilium in response to specific signals. Because the primary cilium suppresses renal cyst formation, loss of the cilium may be an initiating event in the formation of ccRCC. To test this hypothesis, we analyzed the consequences of inducible renal epithelium–specific deletion of Vhl together with ablation of the primary cilium via deletion of the kinesin family member 3A (Kif3a) gene. We developed a microcomputed tomography–based imaging approach to allow quantitative longitudinal monitoring of cystic burden, revealing that combined loss of Vhl and Kif3a shortened the latency of cyst initiation, increased the number of cysts per kidney, and increased the total cystic burden. In contrast with findings in other cystic models, cysts in Kif3a mutant mice did not display accumulation of hypoxia-inducible factor 1-α (HIF1α), and deletion of both Hif1a and Kif3a did not affect cyst development or progression. Vhl/Kif3a double mutation also increased the frequency of cysts that displayed multilayered epithelial growth, which correlated with an increased frequency of misoriented cystic epithelial cell divisions. These results argue against the involvement of HIF1α in promoting renal cyst growth and suggest that the formation of simple and atypical renal cysts that resemble ccRCC precursor lesions is greatly accelerated by the combined loss of Vhl and the primary cilium. PMID:25788526

  16. Combined Deletion of Vhl and Kif3a Accelerates Renal Cyst Formation.

    PubMed

    Lehmann, Holger; Vicari, Daniele; Wild, Peter J; Frew, Ian J

    2015-11-01

    A subset of familial and sporadic clear cell renal cell carcinomas (ccRCCs) is believed to develop from cystic precursor lesions. Loss of function of the von Hippel-Lindau tumor suppressor gene (VHL) predisposes renal epithelial cells to loss of the primary cilium in response to specific signals. Because the primary cilium suppresses renal cyst formation, loss of the cilium may be an initiating event in the formation of ccRCC. To test this hypothesis, we analyzed the consequences of inducible renal epithelium-specific deletion of Vhl together with ablation of the primary cilium via deletion of the kinesin family member 3A (Kif3a) gene. We developed a microcomputed tomography-based imaging approach to allow quantitative longitudinal monitoring of cystic burden, revealing that combined loss of Vhl and Kif3a shortened the latency of cyst initiation, increased the number of cysts per kidney, and increased the total cystic burden. In contrast with findings in other cystic models, cysts in Kif3a mutant mice did not display accumulation of hypoxia-inducible factor 1-α (HIF1α), and deletion of both Hif1a and Kif3a did not affect cyst development or progression. Vhl/Kif3a double mutation also increased the frequency of cysts that displayed multilayered epithelial growth, which correlated with an increased frequency of misoriented cystic epithelial cell divisions. These results argue against the involvement of HIF1α in promoting renal cyst growth and suggest that the formation of simple and atypical renal cysts that resemble ccRCC precursor lesions is greatly accelerated by the combined loss of Vhl and the primary cilium.

  17. Combined deletion of Vhl, Trp53 and Kif3a causes cystic and neoplastic renal lesions.

    PubMed

    Guinot, Anna; Lehmann, Holger; Wild, Peter J; Frew, Ian J

    2016-07-01

    The von Hippel-Lindau (VHL) tumour suppressor gene is bi-allelically inactivated in the majority of cases of clear cell renal cell carcinoma (ccRCC); however, Vhl knockout mouse models do not recapitulate human ccRCC, implying that additional mutations are required for tumour formation. Mutational inactivation of VHL sensitises renal epithelial cells to lose the primary cilium in response to other mutations or extracellular stimuli. Loss of cilia is believed to represent a second hit in VHL mutant cells that causes the development of cystic lesions that, in some cases, can progress to ccRCC. Supporting this idea, genetic ablation of the primary cilium by deletion of the kinesin family member 3A (Kif3a) gene cooperates with loss of Vhl to accelerate cyst formation in mouse kidneys. Additionally, aged Vhl/Trp53 double-mutant mice develop renal cysts and tumours at a relatively low incidence, suggesting that there is a genetic cooperation between VHL and TP53 mutation in the development of ccRCC. Here we generated renal epithelium-specific Kif3a/Trp53 and Vhl/Kif3a/Trp53 mutant mice to investigate whether primary cilium deletion would accelerate the development of cystic precursor lesions or cause their progression to ccRCC. Longitudinal microcomputed tomography (μCT) imaging and histopathological analyses revealed an increased rate of cyst formation, increased proportion of cysts with proliferating cells, higher frequency of atypical cysts as well as the development of neoplasms in Vhl/Kif3a/Trp53 mutant kidneys compared to Kif3a/Trp53 or Vhl/Kif3a mutant kidneys. These findings demonstrate that primary cilium loss, in addition to Vhl and Trp53 losses, promotes the transition towards malignancy and provide further evidence that the primary cilium functions as a tumour suppressor organelle in the kidney. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. The mechanochemistry of molecular motors.

    PubMed Central

    Keller, D; Bustamante, C

    2000-01-01

    A theory of molecular motors is presented that explains how the energy released in single chemical reactions can generate mechanical motion and force. In the simplest case the fluctuating movements of a motor enzyme are well described by a diffusion process on a two-dimensional potential energy surface, where one dimension is a chemical reaction coordinate and the other is the spatial displacement of the motor. The coupling between chemistry and motion results from the shape of the surface, and motor velocities and forces result from diffusion currents on this surface. This microscopic description is shown to possess an equivalent kinetic mechanism in which the rate constants depend on externally applied forces. By using this equivalence we explore the characteristic properties of several broad classes of motor mechanisms and give general expressions for motor velocity versus load force for any member of each class. We show that in some cases simple plots of 1/velocity vs. 1/concentration can distinguish between classes of motor mechanisms and may be used to determine the step at which movement occurs. PMID:10653770

  19. Fluctuation Relations for Molecular Motors

    NASA Astrophysics Data System (ADS)

    Lacoste, David; Mallick, Kirone

    This review is focused on the application of specific fluctuation relations, such as the Gallavotti-Cohen relation, to ratchet models of a molecular motor. A special emphasis is placed on two-state models such as the flashing ratchet model. We derive the Gallavotti-Cohen fluctuation relation for these models and we discuss some of its implications.

  20. Nanotechnology Review: Molecular Electronics to Molecular Motors

    NASA Technical Reports Server (NTRS)

    Srivastava, Deepak; Saini, Subhash (Technical Monitor)

    1998-01-01

    Reviewing the status of current approaches and future projections, as already published in scientific journals and books, the talk will summarize the direction in which computational and experimental nanotechnologies are progressing. Examples of nanotechnological approaches to the concepts of design and simulation of carbon nanotube based molecular electronic and mechanical devices will be presented. The concepts of nanotube based gears and motors will be discussed. The above is a non-technical review talk which covers long term precompetitive basic research in already published material that has been presented before many US scientific meeting audiences.

  1. Duty ratio of cooperative molecular motors.

    PubMed

    Dharan, Nadiv; Farago, Oded

    2012-02-01

    Molecular motors are found throughout the cells of the human body and have many different and important roles. These micromachines move along filament tracks and have the ability to convert chemical energy into mechanical work that powers cellular motility. Different types of motors are characterized by different duty ratios, which is the fraction of time that a motor is attached to its filament. In the case of myosin II (a nonprocessive molecular machine with a low duty ratio), cooperativity between several motors is essential to induce motion along its actin filament track. In this work we use statistical mechanical tools to calculate the duty ratio of cooperative molecular motors. The model suggests that the effective duty ratio of nonprocessive motors that work in cooperation is lower than the duty ratio of the individual motors. The origin of this effect is the elastic tension that develops in the filament which is relieved when motors detach from the track.

  2. Duty ratio of cooperative molecular motors

    NASA Astrophysics Data System (ADS)

    Dharan, Nadiv; Farago, Oded

    2012-02-01

    Molecular motors are found throughout the cells of the human body and have many different and important roles. These micromachines move along filament tracks and have the ability to convert chemical energy into mechanical work that powers cellular motility. Different types of motors are characterized by different duty ratios, which is the fraction of time that a motor is attached to its filament. In the case of myosin II (a nonprocessive molecular machine with a low duty ratio), cooperativity between several motors is essential to induce motion along its actin filament track. In this work we use statistical mechanical tools to calculate the duty ratio of cooperative molecular motors. The model suggests that the effective duty ratio of nonprocessive motors that work in cooperation is lower than the duty ratio of the individual motors. The origin of this effect is the elastic tension that develops in the filament which is relieved when motors detach from the track.

  3. Molecular motors and their functions in plants

    NASA Technical Reports Server (NTRS)

    Reddy, A. S.

    2001-01-01

    Molecular motors that hydrolyze ATP and use the derived energy to generate force are involved in a variety of diverse cellular functions. Genetic, biochemical, and cellular localization data have implicated motors in a variety of functions such as vesicle and organelle transport, cytoskeleton dynamics, morphogenesis, polarized growth, cell movements, spindle formation, chromosome movement, nuclear fusion, and signal transduction. In non-plant systems three families of molecular motors (kinesins, dyneins, and myosins) have been well characterized. These motors use microtubules (in the case of kinesines and dyneins) or actin filaments (in the case of myosins) as tracks to transport cargo materials intracellularly. During the last decade tremendous progress has been made in understanding the structure and function of various motors in animals. These studies are yielding interesting insights into the functions of molecular motors and the origin of different families of motors. Furthermore, the paradigm that motors bind cargo and move along cytoskeletal tracks does not explain the functions of some of the motors. Relatively little is known about the molecular motors and their roles in plants. In recent years, by using biochemical, cell biological, molecular, and genetic approaches a few molecular motors have been isolated and characterized from plants. These studies indicate that some of the motors in plants have novel features and regulatory mechanisms. The role of molecular motors in plant cell division, cell expansion, cytoplasmic streaming, cell-to-cell communication, membrane trafficking, and morphogenesis is beginning to be understood. Analyses of the Arabidopsis genome sequence database (51% of genome) with conserved motor domains of kinesin and myosin families indicates the presence of a large number (about 40) of molecular motors and the functions of many of these motors remain to be discovered. It is likely that many more motors with novel regulatory

  4. Ratchet models of molecular motors

    NASA Astrophysics Data System (ADS)

    Jaster, Nicole

    2003-09-01

    Transport processes in and of cells are of major importance for the survival of the organism. Muscles have to be able to contract, chromosomes have to be moved to opposing ends of the cell during mitosis, and organelles, which are compartments enclosed by membranes, have to be transported along molecular tracks. Molecular motors are proteins whose main task is moving other molecules.For that purpose they transform the chemical energy released in the hydrolysis of ATP into mechanical work. The motors of the cytoskeleton belong to the three super families myosin, kinesin and dynein. Their tracks are filaments of the cytoskeleton, namely actin and the microtubuli. Here, we examine stochastic models which are used for describing the movements of these linear molecular motors. The scale of the movements comprises the regime of single steps of a motor protein up to the directed walk along a filament. A single step bridges around 10 nm, depending on the protein, and takes about 10 ms, if there is enough ATP available. Our models comprise M states or conformations the motor can attain during its movement along a one-dimensional track. At K locations along the track transitions between the states are possible. The velocity of the protein depending on the transition rates between the single states can be determined analytically. We calculate this velocity for systems of up to four states and locations and are able to derive a number of rules which are helpful in estimating the behaviour of an arbitrary given system. Beyond that we have a look at decoupled subsystems, i.e., one or a couple of states which have no connection to the remaining system. With a certain probability a motor undergoes a cycle of conformational changes, with another probability an independent other cycle. Active elements in real transport processes by molecular motors will not be limited to the transitions between the states. In distorted networks or starting from the discrete Master equation of the

  5. Molecular Motors: Power Strokes Outperform Brownian Ratchets.

    PubMed

    Wagoner, Jason A; Dill, Ken A

    2016-07-07

    Molecular motors convert chemical energy (typically from ATP hydrolysis) to directed motion and mechanical work. Their actions are often described in terms of "Power Stroke" (PS) and "Brownian Ratchet" (BR) mechanisms. Here, we use a transition-state model and stochastic thermodynamics to describe a range of mechanisms ranging from PS to BR. We incorporate this model into Hill's diagrammatic method to develop a comprehensive model of motor processivity that is simple but sufficiently general to capture the full range of behavior observed for molecular motors. We demonstrate that, under all conditions, PS motors are faster, more powerful, and more efficient at constant velocity than BR motors. We show that these differences are very large for simple motors but become inconsequential for complex motors with additional kinetic barrier steps.

  6. Molecular switches and motors on surfaces.

    PubMed

    Pathem, Bala Krishna; Claridge, Shelley A; Zheng, Yue Bing; Weiss, Paul S

    2013-01-01

    Molecular switches and motors respond structurally, electronically, optically, and/or mechanically to external stimuli, testing and potentially enabling extreme miniaturization of optoelectronic devices, nanoelectromechanical systems, and medical devices. The assembly of motors and switches on surfaces makes it possible both to measure the properties of individual molecules as they relate to their environment and to couple function between assembled molecules. In this review, we discuss recent progress in assembling molecular switches and motors on surfaces, measuring static and dynamic structures, understanding switching mechanisms, and constructing functional molecular materials and devices. As demonstrative examples, we choose a representative molecule from three commonly studied classes including molecular switches, photochromic molecules, and mechanically interlocked molecules. We conclude by offering perspectives on the future of molecular switches and motors on surfaces.

  7. Bio-inspired novel design principles for artificial molecular motors.

    PubMed

    Hugel, Thorsten; Lumme, Christina

    2010-10-01

    Since we have learned that biological organisms like ourselves are driven by tiny biological molecular motors we try to design and produce artificial molecular motors. However, despite the huge efforts since decades, man-made artificial molecular motors are still far from biological molecular motors or macroscopic motors with regard to performance, especially with respect to energy efficiency. This review highlights recent progress towards artificial molecular motors and discusses how their design and development can be guided by the design concepts of biological molecular motors or macroscopic motors.

  8. Molecular motors: thermodynamics and the random walk.

    PubMed Central

    Thomas, N.; Imafuku, Y.; Tawada, K.

    2001-01-01

    The biochemical cycle of a molecular motor provides the essential link between its thermodynamics and kinetics. The thermodynamics of the cycle determine the motor's ability to perform mechanical work, whilst the kinetics of the cycle govern its stochastic behaviour. We concentrate here on tightly coupled, processive molecular motors, such as kinesin and myosin V, which hydrolyse one molecule of ATP per forward step. Thermodynamics require that, when such a motor pulls against a constant load f, the ratio of the forward and backward products of the rate constants for its cycle is exp [-(DeltaG + u(0)f)/kT], where -DeltaG is the free energy available from ATP hydrolysis and u(0) is the motor's step size. A hypothetical one-state motor can therefore act as a chemically driven ratchet executing a biased random walk. Treating this random walk as a diffusion problem, we calculate the forward velocity v and the diffusion coefficient D and we find that its randomness parameter r is determined solely by thermodynamics. However, real molecular motors pass through several states at each attachment site. They satisfy a modified diffusion equation that follows directly from the rate equations for the biochemical cycle and their effective diffusion coefficient is reduced to D-v(2)tau, where tau is the time-constant for the motor to reach the steady state. Hence, the randomness of multistate motors is reduced compared with the one-state case and can be used for determining tau. Our analysis therefore demonstrates the intimate relationship between the biochemical cycle, the force-velocity relation and the random motion of molecular motors. PMID:11600075

  9. Development of an electrically driven molecular motor.

    PubMed

    Murphy, Colin J; Sykes, E Charles H

    2014-10-01

    For molecules to be used as components in molecular machinery, methods are required that couple individual molecules to external energy sources in order to selectively excite motion in a given direction. While significant progress has been made in the construction of synthetic molecular motors powered by light and by chemical reactions, there are few experimental examples of electrically driven molecular motors. To this end, we pioneered the use of a new, stable and tunable molecular rotor system based on surface-bound thioethers to comprehensively study many aspects of molecular rotation. As biological molecular motors often operate at interfaces, our synthetic system is especially amenable to microscopic interrogation as compared to solution-based systems. Using scanning tunneling microscopy (STM) and density functional theory, we studied the rotation of surface-bound thioethers, which can be induced either thermally or by electrons from the STM tip in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. This work culminated in the first experimental demonstration of a single-molecule electric motor, where the electrically driven rotation of a butyl methyl sulfide molecule adsorbed on a copper surface could be directionally biased. The direction and rate of the rotation are related to the chirality of both the molecule and the STM tip (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices.

  10. Unidirectional rotary motion in achiral molecular motors.

    PubMed

    Kistemaker, Jos C M; Štacko, Peter; Visser, Johan; Feringa, Ben L

    2015-11-01

    Control of the direction of motion is an essential feature of biological rotary motors and results from the intrinsic chirality of the amino acids from which the motors are made. In synthetic autonomous light-driven rotary motors, point chirality is transferred to helical chirality, and this governs their unidirectional rotation. However, achieving directional rotary motion in an achiral molecular system in an autonomous fashion remains a fundamental challenge. Here, we report an achiral molecular motor in which the presence of a pseudo-asymmetric carbon atom proved to be sufficient for exclusive autonomous disrotary motion of two appended rotor moieties. Isomerization around the two double bonds enables both rotors to move in the same direction with respect to their surroundings--like wheels on an axle--demonstrating that autonomous unidirectional rotary motion can be achieved in a symmetric system.

  11. Unidirectional rotary motion in achiral molecular motors

    NASA Astrophysics Data System (ADS)

    Kistemaker, Jos C. M.; Štacko, Peter; Visser, Johan; Feringa, Ben L.

    2015-11-01

    Control of the direction of motion is an essential feature of biological rotary motors and results from the intrinsic chirality of the amino acids from which the motors are made. In synthetic autonomous light-driven rotary motors, point chirality is transferred to helical chirality, and this governs their unidirectional rotation. However, achieving directional rotary motion in an achiral molecular system in an autonomous fashion remains a fundamental challenge. Here, we report an achiral molecular motor in which the presence of a pseudo-asymmetric carbon atom proved to be sufficient for exclusive autonomous disrotary motion of two appended rotor moieties. Isomerization around the two double bonds enables both rotors to move in the same direction with respect to their surroundings—like wheels on an axle—demonstrating that autonomous unidirectional rotary motion can be achieved in a symmetric system.

  12. Mechanochemical models of processive molecular motors

    NASA Astrophysics Data System (ADS)

    Lan, Ganhui; Sun, Sean X.

    2012-05-01

    Motor proteins are the molecular engines powering the living cell. These nanometre-sized molecules convert chemical energy, both enthalpic and entropic, into useful mechanical work. High resolution single molecule experiments can now observe motor protein movement with increasing precision. The emerging data must be combined with structural and kinetic measurements to develop a quantitative mechanism. This article describes a modelling framework where quantitative understanding of motor behaviour can be developed based on the protein structure. The framework is applied to myosin motors, with emphasis on how synchrony between motor domains give rise to processive unidirectional movement. The modelling approach shows that the elasticity of protein domains are important in regulating motor function. Simple models of protein domain elasticity are presented. The framework can be generalized to other motor systems, or an ensemble of motors such as muscle contraction. Indeed, for hundreds of myosins, our framework can be reduced to the Huxely-Simmons description of muscle movement in the mean-field limit.

  13. Universal optimal working cycles of molecular motors.

    PubMed

    Efremov, Artem; Wang, Zhisong

    2011-04-07

    Molecular motors capable of directional track-walking or rotation are abundant in living cells, and inspire the emerging field of artificial nanomotors. Some biomotors can convert 90% of free energy from chemical fuels into usable mechanical work, and the same motors still maintain a speed sufficient for cellular functions. This study exposed a new regime of universal optimization that amounts to a thermodynamically best working regime for molecular motors but is unfamiliar in macroscopic engines. For the ideal case of zero energy dissipation, the universally optimized working cycle for molecular motors is infinitely slow like Carnot cycle for heat engines. But when a small amount of energy dissipation reduces energy efficiency linearly from 100%, the speed is recovered exponentially due to Boltzmann's law. Experimental data on a major biomotor (kinesin) suggest that the regime of universal optimization has been largely approached in living cells, underpinning the extreme efficiency-speed trade-off in biomotors. The universal optimization and its practical approachability are unique thermodynamic advantages of molecular systems over macroscopic engines in facilitating motor functions. The findings have important implications for the natural evolution of biomotors as well as the development of artificial counterparts.

  14. Mechanoregulation of molecular motors in flagella

    NASA Astrophysics Data System (ADS)

    Gadelha, Hermes

    2014-11-01

    Molecular motors are nano-biological machines responsible for exerting forces that drive movement in living organisms, from cargo transport to cell division and motility. Interestingly, despite the inherent complexity of many interacting motors, order and structure may arise naturally, as exemplified by the harmonic, self-organized undulatory motion of the flagellum. The real mechanisms behind this collective spontaneous oscillation are still unknown, and it is challenging task to measure experimentally the molecular motor dynamics within the flagellar structure in real time. In this talk we will explore different competing hypotheses that are capable of generating flagellar bending waves that ``resemble'' in-vitro observations, emphasizing the need for further mathematical analysis and model validation. It also highlight that this is a fertile and challenging area of inter-disciplinary research for applied mathematicians and demonstrates the importance of future observational and theoretical studies in understanding the underlying mechanics of these motile cell appendages.

  15. Unidirectional molecular motor on a gold surface

    NASA Astrophysics Data System (ADS)

    van Delden, Richard A.; Ter Wiel, Matthijs K. J.; Pollard, Michael M.; Vicario, Javier; Koumura, Nagatoshi; Feringa, Ben L.

    2005-10-01

    Molecules capable of mimicking the function of a wide range of mechanical devices have been fabricated, with motors that can induce mechanical movement attracting particular attention. Such molecular motors convert light or chemical energy into directional rotary or linear motion, and are usually prepared and operated in solution. But if they are to be used as nanomachines that can do useful work, it seems essential to construct systems that can function on a surface, like a recently reported linear artificial muscle. Surface-mounted rotors have been realized and limited directionality in their motion predicted. Here we demonstrate that a light-driven molecular motor capable of repetitive unidirectional rotation can be mounted on the surface of gold nanoparticles. The motor design uses a chiral helical alkene with an upper half that serves as a propeller and is connected through a carbon-carbon double bond (the rotation axis) to a lower half that serves as a stator. The stator carries two thiol-functionalized `legs', which then bind the entire motor molecule to a gold surface. NMR spectroscopy reveals that two photo-induced cis-trans isomerizations of the central double bond, each followed by a thermal helix inversion to prevent reverse rotation, induce a full and unidirectional 360° rotation of the propeller with respect to the surface-mounted lower half of the system.

  16. Thermodynamics and kinetics of molecular motors.

    PubMed

    Astumian, R Dean

    2010-06-02

    Molecular motors are first and foremost molecules, governed by the laws of chemistry rather than of mechanics. The dynamical behavior of motors based on chemical principles can be described as a random walk on a network of states. A key insight is that any molecular motor in solution explores all possible motions and configurations at thermodynamic equilibrium. By using input energy and chemical design to prevent motion that is not wanted, what is left behind is the motion that is desired. This review is focused on two-headed motors such as kinesin and Myosin V that move on a polymeric track. By use of microscopic reversibility, it is shown that the ratio between the number of forward steps and the number of backward steps in any sufficiently long time period does not directly depend on the mechanical properties of the linker between the two heads. Instead, this ratio is governed by the relative chemical specificity of the heads in the front-versus-rear position for the fuel, adenosine triphosphate and its products, adenosine diphosphate and inorganic phosphate. These insights have been key factors in the design of biologically inspired synthetic molecular walkers constructed out of DNA or out of small organic molecules.

  17. Thermodynamics and Kinetics of Molecular Motors

    PubMed Central

    Astumian, R. Dean

    2010-01-01

    Abstract Molecular motors are first and foremost molecules, governed by the laws of chemistry rather than of mechanics. The dynamical behavior of motors based on chemical principles can be described as a random walk on a network of states. A key insight is that any molecular motor in solution explores all possible motions and configurations at thermodynamic equilibrium. By using input energy and chemical design to prevent motion that is not wanted, what is left behind is the motion that is desired. This review is focused on two-headed motors such as kinesin and Myosin V that move on a polymeric track. By use of microscopic reversibility, it is shown that the ratio between the number of forward steps and the number of backward steps in any sufficiently long time period does not directly depend on the mechanical properties of the linker between the two heads. Instead, this ratio is governed by the relative chemical specificity of the heads in the front-versus-rear position for the fuel, adenosine triphosphate and its products, adenosine diphosphate and inorganic phosphate. These insights have been key factors in the design of biologically inspired synthetic molecular walkers constructed out of DNA or out of small organic molecules. PMID:20513383

  18. Propagation Modeling and Analysis of Molecular Motors in Molecular Communication.

    PubMed

    Chahibi, Youssef; Akyildiz, Ian F; Balasingham, Ilangko

    2016-10-24

    Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

  19. Propagation Modeling and Analysis of Molecular Motors in Molecular Communication.

    PubMed

    Chahibi, Youssef; Akyildiz, Ian F; Balasingham, Ilangko

    2016-12-01

    Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

  20. High-Pressure Microscopy for Studying Molecular Motors.

    PubMed

    Nishiyama, Masayoshi

    2015-01-01

    Movement is a fundamental characteristic of all living things. This biogenic function is carried out by various nanometer-sized molecular machines. Molecular motor is a typical molecular machinery in which the characteristic features of proteins are integrated; these include enzymatic activity, energy conversion, molecular recognition and self-assembly. These biologically important reactions occur with the association of water molecules that surround the motors. Applied pressures can alter the intermolecular interactions between the motors and water. In this chapter we describe the development of a high-pressure microscope and a new motility assay that enables the visualization of the motility of molecular motors under conditions of high-pressure. Our results demonstrate that applied pressure dynamically changes the motility of molecular motors such as kinesin, F1-ATPase and bacterial flagellar motors.

  1. Light-Driven Chiral Molecular Motors for Passive Agile Filters

    DTIC Science & Technology

    2014-05-20

    AFRL-OSR-VA-TR-2014-0121 LIGHT-DRIVEN CHIRAL MOLECULAR MOTORS FOR PASSIVE AGILE FILTERS Quan Li KENT STATE UNIV OH Final Report 05/20/2014...Prescribed by ANSI Std. Z39.18 1 FINAL REPORT Title: Light-driven Chiral Molecular Motors for Passive Agile Filters AFOSR...As we proposed originally, the major objective of this project was to synthesize novel light- driven chiral molecular motors or switches targeted

  2. Theoretical Analysis of Dynamic Processes for Interacting Molecular Motors.

    PubMed

    Teimouri, Hamid; Kolomeisky, Anatoly B; Mehrabiani, Kareem

    2015-02-13

    Biological transport is supported by collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by analyzing a new class of totally asymmetric exclusion processes where interactions are accounted for in a thermodynamically consistent fashion. It allows us to connect explicitly microscopic features of motor proteins with their collective dynamic properties. Theoretical analysis that combines various mean-field calculations and computer simulations suggests that dynamic properties of molecular motors strongly depend on interactions, and correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motors transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed.

  3. Theoretical analysis of dynamic processes for interacting molecular motors

    NASA Astrophysics Data System (ADS)

    Teimouri, Hamid; Kolomeisky, Anatoly B.; Mehrabiani, Kareem

    2015-02-01

    Biological transport is supported by the collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by carrying out an analysis of a new class of totally asymmetric exclusion processes, in which interactions are accounted for in a thermodynamically consistent fashion. This allows us to explicitly connect microscopic features of motor proteins with their collective dynamic properties. A theoretical analysis that combines various mean-field calculations and computer simulations suggests that the dynamic properties of molecular motors strongly depend on the interactions, and that the correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motor transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed.

  4. Thermodynamics and kinetics of a molecular motor ensemble.

    PubMed Central

    Baker, J E; Thomas, D D

    2000-01-01

    If, contrary to conventional models of muscle, it is assumed that molecular forces equilibrate among rather than within molecular motors, an equation of state and an expression for energy output can be obtained for a near-equilibrium, coworking ensemble of molecular motors. These equations predict clear, testable relationships between motor structure, motor biochemistry, and ensemble motor function, and we discuss these relationships in the context of various experimental studies. In this model, net work by molecular motors is performed with the relaxation of a near-equilibrium intermediate step in a motor-catalyzed reaction. The free energy available for work is localized to this step, and the rate at which this free energy is transferred to work is accelerated by the free energy of a motor-catalyzed reaction. This thermodynamic model implicitly deals with a motile cell system as a dynamic network (not a rigid lattice) of molecular motors within which the mechanochemistry of one motor influences and is influenced by the mechanochemistry of other motors in the ensemble. PMID:11023881

  5. Thermodynamics and kinetics of a molecular motor ensemble.

    PubMed

    Baker, J E; Thomas, D D

    2000-10-01

    If, contrary to conventional models of muscle, it is assumed that molecular forces equilibrate among rather than within molecular motors, an equation of state and an expression for energy output can be obtained for a near-equilibrium, coworking ensemble of molecular motors. These equations predict clear, testable relationships between motor structure, motor biochemistry, and ensemble motor function, and we discuss these relationships in the context of various experimental studies. In this model, net work by molecular motors is performed with the relaxation of a near-equilibrium intermediate step in a motor-catalyzed reaction. The free energy available for work is localized to this step, and the rate at which this free energy is transferred to work is accelerated by the free energy of a motor-catalyzed reaction. This thermodynamic model implicitly deals with a motile cell system as a dynamic network (not a rigid lattice) of molecular motors within which the mechanochemistry of one motor influences and is influenced by the mechanochemistry of other motors in the ensemble.

  6. Cytoskeleton Molecular Motors: Structures and Their Functions in Neuron.

    PubMed

    Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip

    2016-01-01

    Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons.

  7. Length regulation of active biopolymers by molecular motors.

    PubMed

    Johann, Denis; Erlenkämper, Christoph; Kruse, Karsten

    2012-06-22

    For biopolymers like cytoskeletal actin filaments and microtubules, assembly and disassembly are inherently dissipative processes. Molecular motors can affect the rates of subunit removal at filament ends. We introduce a driven lattice-gas model to study the effects of motor-induced depolymerization on the length of active biopolymers and find that increasing motor activity sharpens unimodal steady-state length distributions. Furthermore, for sufficiently fast moving motors, the relative width of the length distribution is determined only by the attachment rate of motors. Our results show how established molecular processes can be used to robustly regulate the size of cytoskeletal structures like mitotic spindles.

  8. Cytoskeleton Molecular Motors: Structures and Their Functions in Neuron

    PubMed Central

    Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip

    2016-01-01

    Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons. PMID:27570482

  9. Distinct transport regimes for two elastically coupled molecular motors.

    PubMed

    Berger, Florian; Keller, Corina; Klumpp, Stefan; Lipowsky, Reinhard

    2012-05-18

    Cooperative cargo transport by two molecular motors involves an elastic motor-motor coupling, which can reduce the motors' velocity and/or enhance their unbinding from the filament. We show theoretically that these interference effects lead, in general, to four distinct transport regimes. In addition to a weak coupling regime, kinesin and dynein motors are found to exhibit a strong coupling and an enhanced unbinding regime, whereas myosin motors are predicted to attain a reduced velocity regime. All of these regimes, which we derive by explicit calculations and general time scale arguments, can be explored experimentally by varying the elastic coupling strength.

  10. A general two-cycle network model of molecular motors

    NASA Astrophysics Data System (ADS)

    Zhang, Yunxin

    2009-09-01

    Molecular motors are single macromolecules that generate forces at the piconewton range and nanometer scale. They convert chemical energy into mechanical work by moving along filamentous structures. In this paper, we study the velocity of two-head molecular motors in the framework of a mechanochemical network theory. The network model, a generalization of the recently work of Liepelt and Lipowsky [Steffen Liepelt, Reinhard Lipowsky, Kinesins network of chemomechanical motor cycles, Physical Review Letters 98 (25) (2007) 258102], is based on the discrete mechanochemical states of a molecular motor with multiple cycles. By generalizing the mathematical method developed by Fisher and Kolomeisky for a single cycle motor [Michael E. Fisher, Anatoly B. Kolomeisky, Simple mechanochemistry describes the dynamics of kinesin molecules, Proceedings of the National Academy of Sciences 98 (14) (2001) 7748-7753], we are able to obtain an explicit formula for the velocity of a molecular motor.

  11. Unidirectional light-driven molecular motors based on overcrowded alkenes.

    PubMed

    Cnossen, Arjen; Browne, Wesley R; Feringa, Ben L

    2014-01-01

    Over the last two decades, interest in nanotechnology has led to the design and synthesis of a toolbox of nanoscale versions of macroscopic devices and components. In molecular nanotechnology, linear motors based on rotaxanes and rotary motors based on overcrowded alkenes are particularly promising for performing work at the nanoscale. In this chapter, progress on light-driven molecular motors based on overcrowded alkenes is reviewed. Both the so-called first and second generation molecular motors are discussed, as well as their potential applications.

  12. Motor Proteins and Molecular Motors: How to Operate Machines at Nanoscale

    PubMed Central

    Kolomeisky, Anatoly B.

    2013-01-01

    Several classes of biological molecules that transform chemical energy into mechanical work are known as motor proteins or molecular motors. These nanometer-sized machines operate in noisy stochastic isothermal environment, strongly supporting fundamental cellular processes such as transfer of genetic information, transport, organization and functioning. In last two decades motor proteins have become a subject of intense research efforts that were aimed to uncover fundamental principles and mechanisms of molecular motors dynamics. In this review, we critically discuss a recent progress in experimental and theoretical studies on motor proteins. Our focus is on analyzing fundamental concepts and ideas that have been utilized for explaining non-equilibrium nature and mechanisms of molecular motors. PMID:24100357

  13. Motor proteins and molecular motors: how to operate machines at the nanoscale.

    PubMed

    Kolomeisky, Anatoly B

    2013-11-20

    Several classes of biological molecules that transform chemical energy into mechanical work are known as motor proteins or molecular motors. These nanometer-sized machines operate in noisy stochastic isothermal environments, strongly supporting fundamental cellular processes such as the transfer of genetic information, transport, organization and functioning. In the past two decades motor proteins have become a subject of intense research efforts, aimed at uncovering the fundamental principles and mechanisms of molecular motor dynamics. In this review, we critically discuss recent progress in experimental and theoretical studies on motor proteins. Our focus is on analyzing fundamental concepts and ideas that have been utilized to explain the non-equilibrium nature and mechanisms of molecular motors.

  14. Collective alignment of polar filaments by molecular motors.

    PubMed

    Ziebert, F; Vershinin, M; Gross, S P; Aranson, I S

    2009-04-01

    We study the alignment of polar biofilaments, such as microtubules and actin, subject to the action of multiple molecular motors attached simultaneously to more than one filament. Focusing on a paradigm model of only two filaments interacting with multiple motors, we were able to investigate in detail the alignment dynamics. While almost no alignment occurs in the case of a single motor, the filaments become rapidly aligned due to the collective action of the motors. Our analysis shows that the alignment time is governed by the number of bound motors and the magnitude of the motors' stepping fluctuations. We predict that the time scale of alignment is in the order of seconds, much faster than that reported for passive crosslink-induced bundling. In vitro experiments on the alignment of microtubules by multiple-motor covered beads are in qualitative agreement. We also discuss another mode of fast alignment of filaments, namely the cooperation between motors and passive crosslinks.

  15. Exploiting molecular motors as nanomachines: the mechanisms of de novo and re-engineered cytoskeletal motors.

    PubMed

    DelRosso, Nicole V; Derr, Nathan D

    2017-01-11

    Cytoskeletal molecular motors provide exciting proof that nanoscale transporters can be highly efficient, moving for microns along filamentous tracks by hydrolyzing ATP to fuel nanometer-size steps. For nanotechnology, such conversion of chemical energy into productive work serves as an enticing platform for re-purposing and re-engineering. It also provides a roadmap for successful molecular mechanisms that can be mimicked to create de novo molecular motors for nanotechnology applications. Here we focus specifically on how the mechanisms of molecular motors are being re-engineered for greater control over their transport parameters. We then discuss mechanistic work to create fully synthetic motors de novo and conclude with future directions in creating novel motor systems.

  16. Helicases as molecular motors: An insight

    NASA Astrophysics Data System (ADS)

    Tuteja, Narendra; Tuteja, Renu

    2006-12-01

    Helicases are one of the smallest motors of biological system, which harness the chemical free energy of ATP hydrolysis to catalyze the opening of energetically stable duplex nucleic acids and thereby are involved in almost all aspect of nucleic acid metabolism including replication, repair, recombination, transcription, translation, and ribosome biogenesis. Basically, they break the hydrogen bonding between the duplex helix and translocate unidirectionally along the bound strand. Mostly all the helicases contain some conserved signature motifs, which act as an engine to power the unwinding. After the discovery of the first prokaryotic DNA helicase from Escherichia coli bacteria in 1976 and the first eukaryotic one from the lily plant in 1978, many more (>100) have been isolated. All the helicases share some common properties, including nucleic acid binding, NTP hydrolysis and unwinding of the duplex. Many helicases have been crystallized and their structures have revealed an underlying common structural fold for their function. The defects in helicases gene have also been reported to be responsible for variety of human genetic disorders, which can lead to cancer, premature aging or mental retardation. Recently, a new role of a helicase in abiotic stress signaling in plant has been discovered. Overall, helicases act as essential molecular tools for cellular machinery and help in maintaining the integrity of genome. Here an overview of helicases has been covered which includes history, biochemical assay, properties, classification, role in human disease and mechanism of unwinding and translocation.

  17. Molecular motors as an auto-oscillator

    PubMed Central

    Ishiwata, Shin’ichi; Shimamoto, Yuta; Suzuki, Madoka

    2010-01-01

    The organization of biomotile systems possesses structural and functional hierarchy, building up from single molecules via protein assemblies and cells further up to an organ. A typical example is the hierarchy of cardiac muscle, on the top of which is the heart. The heartbeat is supported by the rhythmic contraction of the muscle cells that is controlled by the Ca2+ oscillation triggered by periodic electrical excitation of pacemaker cells. Thus, it is usually believed that the heartbeat is governed by the control system based on a sequential one-way chain with the electrical∕chemical information transfer from the upper to the lower level of hierarchy. On the other hand, it has been known for many years that the contractile system of muscle, i.e., skinned muscle fibers and myofibrils, itself possesses the auto-oscillatory properties even in the constant chemical environment. A recent paper [Plaçais, et al. (2009), Phys. Rev. Lett. 103, 158102] demonstrated the auto-oscillatory movement∕tension development in an in vitro motility assay composed of a single actin filament and randomly distributed myosin II molecules, suggesting that the auto-oscillatory properties are inherent to the contractile proteins. Here we discuss how the molecular motors may acquire the higher-ordered auto-oscillatory properties while stepping up the staircase of hierarchy. PMID:21119762

  18. Monte Carlo simulations of single and coupled synthetic molecular motors.

    PubMed

    Chen, C-M; Zuckermann, M

    2012-11-01

    We use a minimal model to study the processive motion of coupled synthetic molecular motors along a DNA track and we present data from Monte Carlo (MC) computer simulations based on this model. The model was originally proposed by Bromley et al. [HFSP J. 3, 204 (2009)] for studying the properties of a synthetic protein motor, the "Tumbleweed" (TW), and involves rigid Y-shaped motors diffusively rotating along the track while controlled by a series of periodically injected ligand pulses into the solution. The advantage of the model is that it mimics the mechanical properties of the TW motor in detail. Both the average first passage time which measures the diffusive motion of the motors, and the average dwell time on the track which measures their processivity are investigated by varying the parameters of the model. The latter includes ligand concentration and the range and strength of the binding interaction between motors and the track. In particular, it is of experimental interest to study the dependence of these dynamic time scales of the motors on the ligand concentration. Single rigid TW motors were first studied since no previous MC simulations of these motors have been performed. We first studied single motors for which we found a logarithmic decrease of the average first passage time and a logarithmic increase of the average dwell time with increasing ligand concentration. For two coupled motors, the dependence on ligand concentration is still logarithmic for the average first passage time but becomes linear for the average dwell time. This suggests a much greater stability in the processive motion of coupled motors as compared to single motors in the limit of large ligand concentration. By increasing the number of coupled motors, m, it was found that the average first passage time of the coupled motors only increases slowly with m while the average dwell time increases exponentially with m. Thus the stability of coupled motors on the track can be

  19. Fluctuation theorem for the flashing ratchet model of molecular motors

    NASA Astrophysics Data System (ADS)

    Lacoste, D.; Mallick, K.

    2009-08-01

    Molecular motors convert chemical energy derived from the hydrolysis of adenosine triphosphate (ATP) into mechanical energy. A well-studied model of a molecular motor is the flashing ratchet model. We show that this model exhibits a fluctuation relation known as the Gallavotti-Cohen symmetry. Our study highlights the fact that the symmetry is present only if the chemical and mechanical degrees of freedom are both included in the description.

  20. Fluctuation theorem for the flashing ratchet model of molecular motors.

    PubMed

    Lacoste, D; Mallick, K

    2009-08-01

    Molecular motors convert chemical energy derived from the hydrolysis of adenosine triphosphate (ATP) into mechanical energy. A well-studied model of a molecular motor is the flashing ratchet model. We show that this model exhibits a fluctuation relation known as the Gallavotti-Cohen symmetry. Our study highlights the fact that the symmetry is present only if the chemical and mechanical degrees of freedom are both included in the description.

  1. Molecular motor traffic: From biological nanomachines to macroscopic transport

    NASA Astrophysics Data System (ADS)

    Lipowsky, Reinhard; Chai, Yan; Klumpp, Stefan; Liepelt, Steffen; Müller, Melanie J. I.

    2006-12-01

    All cells of animals and plants contain complex transport systems based on molecular motors which walk along cytoskeletal filaments. These motors are rather small and have a size of 20-100 nm but are able to pull vesicles, organelles and other types of cargo over large distances, from micrometers up to meters. There are several families of motors: kinesins, dyneins, and myosins. Most of these motors have two heads which are used as legs and perform discrete steps along the filaments. Several aspects of the motor behavior will be discussed: motor cycles of two-headed motors; walks of single motors or cargo particles which consist of directed movements interrupted by random, diffusive motion; cargo transport through tube-like compartments; active diffusion of cargo particles in slab-like compartments; cooperative transport of cargo by several motors which may be uni- or bi-directional; and systems with many interacting motors that exhibit traffic jams, self-organized density and flux patterns, and traffic phase transitions far from equilibrium. It is necessary to understand these traffic phenomena in a quantitative manner in order to construct and optimize biomimetic transport systems based on motors and filaments with many possible applications in bioengineering, pharmacology, and medicine.

  2. Molecular motors: a traffic cop within?

    PubMed Central

    Welte, M. A.; Gross, S. P.

    2008-01-01

    Intracellular transport along microtubules is often bidirectional, employing multiple plus- and minus-end directed motors. How cells regulate such transport in time and space is a fundamental but unsolved question in cell biology. A recent paper presents a new modeling approach to predict how much of transport can be understood just from our knowledge of the motors involved. The model can generate strikingly complex patterns of motion, mimicking key aspects of cargo transport in vivo. Previous studies had inferred that plus-end motors on bidirectional cargoes are usually turned off when the minus-end motors are engaged (and vice versa). In the model, such motor coordination can arise from motors competing in a tug-of-war, without help from additional regulators. This new theoretical framework should stimulate much research that will help unravel whether regulation of intracellular transport is dominated by higher-order control mechanisms or is achieved simply by tuning basic properties of the motors themselves. PMID:19404428

  3. How molecular motors shape the flagellar beat

    PubMed Central

    Riedel-Kruse, Ingmar H.; Hilfinger, Andreas; Howard, Jonathon; Jülicher, Frank

    2007-01-01

    Cilia and eukaryotic flagella are slender cellular appendages whose regular beating propels cells and microorganisms through aqueous media. The beat is an oscillating pattern of propagating bends generated by dynein motor proteins. A key open question is how the activity of the motors is coordinated in space and time. To elucidate the nature of this coordination we inferred the mechanical properties of the motors by analyzing the shape of beating sperm: Steadily beating bull sperm were imaged and their shapes were measured with high precision using a Fourier averaging technique. Comparing our experimental data with wave forms calculated for different scenarios of motor coordination we found that only the scenario of interdoublet sliding regulating motor activity gives rise to satisfactory fits. We propose that the microscopic origin of such “sliding control” is the load dependent detachment rate of motors. Agreement between observed and calculated wave forms was obtained only if significant sliding between microtubules occurred at the base. This suggests a novel mechanism by which changes in basal compliance could reverse the direction of beat propagation. We conclude that the flagellar beat patterns are determined by an interplay of the basal properties of the axoneme and the mechanical feedback of dynein motors. PMID:19404446

  4. Towards synthetic molecular motors: a model elastic-network study

    NASA Astrophysics Data System (ADS)

    Sarkar, Amartya; Flechsig, Holger; Mikhailov, Alexander S.

    2016-04-01

    Protein molecular motors play a fundamental role in biological cells and development of their synthetic counterparts is a major challenge. Here, we show how a model motor system with the operation mechanism resembling that of muscle myosin can be designed at the concept level, without addressing the implementation aspects. The model is constructed as an elastic network, similar to the coarse-grained descriptions used for real proteins. We show by numerical simulations that the designed synthetic motor can operate as a deterministic or Brownian ratchet and that there is a continuous transition between such two regimes. The motor operation under external load, approaching the stall condition, is also analysed.

  5. Molecular crowding creates traffic jams of kinesin motors on microtubules.

    PubMed

    Leduc, Cécile; Padberg-Gehle, Kathrin; Varga, Vladimír; Helbing, Dirk; Diez, Stefan; Howard, Jonathon

    2012-04-17

    Despite the crowdedness of the interior of cells, microtubule-based motor proteins are able to deliver cargoes rapidly and reliably throughout the cytoplasm. We hypothesize that motor proteins may be adapted to operate in crowded environments by having molecular properties that prevent them from forming traffic jams. To test this hypothesis, we reconstituted high-density traffic of purified kinesin-8 motor protein, a highly processive motor with long end-residency time, along microtubules in a total internal-reflection fluorescence microscopy assay. We found that traffic jams, characterized by an abrupt increase in the density of motors with an associated abrupt decrease in motor speed, form even in the absence of other obstructing proteins. To determine the molecular properties that lead to jamming, we altered the concentration of motors, their processivity, and their rate of dissociation from microtubule ends. Traffic jams occurred when the motor density exceeded a critical value (density-induced jams) or when motor dissociation from the microtubule ends was so slow that it resulted in a pileup (bottleneck-induced jams). Through comparison of our experimental results with theoretical models and stochastic simulations, we characterized in detail under which conditions density- and bottleneck-induced traffic jams form or do not form. Our results indicate that transport kinesins, such as kinesin-1, may be evolutionarily adapted to avoid the formation of traffic jams by moving only with moderate processivity and dissociating rapidly from microtubule ends.

  6. Molecular crowding creates traffic jams of kinesin motors on microtubules

    PubMed Central

    Leduc, Cécile; Padberg-Gehle, Kathrin; Varga, Vladimír; Helbing, Dirk; Diez, Stefan; Howard, Jonathon

    2012-01-01

    Despite the crowdedness of the interior of cells, microtubule-based motor proteins are able to deliver cargoes rapidly and reliably throughout the cytoplasm. We hypothesize that motor proteins may be adapted to operate in crowded environments by having molecular properties that prevent them from forming traffic jams. To test this hypothesis, we reconstituted high-density traffic of purified kinesin-8 motor protein, a highly processive motor with long end-residency time, along microtubules in a total internal-reflection fluorescence microscopy assay. We found that traffic jams, characterized by an abrupt increase in the density of motors with an associated abrupt decrease in motor speed, form even in the absence of other obstructing proteins. To determine the molecular properties that lead to jamming, we altered the concentration of motors, their processivity, and their rate of dissociation from microtubule ends. Traffic jams occurred when the motor density exceeded a critical value (density-induced jams) or when motor dissociation from the microtubule ends was so slow that it resulted in a pileup (bottleneck-induced jams). Through comparison of our experimental results with theoretical models and stochastic simulations, we characterized in detail under which conditions density- and bottleneck-induced traffic jams form or do not form. Our results indicate that transport kinesins, such as kinesin-1, may be evolutionarily adapted to avoid the formation of traffic jams by moving only with moderate processivity and dissociating rapidly from microtubule ends. PMID:22431622

  7. Cooperative behavior of molecular motors: Cargo transport and traffic phenomena

    NASA Astrophysics Data System (ADS)

    Lipowsky, Reinhard; Beeg, Janina; Dimova, Rumiana; Klumpp, Stefan; Müller, Melanie J. I.

    2010-01-01

    All eukaryotic cells including those of our own body contain complex transport systems based on molecular motors which walk along cytoskeletal filaments. These motors are rather small and make discrete mechanical steps with a step size of the order of 10 nm but are able to pull cargo particles over much larger distances, from micrometers up to meters. In vivo, the intracellular cargos include large membrane-bounded organelles, smaller vesicles, a subset of mRNAs, cytoskeletal filaments, and various protein building blocks, which are transported between different cell compartments. This cargo transport is usually performed by teams of motors. If all motors belong to the same molecular species, the cooperative action of the motors leads to uni-directional transport with a strongly increased run length and with a characteristic force dependence of the velocity distributions. If two antagonistic teams of motors pull on the same cargo particle, they perform a stochastic tug-of-war, which is characterized by a subtle force balance between the two motor teams and leads to several distinct patterns of bi-directional transport. So far, all experimental observations on bi-directional transport are consistent with such a tug-of-war. If many motors and/or cargo particles are transported along the filaments, one encounters various traffic phenomena. Depending on their mutual interactions and the compartment geometry, the motors form various spatio-temporal patterns such as traffic jams, and undergo nonequilibrium phase transitions between different patterns of transport.

  8. Tetrapodal molecular switches and motors: synthesis and photochemistry.

    PubMed

    Chen, Kuang-Yen; Wezenberg, Sander J; Carroll, Gregory T; London, Gábor; Kistemaker, Jos C M; Pijper, Thomas C; Feringa, Ben L

    2014-08-01

    The design, synthesis, and dynamic behavior of a series of novel tetrapodal molecular switches and motors containing common functional groups for attachment to various inorganic and organic surfaces are presented. Using a Diels-Alder reaction, an anthracene unit with four functionalized alkyl substituents ("legs") was coupled to maleimide-functionalized molecular switches or motors under ambient conditions. Terminal functional groups at the "legs" include thioacetates and azides, making these switches and motors ideal candidates for attachment to metallic or alkyne-functionalized surfaces. UV/vis absorption spectroscopy shows that the molecular switches and motors retain their ability to undergo reversible photoinduced and/or thermally induced structural changes after attachment to the tetrapodal anthracene.

  9. Engineering controllable bidirectional molecular motors based on myosin.

    PubMed

    Chen, Lu; Nakamura, Muneaki; Schindler, Tony D; Parker, David; Bryant, Zev

    2012-02-19

    Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

  10. Stochastic simulations of cargo transport by processive molecular motors

    NASA Astrophysics Data System (ADS)

    Korn, Christian B.; Klumpp, Stefan; Lipowsky, Reinhard; Schwarz, Ulrich S.

    2009-12-01

    We use stochastic computer simulations to study the transport of a spherical cargo particle along a microtubule-like track on a planar substrate by several kinesin-like processive motors. Our newly developed adhesive motor dynamics algorithm combines the numerical integration of a Langevin equation for the motion of a sphere with kinetic rules for the molecular motors. The Langevin part includes diffusive motion, the action of the pulling motors, and hydrodynamic interactions between sphere and wall. The kinetic rules for the motors include binding to and unbinding from the filament as well as active motor steps. We find that the simulated mean transport length increases exponentially with the number of bound motors, in good agreement with earlier results. The number of motors in binding range to the motor track fluctuates in time with a Poissonian distribution, both for springs and cables being used as models for the linker mechanics. Cooperativity in the sense of equal load sharing only occurs for high values for viscosity and attachment time.

  11. Embedding dual function into molecular motors through collective motion.

    PubMed

    Saito, Nen; Kaneko, Kunihiko

    2017-03-10

    Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently.

  12. Stochastic simulations of cargo transport by processive molecular motors.

    PubMed

    Korn, Christian B; Klumpp, Stefan; Lipowsky, Reinhard; Schwarz, Ulrich S

    2009-12-28

    We use stochastic computer simulations to study the transport of a spherical cargo particle along a microtubule-like track on a planar substrate by several kinesin-like processive motors. Our newly developed adhesive motor dynamics algorithm combines the numerical integration of a Langevin equation for the motion of a sphere with kinetic rules for the molecular motors. The Langevin part includes diffusive motion, the action of the pulling motors, and hydrodynamic interactions between sphere and wall. The kinetic rules for the motors include binding to and unbinding from the filament as well as active motor steps. We find that the simulated mean transport length increases exponentially with the number of bound motors, in good agreement with earlier results. The number of motors in binding range to the motor track fluctuates in time with a Poissonian distribution, both for springs and cables being used as models for the linker mechanics. Cooperativity in the sense of equal load sharing only occurs for high values for viscosity and attachment time.

  13. Embedding dual function into molecular motors through collective motion

    PubMed Central

    Saito, Nen; Kaneko, Kunihiko

    2017-01-01

    Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently. PMID:28281683

  14. Single rotating molecule-machines: nanovehicles and molecular motors.

    PubMed

    Rapenne, Gwénaël; Joachim, Christian

    2014-01-01

    In the last decade many molecular machines with controlled molecular motions have been synthesized. In the present review chapter we will present and discuss our contribution to the field, in particular through some examples of rotating molecular machines that have been designed, synthesized, and studied in our group. After starting by explaining why it is so important to study such machines as single molecules, we will focus on two families of molecular machines, nanovehicles and molecular motors. The first members of the nanovehicle family are molecules with two triptycenes as wheels: the axle and the wheelbarrow. Then come the four-wheel nanocars. Since triptycene wheels are not very mobile on metallic surfaces, alternative wheels with a bowl-shape structure have also been synthesized and studied on surfaces. The molecular motors are built around ruthenium organometallic centers and have a piano-stool geometry with peripheric ferrocenyl groups.

  15. Controlled clockwise and anticlockwise rotational switching of a molecular motor.

    PubMed

    Perera, U G E; Ample, F; Kersell, H; Zhang, Y; Vives, G; Echeverria, J; Grisolia, M; Rapenne, G; Joachim, C; Hla, S-W

    2013-01-01

    The design of artificial molecular machines often takes inspiration from macroscopic machines. However, the parallels between the two systems are often only superficial, because most molecular machines are governed by quantum processes. Previously, rotary molecular motors powered by light and chemical energy have been developed. In electrically driven motors, tunnelling electrons from the tip of a scanning tunnelling microscope have been used to drive the rotation of a simple rotor in a single direction and to move a four-wheeled molecule across a surface. Here, we show that a stand-alone molecular motor adsorbed on a gold surface can be made to rotate in a clockwise or anticlockwise direction by selective inelastic electron tunnelling through different subunits of the motor. Our motor is composed of a tripodal stator for vertical positioning, a five-arm rotor for controlled rotations, and a ruthenium atomic ball bearing connecting the static and rotational parts. The directional rotation arises from sawtooth-like rotational potentials, which are solely determined by the internal molecular structure and are independent of the surface adsorption site.

  16. Molecular motors and the 2nd law of thermodynamics

    NASA Astrophysics Data System (ADS)

    Wang, Zhisong

    2014-03-01

    Molecular motors from biology and nanotechnology often operate on chemical energy of fuel molecules in an isothermal environment, unlike macroscopic heat engines that draw energy from a heat flow between two temperatures. Nevertheless, isothermal molecular motors are still subject to the 2nd law of thermodynamics in a fundamental way: their directional motion must cost a finite amount of energy other than the environmental heat even though no work is done; otherwise the 2nd law would be violated. Hence the 2nd law requires a finite energy price for pure direction of molecular motors. But what is the lowest price of direction allowed by the 2nd law? And how does the 2nd law-decreed price of direction limit performance of molecular motors? In the talk, I shall present our theoretical study of the 2nd law-molecular motor link on basis of the accumulated biomotor phenomenology, and also introduce our experimental effort to develop biomimetic DNA bipedal nanomotors following the mechanistic guidelines out of the theoretical study. [Main contents of this talk are from references:] This work is partially supported by FRC grants R-144-000-259-112, R-144-000-290-112 and R-144-000-320-112.

  17. Controlled clockwise and anticlockwise rotational switching of a molecular motor

    NASA Astrophysics Data System (ADS)

    Perera, U. G. E.; Ample, F.; Kersell, H.; Zhang, Y.; Vives, G.; Echeverria, J.; Grisolia, M.; Rapenne, G.; Joachim, C.; Hla, S.-W.

    2013-01-01

    The design of artificial molecular machines often takes inspiration from macroscopic machines. However, the parallels between the two systems are often only superficial, because most molecular machines are governed by quantum processes. Previously, rotary molecular motors powered by light and chemical energy have been developed. In electrically driven motors, tunnelling electrons from the tip of a scanning tunnelling microscope have been used to drive the rotation of a simple rotor in a single direction and to move a four-wheeled molecule across a surface. Here, we show that a stand-alone molecular motor adsorbed on a gold surface can be made to rotate in a clockwise or anticlockwise direction by selective inelastic electron tunnelling through different subunits of the motor. Our motor is composed of a tripodal stator for vertical positioning, a five-arm rotor for controlled rotations, and a ruthenium atomic ball bearing connecting the static and rotational parts. The directional rotation arises from sawtooth-like rotational potentials, which are solely determined by the internal molecular structure and are independent of the surface adsorption site.

  18. Controlled Rotation and Manipulation of Individual Molecular Motors

    NASA Astrophysics Data System (ADS)

    Kersell, Heath; Perera, U. G. E.; Ample, F.; Zhang, Y.; Vives, G.; Echeverria, J.; Grisolia, M.; Rapenne, G.; Joachim, C.; Hla, S.-W.

    2015-03-01

    The design of artificial molecular machines often takes inspiration from macroscopic machines, but the parallels between the two are frequently only superficial because many molecular machines are governed by quantum processes. Previously, chemically and light driven rotary molecular motors have been developed. For electrically driven motors, tunneling electrons from the tip of a scanning tunneling microscope (STM) have been used to drive rotation in a simple rotor into a single direction and to move a wheeled molecule across a surface. Here, we show that a single standalone molecular motor adsorbed on a gold surface can be made to rotate in a clockwise or counterclockwise direction [1] by selective inelastic electron tunneling through different sub-units of the motor. Our motor is composed of a tripodal stator for vertical positioning, a five-arm rotator for controlled rotations, and a Ru atomic ball bearing connecting the static and rotational parts. The directional rotation originates from saw-tooth-like rotational potentials, which are determined by the internal molecular structure and are independent of the surface adsorption site. This project is supported by the US DOE, BES grant: DE-FG02-02ER46012.

  19. Mechanism of Spontaneous Oscillation Emerging from Collective Molecular Motors

    NASA Astrophysics Data System (ADS)

    Shimamoto, Yuta; Ishiwata, Shin'ichi

    2008-04-01

    Biological systems include a large number and various kinds of molecular machines. Individual molecular machines work stochastically, while the systems constructed of the ensembles of these machines exhibit dynamically-ordered phenomena, rather than a simple sum of individual parts. Here we focus on the spontaneous oscillatory contraction (SPOC) observed in the contractile system of muscle. From the mechanical measurements in the precursor state of SPOC, we discuss how the functions of individual molecular motors are autonomously regulated in the contractile system.

  20. Coiled coils and SAH domains in cytoskeletal molecular motors.

    PubMed

    Peckham, Michelle

    2011-10-01

    Cytoskeletal motors include myosins, kinesins and dyneins. Myosins move along tracks of actin filaments, whereas kinesins and dyneins move along microtubules. Many of these motors are involved in trafficking cargo in cells. However, myosins are mostly monomeric, whereas kinesins are mostly dimeric, owing to the presence of a coiled coil. Some myosins (myosins 6, 7 and 10) contain an SAH (single α-helical) domain, which was originally thought to be a coiled coil. These myosins are now known to be monomers, not dimers. The differences between SAH domains and coiled coils are described and the potential roles of SAH domains in molecular motors are discussed.

  1. Monte Carlo simulations of single and coupled synthetic molecular motors

    NASA Astrophysics Data System (ADS)

    Chen, C.-M.; Zuckermann, M.

    2012-11-01

    We use a minimal model to study the processive motion of coupled synthetic molecular motors along a DNA track and we present data from Monte Carlo (MC) computer simulations based on this model. The model was originally proposed by Bromley [HFSP J.10.2976/1.3111282 3, 204 (2009)] for studying the properties of a synthetic protein motor, the “Tumbleweed” (TW), and involves rigid Y-shaped motors diffusively rotating along the track while controlled by a series of periodically injected ligand pulses into the solution. The advantage of the model is that it mimics the mechanical properties of the TW motor in detail. Both the average first passage time which measures the diffusive motion of the motors, and the average dwell time on the track which measures their processivity are investigated by varying the parameters of the model. The latter includes ligand concentration and the range and strength of the binding interaction between motors and the track. In particular, it is of experimental interest to study the dependence of these dynamic time scales of the motors on the ligand concentration. Single rigid TW motors were first studied since no previous MC simulations of these motors have been performed. We first studied single motors for which we found a logarithmic decrease of the average first passage time and a logarithmic increase of the average dwell time with increasing ligand concentration. For two coupled motors, the dependence on ligand concentration is still logarithmic for the average first passage time but becomes linear for the average dwell time. This suggests a much greater stability in the processive motion of coupled motors as compared to single motors in the limit of large ligand concentration. By increasing the number of coupled motors, m, it was found that the average first passage time of the coupled motors only increases slowly with m while the average dwell time increases exponentially with m. Thus the stability of coupled motors on the track can

  2. Collective transport of weakly interacting molecular motors with Langmuir kinetics

    NASA Astrophysics Data System (ADS)

    Chandel, Sameep; Chaudhuri, Abhishek; Muhuri, Sudipto

    2015-04-01

    Filament-based intracellular transport involves the collective action of molecular motor proteins. Experimental evidences suggest that microtubule (MT) filament bound motor proteins such as kinesins weakly interact among themselves during transport and with the surrounding cellular environment. Motivated by these observations we study a driven lattice gas model for collective unidirectional transport of molecular motors on open filament. This model incorporates short-range next-nearest-neighbour (NNN) interactions between the motors and couples the transport process on filament with surrounding cellular environment through adsorption-desorption Langmuir kinetics (LK) of the motors. We analyse this model within the framework of a mean-field (MF) theory in the limit of weak interactions between the motors. We point to the mapping of this model with the non-conserved version of the Katz-Lebowitz-Spohn (KLS) model. The system exhibits rich phase behavior with a variety of inhomogeneous phases including localized shocks in the bulk of the filament. We obtain the steady-state density and current profiles, analyse their variation as a function of the strength of interaction and construct the non-equilibrium MF phase diagram. We compare these MF results with Monte Carlo simulations and find that the MF analysis shows reasonably good agreement with simulation results as long as the motors are weakly interacting. For sufficently strong NNN interaction between the motors, the mean-field results deviate significantly, and for very strong NNN interaction in the absence of LK, the current in the lattice is determined solely by the NNN interaction parameter and it becomes independent of entry and exit rates of motors at the filament boundaries.

  3. Patterns of molecular motors that guide and sort filaments.

    PubMed

    Rupp, Beat; Nédélec, François

    2012-11-21

    Molecular motors can be immobilized to transport filaments and loads that are attached to these filaments inside a nano-device. However, if motors are distributed uniformly over a flat surface, the motility is undirected, and the filaments move equally in all directions. For many applications it is important to control the direction in which the filaments move, and two strategies have been explored to achieve this: applying external forces and confining the filaments inside channels. In this article, we discuss a third strategy in which the topography of the sample remains flat, but the motors are distributed non-uniformly over the surface. Systems of filaments and patterned molecular motors were simulated using a stochastic engine that included Brownian motion and filament bending elasticity. Using an evolutionary algorithm, patterns were optimized for their capacity to precisely control the paths of the filaments. We identified patterns of motors that could either direct the filaments in a particular direction, or separate short and long filaments. These functionalities already exceed what has been achieved with confinement. The patterns are composed of one or two types of motors positioned in lines or along arcs and should be easy to manufacture. Finally, these patterns can be easily combined into larger designs, allowing one to precisely control the motion of microscopic objects inside a device.

  4. "Cargo-mooring" as an operating principle for molecular motors.

    PubMed

    Lisowski, Bartosz; Kuśmierz, Łukasz; Żabicki, Michał; Bier, Martin

    2015-06-07

    Navigating through an ever-changing and unsteady environment, and utilizing chemical energy, molecular motors transport the cell׳s crucial components, such as organelles and vesicles filled with neurotransmitter. They generate force and pull cargo, as they literally walk along the polymeric tracks, e.g. microtubules. What we suggest in this paper is that the motor protein is not really pulling its load. The load is subject to diffusion and the motor may be doing little else than rectifying the fluctuations, i.e. ratcheting the load׳s diffusion. Below we present a detailed model to show how such ratcheting can quantitatively account for observed data. The consequence of such a mechanism is the dependence of the transport׳s speed and efficacy not only on the motor, but also on the cargo (especially its size) and on the environment (i.e. its viscosity and structure). Current experimental works rarely provide this type of information for in vivo studies. We suggest that even small differences between assays can impact the outcome. Our results agree with those obtained in wet laboratories and provide novel insight in a molecular motor׳s functioning.

  5. Guiding Molecular Motors with Nano-Imprinted Structures

    NASA Astrophysics Data System (ADS)

    Bunk, Richard; Carlberg, Patrick; Månsson, Alf; Nicholls, Ian A.; Omling, Pär; Sundberg, Mark; Tågerud, Sven; Montelius, Lars

    2005-05-01

    This work, for the first time, demonstrates that nano-imprinted samples, with 100 nm wide polymer lines, can act as guides for molecular motors consisting of motor proteins actin and myosin. The motor protein function was characterized using fluorescence microscopy and compared to actomyosin motility on non-structured nitrocellulose surfaces. Our results open for further use of the nano-imprint technique in the production of disposable chips for bio-nanotechnological applications and miniaturized biological test systems. We discuss how the nano-imprinted motor protein assay system may be optimized and also how it compares to previously tested assay systems involving low-resolution UV-lithography and low throughput but high-resolution electron beam lithography.

  6. Time-dependent motor properties of multipedal molecular spiders

    NASA Astrophysics Data System (ADS)

    Samii, Laleh; Blab, Gerhard A.; Bromley, Elizabeth H. C.; Linke, Heiner; Curmi, Paul M. G.; Zuckermann, Martin J.; Forde, Nancy R.

    2011-09-01

    Molecular spiders are synthetic biomolecular walkers that use the asymmetry resulting from cleavage of their tracks to bias the direction of their stepping motion. Using Monte Carlo simulations that implement the Gillespie algorithm, we investigate the dependence of the biased motion of molecular spiders, along with binding time and processivity, on tunable experimental parameters, such as number of legs, span between the legs, and unbinding rate of a leg from a substrate site. We find that an increase in the number of legs increases the spiders’ processivity and binding time but not their mean velocity. However, we can increase the mean velocity of spiders with simultaneous tuning of the span and the unbinding rate of a spider leg from a substrate site. To study the efficiency of molecular spiders, we introduce a time-dependent expression for the thermodynamic efficiency of a molecular motor, allowing us to account for the behavior of spider populations as a function of time. Based on this definition, we find that spiders exhibit transient motor function over time scales of many hours and have a maximum efficiency on the order of 1%, weak compared to other types of molecular motors.

  7. Rotation of artificial rotor axles in rotary molecular motors.

    PubMed

    Baba, Mihori; Iwamoto, Kousuke; Iino, Ryota; Ueno, Hiroshi; Hara, Mayu; Nakanishi, Atsuko; Kishikawa, Jun-Ichi; Noji, Hiroyuki; Yokoyama, Ken

    2016-10-04

    F1- and V1-ATPase are rotary molecular motors that convert chemical energy released upon ATP hydrolysis into torque to rotate a central rotor axle against the surrounding catalytic stator cylinder with high efficiency. How conformational change occurring in the stator is coupled to the rotary motion of the axle is the key unknown in the mechanism of rotary motors. Here, we generated chimeric motor proteins by inserting an exogenous rod protein, FliJ, into the stator ring of F1 or of V1 and tested the rotation properties of these chimeric motors. Both motors showed unidirectional and continuous rotation, despite no obvious homology in amino acid sequence between FliJ and the intrinsic rotor subunit of F1 or V1 These results showed that any residue-specific interactions between the stator and rotor are not a prerequisite for unidirectional rotation of both F1 and V1 The torque of chimeric motors estimated from viscous friction of the rotation probe against medium revealed that whereas the F1-FliJ chimera generates only 10% of WT F1, the V1-FliJ chimera generates torque comparable to that of V1 with the native axle protein that is structurally more similar to FliJ than the native rotor of F1 This suggests that the gross structural mismatch hinders smooth rotation of FliJ accompanied with the stator ring of F1.

  8. Rotation of artificial rotor axles in rotary molecular motors

    PubMed Central

    Baba, Mihori; Iwamoto, Kousuke; Ueno, Hiroshi; Hara, Mayu; Nakanishi, Atsuko; Kishikawa, Jun-ichi; Noji, Hiroyuki; Yokoyama, Ken

    2016-01-01

    F1- and V1-ATPase are rotary molecular motors that convert chemical energy released upon ATP hydrolysis into torque to rotate a central rotor axle against the surrounding catalytic stator cylinder with high efficiency. How conformational change occurring in the stator is coupled to the rotary motion of the axle is the key unknown in the mechanism of rotary motors. Here, we generated chimeric motor proteins by inserting an exogenous rod protein, FliJ, into the stator ring of F1 or of V1 and tested the rotation properties of these chimeric motors. Both motors showed unidirectional and continuous rotation, despite no obvious homology in amino acid sequence between FliJ and the intrinsic rotor subunit of F1 or V1. These results showed that any residue-specific interactions between the stator and rotor are not a prerequisite for unidirectional rotation of both F1 and V1. The torque of chimeric motors estimated from viscous friction of the rotation probe against medium revealed that whereas the F1-FliJ chimera generates only 10% of WT F1, the V1-FliJ chimera generates torque comparable to that of V1 with the native axle protein that is structurally more similar to FliJ than the native rotor of F1. This suggests that the gross structural mismatch hinders smooth rotation of FliJ accompanied with the stator ring of F1. PMID:27647891

  9. Myosin-I molecular motors at a glance.

    PubMed

    McIntosh, Betsy B; Ostap, E Michael

    2016-07-15

    Myosin-I molecular motors are proposed to play various cellular roles related to membrane dynamics and trafficking. In this Cell Science at a Glance article and the accompanying poster, we review and illustrate the proposed cellular functions of metazoan myosin-I molecular motors by examining the structural, biochemical, mechanical and cell biological evidence for their proposed molecular roles. We highlight evidence for the roles of myosin-I isoforms in regulating membrane tension and actin architecture, powering plasma membrane and organelle deformation, participating in membrane trafficking, and functioning as a tension-sensitive dock or tether. Collectively, myosin-I motors have been implicated in increasingly complex cellular phenomena, yet how a single isoform accomplishes multiple types of molecular functions is still an active area of investigation. To fully understand the underlying physiology, it is now essential to piece together different approaches of biological investigation. This article will appeal to investigators who study immunology, metabolic diseases, endosomal trafficking, cell motility, cancer and kidney disease, and to those who are interested in how cellular membranes are coupled to the underlying actin cytoskeleton in a variety of different applications.

  10. Biased motion and molecular motor properties of bipedal spiders.

    PubMed

    Samii, Laleh; Linke, Heiner; Zuckermann, Martin J; Forde, Nancy R

    2010-02-01

    Molecular spiders are synthetic molecular motors featuring multiple legs that each can interact with a substrate through binding and cleavage. Experimental studies suggest the motion of the spider in a matrix is biased toward uncleaved substrates and that spider properties such as processivity can be altered by changing the binding strength of the legs to substrate [R. Pei, S. K. Taylor, D. Stefanovic, S. Rudchenko, T. E. Mitchell, and M. N. Stojanovic, J. Am. Chem. Soc. 128, 12693 (2006)]. We investigate the origin of biased motion and molecular motor properties of bipedal spiders using Monte Carlo simulations. Our simulations combine a realistic chemical kinetic model, hand-over-hand or inchworm modes of stepping, and the use of a one-dimensional track. We find that stronger binding to substrate, cleavage and spider detachment from the track are contributing mechanisms to population bias. We investigate the contributions of stepping mechanism to speed, randomness parameter, processivity, coupling, and efficiency, and comment on how these molecular motor properties can be altered by changing experimentally tunable kinetic parameters.

  11. Biased motion and molecular motor properties of bipedal spiders

    NASA Astrophysics Data System (ADS)

    Samii, Laleh; Linke, Heiner; Zuckermann, Martin J.; Forde, Nancy R.

    2010-02-01

    Molecular spiders are synthetic molecular motors featuring multiple legs that each can interact with a substrate through binding and cleavage. Experimental studies suggest the motion of the spider in a matrix is biased toward uncleaved substrates and that spider properties such as processivity can be altered by changing the binding strength of the legs to substrate [R. Pei, S. K. Taylor, D. Stefanovic, S. Rudchenko, T. E. Mitchell, and M. N. Stojanovic, J. Am. Chem. Soc. 128, 12693 (2006)]. We investigate the origin of biased motion and molecular motor properties of bipedal spiders using Monte Carlo simulations. Our simulations combine a realistic chemical kinetic model, hand-over-hand or inchworm modes of stepping, and the use of a one-dimensional track. We find that stronger binding to substrate, cleavage and spider detachment from the track are contributing mechanisms to population bias. We investigate the contributions of stepping mechanism to speed, randomness parameter, processivity, coupling, and efficiency, and comment on how these molecular motor properties can be altered by changing experimentally tunable kinetic parameters.

  12. Universal bound on the efficiency of molecular motors

    NASA Astrophysics Data System (ADS)

    Pietzonka, Patrick; Barato, Andre C.; Seifert, Udo

    2016-12-01

    The thermodynamic uncertainty relation provides an inequality relating any mean current, the associated dispersion and the entropy production rate for arbitrary non-equilibrium steady states. Applying it here to a general model of a molecular motor running against an external force or torque, we show that the thermodynamic efficiency of such motors is universally bounded by an expression involving only experimentally accessible quantities. For motors pulling cargo through a viscous fluid, a universal bound for the corresponding Stokes efficiency follows as a variant. A similar result holds if mechanical force is used to synthesize molecules of high chemical potential. Crucially, no knowledge of the detailed underlying mechano-chemical mechanism is required for applying these bounds.

  13. Interferometric Scattering Microscopy for the Study of Molecular Motors.

    PubMed

    Andrecka, J; Takagi, Y; Mickolajczyk, K J; Lippert, L G; Sellers, J R; Hancock, W O; Goldman, Y E; Kukura, P

    2016-01-01

    Our understanding of molecular motor function has been greatly improved by the development of imaging modalities, which enable real-time observation of their motion at the single-molecule level. Here, we describe the use of a new method, interferometric scattering microscopy, for the investigation of motor protein dynamics by attaching and tracking the motion of metallic nanoparticle labels as small as 20nm diameter. Using myosin-5, kinesin-1, and dynein as examples, we describe the basic assays, labeling strategies, and principles of data analysis. Our approach is relevant not only for motor protein dynamics but also provides a general tool for single-particle tracking with high spatiotemporal precision, which overcomes the limitations of single-molecule fluorescence methods.

  14. Interferometric Scattering Microscopy for the Study of Molecular Motors

    PubMed Central

    Andrecka, J.; Takagi, Y.; Mickolajczyk, K.J.; Lippert, L.G.; Sellers, J.R.; Hancock, W.O.; Goldman, Y.E.; Kukura, P.

    2016-01-01

    Our understanding of molecular motor function has been greatly improved by the development of imaging modalities, which enable real-time observation of their motion at the single-molecule level. Here, we describe the use of a new method, interferometric scattering microscopy, for the investigation of motor protein dynamics by attaching and tracking the motion of metallic nanoparticle labels as small as 20 nm diameter. Using myosin-5, kinesin-1, and dynein as examples, we describe the basic assays, labeling strategies, and principles of data analysis. Our approach is relevant not only for motor protein dynamics but also provides a general tool for single-particle tracking with high spatiotemporal precision, which overcomes the limitations of single-molecule fluorescence methods. PMID:27793291

  15. ATOMIC AND MOLECULAR PHYSICS: Modelling of a DNA packaging motor

    NASA Astrophysics Data System (ADS)

    Qian, Jun; Xie, Ping; Xue, Xiao-Guang; Wang, Peng-Ye

    2009-11-01

    During the assembly of many viruses, a powerful molecular motor packages the genome into a preassembled capsid. The Bacillus subtilis phage phi29 is an excellent model system to investigate the DNA packaging mechanism because of its highly efficient in vitro DNA packaging activity and the development of a single-molecule packaging assay. Here we make use of structural and biochemical experimental data to build a physical model of DNA packaging by the phi29 DNA packaging motor. Based on the model, various dynamic behaviours such as the packaging rate, pause frequency and slip frequency under different ATP concentrations, ADP concentrations, external loads as well as capsid fillings are studied by using Monte Carlo simulation. Good agreement is obtained between the simulated and available experimental results. Moreover, we make testable predictions that should guide future experiments related to motor function.

  16. Chemically optimizing operational efficiency of molecular rotary motors.

    PubMed

    Conyard, Jamie; Cnossen, Arjen; Browne, Wesley R; Feringa, Ben L; Meech, Stephen R

    2014-07-09

    Unidirectional molecular rotary motors that harness photoinduced cis-trans (E-Z) isomerization are promising tools for the conversion of light energy to mechanical motion in nanoscale molecular machines. Considerable progress has been made in optimizing the frequency of ground-state rotation, but less attention has been focused on excited-state processes. Here the excited-state dynamics of a molecular motor with electron donor and acceptor substituents located to modify the excited-state reaction coordinate, without altering its stereochemistry, are studied. The substituents are shown to modify the photochemical yield of the isomerization without altering the motor frequency. By combining 50 fs resolution time-resolved fluorescence with ultrafast transient absorption spectroscopy the underlying excited-state dynamics are characterized. The Franck-Condon excited state relaxes in a few hundred femtoseconds to populate a lower energy dark state by a pathway that utilizes a volume conserving structural change. This is assigned to pyramidalization at a carbon atom of the isomerizing bridging double bond. The structure and energy of the dark state thus reached are a function of the substituent, with electron-withdrawing groups yielding a lower energy longer lived dark state. The dark state is coupled to the Franck-Condon state and decays on a picosecond time scale via a coordinate that is sensitive to solvent friction, such as rotation about the bridging bond. Neither subpicosecond nor picosecond dynamics are sensitive to solvent polarity, suggesting that intramolecular charge transfer and solvation are not key driving forces for the rate of the reaction. Instead steric factors and medium friction determine the reaction pathway, with the sterically remote substitution primarily influencing the energetics. Thus, these data indicate a chemical method of optimizing the efficiency of operation of these molecular motors without modifying their overall rotational frequency.

  17. Symposium FF: Molecular Motors, Nanomachines, and Active Nanostructures

    DTIC Science & Technology

    2008-06-23

    effects . Contributed talks by Francisco Raymo and Dongwhan Lee were followed by the second invited talk by Miguel Garcia-Garibay from UCLA...to 100 scientists in the audience for almost all talks. The large fraction of invited talks resulted in a consistently high quality of presentations...and engineers, and the large number of parallel symposia draws in attendees who are more peripherally interested in molecular motors. The main

  18. Mechanical transduction mechanisms of RecA-like molecular motors.

    PubMed

    Liao, Jung-Chi

    2011-12-01

    A majority of ATP-dependent molecular motors are RecA-like proteins, performing diverse functions in biology. These RecA-like molecular motors consist of a highly conserved core containing the ATP-binding site. Here I examined how ATP binding within this core is coupled to the conformational changes of different RecA-like molecular motors. Conserved hydrogen bond networks and conformational changes revealed two major mechanical transduction mechanisms: (1) intra-domain conformational changes and (2) inter-domain conformational changes. The intra-domain mechanism has a significant hydrogen bond rearrangement within the domain containing the P-loop, causing relative motion between two parts of the protein. The inter-domain mechanism exhibits little conformational change in the P-loop domain. Instead, the major conformational change is observed between the P-loop domain and an adjacent domain or subunit containing the arginine finger. These differences in the mechanical transduction mechanisms may link to the underlying energy surface governing a Brownian ratchet or a power stroke.

  19. Rotary molecular motion at the nanoscale: motors, propellers, wheels

    NASA Astrophysics Data System (ADS)

    Vukovic, Lela; Wang, Boyang; Kral, Petr

    2009-03-01

    We describe by molecular dynamics simulations nanoscale systems that could realize rotary motion. First, we study molecular propellers formed by carbon nanotube rotors with attached aromatic blades [1]. We show that these propellers could pump different types of liquids, and their pumping efficiency strongly depends on the chemistry of the (hydrophobic or hydrophilic) liquid-blade interface. We also investigate nanoscopic wheels with hydrophobic surfaces that show rolling activity on water when driven. Finally, we model efficient molecular motors driven by electron tunneling, which could drive rotary molecular systems [2]. [3pt] [1] B. Wang and P. Kr'al, . Rev. Lett. 98, 266102 (2007).[0pt] [2] B. Wang, L. Vukovic and P. Kr'al, Phys. Rev. Lett. 101, 186808 (2008).

  20. Ultrafast Excited State Dynamics in Molecular Motors: Coupling of Motor Length to Medium Viscosity.

    PubMed

    Conyard, Jamie; Stacko, Peter; Chen, Jiawen; McDonagh, Sophie; Hall, Christopher R; Laptenok, Sergey P; Browne, Wesley R; Feringa, Ben L; Meech, Stephen R

    2017-03-07

    Photochemically driven molecular motors convert the energy of incident radiation to intramolecular rotational motion. The motor molecules considered here execute four step unidirectional rotational motion. This comprises a pair of successive light induced isomerizations to a metastable state followed by thermal helix inversions. The internal rotation of a large molecular unit required in these steps is expected to be sensitive to both the viscosity of the medium and the volume of the rotating unit. In this work, we describe a study of motor motion in both ground and excited states as a function of the size of the rotating units. The excited state decay is ultrafast, highly non-single exponential, and is best described by a sum of three exponential relaxation components. The average excited state decay time observed for a series of motors with substituents of increasing volume was determined. While substitution does affect the lifetime, the size of the substituent has only a minor effect. The solvent polarity dependence is also slight, but there is a significant solvent viscosity effect. Increasing the viscosity has no effect on the fastest of the three decay components, but it does lengthen the two slower decay times, consistent with them being associated with motion along an intramolecular coordinate displacing a large solvent volume. However, these slower relaxation times are again not a function of the size of the substituent. We conclude that excited state decay arises from motion along a coordinate which does not necessarily require complete rotation of the substituents through the solvent, but is instead more localized in the core structure of the motor. The decay of the metastable state to the ground state through a helix inversion occurs 14 orders of magnitude more slowly than the excited state decay, and was measured as a function of substituent size, solvent viscosity and temperature. In this case neither substituent size nor solvent viscosity influences

  1. Operating principles of rotary molecular motors: differences between F1 and V1 motors.

    PubMed

    Yamato, Ichiro; Kakinuma, Yoshimi; Murata, Takeshi

    2016-01-01

    Among the many types of bioenergy-transducing machineries, F- and V-ATPases are unique bio- and nano-molecular rotary motors. The rotational catalysis of F1-ATPase has been investigated in detail, and molecular mechanisms have been proposed based on the crystal structures of the complex and on extensive single-molecule rotational observations. Recently, we obtained crystal structures of bacterial V1-ATPase (A3B3 and A3B3DF complexes) in the presence and absence of nucleotides. Based on these new structures, we present a novel model for the rotational catalysis mechanism of V1-ATPase, which is different from that of F1-ATPases.

  2. Microtubules and associated molecular motors in Neurospora crassa.

    PubMed

    Mouriño-Pérez, Rosa Reyna; Riquelme, Meritxell; Callejas-Negrete, Olga Alicia; Galván-Mendoza, José Iván

    2016-01-01

    The cytoskeleton provides structure, shape and movement to various cells. Microtubules (MTs) are tubular structures made of α and β-tubulin heterodimers organized in 13 protofilaments, forming a hollow cylinder. A vast group of MT-associated proteins determines the function, behavior and interaction of the MTs with other cellular components. Among these proteins, molecular motors such as the dynein-dynactin complex and kinesin superfamily play roles in MT organization and organelle transport. This article focuses on the MT cytoskeleton and associated molecular motors in the filamentous fungus Neurospora crassa In addition to reviewing current available information for this fungus and contrasting it with knowledge of other fungal species, we present new experimental results that support the role of dynein, dynactin and conventional kinesin in MT organization, dynamics and transport of subcellular structures (nuclei and secretory vesicles). In wild type hyphae of N. crassa, cytoplasmic MTs are arranged longitudinally along hyphae and display a helical curvature. They interlace with one another to form a network throughout the cytoplasm. N. crassa dynein and dynactin mutants have a scant and disorganized MT cytoskeleton, an erratic and reduced Spitzenkörper (Spk) and distorted hyphal morphology. In contrast, hyphae of mutants with defective conventional kinesin exhibit only minor disruptions in MT and Spk organization. Although nuclear positioning is affected in all mutants, the MT-associated motor proteins are not major contributors to nuclear movement during hyphal growth. Cytoplasmic bulk flow is the vehicle for nuclear displacement in growing hyphal regions of N. crassa Motors are involved in nuclei saltatory movements in both retrograde or anterograde direction. In the dynein and kinesin mutants, micro and macrovesicles can reach the Spk, although growth is slightly impaired and the Spk displays an erratic path. Hyphal growth requires MTs, and their associated

  3. Chemical and thermal modulation of molecular motor activities

    NASA Astrophysics Data System (ADS)

    Hong, Weili

    Molecular motors of kinesin and dynein families are responsible for various intracellular activities, from long distance movement of organelles, vesicles, protein complexes, and mRNAs to powering mitotic processes. They can take nanometer steps using chemical energy from the hydrolysis of ATP (adenosine triphosphate), and their dysfunction is involved in many neurodegenerative diseases that require long distance transport of cargos. Here I report on the study of the properties of molecular motors at a single-molecule level using optical trappings. I first studied the inhibition properties of kinesin motors by marine natural compound adociasulfates. I showed that adociasulfates compete with microtubules for binding to kinesins and thus inhibit kinesins' activity. Although adociasulfates are a strong inhibitor for all kinesin members, they show a much higher inhibition effect for conventional kinesins than for mitotic kinesins. Thus adociasulfates can be used to specifically inhibit conventional kinesins. By comparing the inhibition of kinesins by two structurally similar adociasulfates, one can see that the negatively charged sulfate residue of adociasulfates can be replaced by other negative residues and thus make it possible for adociasulfate-derived compounds to be more cell permeable. Kinesins and dyneins move cargos towards opposite directions along a microtubule. Cargos with both kinesins and dyneins attached often move bidirectionally due to undergoing a tug-of-war between the oppositely moving kinesin and dynein motors. Here I studied the effect of temperature on microtubule-based kinesin and dynein motor transport. While kinesins' and dyneins' velocities are closely matched above 15 °C, below this temperature the dyneins' velocity decreases much faster than the kinesins'. The kinesins' and dyneins' forces do not measurably change with temperature. The results suggest that temperature has significant effects on bidirectional transport and can be used to

  4. Facile assembly of light-driven molecular motors onto a solid surface.

    PubMed

    Chen, Jiawen; Chen, Kuang-Yen; Carroll, Gregory T; Feringa, Ben L

    2014-10-28

    In order to improve the rotary motion of surface assembled light-driven molecular motors, tetra-acid-functionalized motors were bound to an amine-coated quartz surface without prior activation of the acid groups. In contrast to earlier bipodal motors, the tetravalent motor showed no significant reduction in the rotation speed when attached to a surface.

  5. Traffic jams and shocks of molecular motors inside cellular protrusions.

    PubMed

    Pinkoviezky, I; Gov, N S

    2014-05-01

    Molecular motors are involved in key transport processes inside actin-based cellular protrusions. The motors carry cargo proteins to the protrusion tip which participate in regulating the actin polymerization and play a key role in facilitating the growth and formation of such protrusions. It is observed that the motors accumulate at the tips of cellular protrusions and form aggregates that are found to drift towards the protrusion base at the rate of actin treadmilling. We present a one-dimensional driven lattice model, where motors become inactive after delivering their cargo at the tip, or by loosing their cargo to a cargoless neighbor. The results suggest that the experimental observations may be explained by the formation of traffic jams that form at the tip. The model is solved using a novel application of mean-field and shock analysis. We find a new class of shocks that undergo intermittent collapses. Extensions with attachment and detachment events and relevance to experiments are briefly described.

  6. Optical Traps to Study Properties of Molecular Motors

    PubMed Central

    Spudich, James A.; Rice, Sarah E.; Rock, Ronald S.; Purcell, Thomas J.; Warrick, Hans M.

    2016-01-01

    In vitro motility assays enabled the analysis of coupling between ATP hydrolysis and movement of myosin along actin filaments or kinesin along microtubules. Single-molecule assays using laser trapping have been used to obtain more detailed information about kinesins, myosins, and processive DNA enzymes. The combination of in vitro motility assays with laser-trap measurements has revealed detailed dynamic structural changes associated with the ATPase cycle. This article describes the use of optical traps to study processive and nonprocessive molecular motor proteins, focusing on the design of the instrument and the assays to characterize motility. PMID:22046048

  7. Relation between cooperative molecular motors and active Brownian particles

    NASA Astrophysics Data System (ADS)

    Touya, Clément; Schwalger, Tilo; Lindner, Benjamin

    2011-05-01

    Active Brownian particles (ABPs), obeying a nonlinear Langevin equation with speed-dependent drift and noise amplitude, are well-known models used to describe self-propelled motion in biology. In this paper we study a model describing the stochastic dynamics of a group of coupled molecular motors (CMMs). Using two independent numerical methods, one based on the stationary velocity distribution of the motors and the other one on the local increments (also known as the Kramers-Moyal coefficients) of the velocity, we establish a connection between the CMM and the ABP models. The parameters extracted for the ABP via the two methods show good agreement for both symmetric and asymmetric cases and are independent of N, the number of motors, provided that N is not too small. This indicates that one can indeed describe the CMM problem with a simpler ABP model. However, the power spectrum of velocity fluctuations in the CMM model reveals a peak at a finite frequency, a peak which is absent in the velocity spectrum of the ABP model. This implies richer dynamic features of the CMM model which cannot be captured by an ABP model.

  8. Actin-based motility propelled by molecular motors

    NASA Astrophysics Data System (ADS)

    Upadyayula, Sai Pramod; Rangarajan, Murali

    2012-09-01

    Actin-based motility of Listeria monocytogenes propelled by filament end-tracking molecular motors has been simulated. Such systems may act as potential nanoscale actuators and shuttles useful in sorting and sensing biomolecules. Filaments are modeled as three-dimensional elastic springs distributed on one end of the capsule and persistently attached to the motile bacterial surface through an end-tracking motor complex. Filament distribution is random, and monomer concentration decreases linearly as a function of position on the bacterial surface. Filament growth rate increases with monomer concentration but decreases with the extent of compression. The growing filaments exert push-pull forces on the bacterial surface. In addition to forces, torques arise due to two factors—distribution of motors on the bacterial surface, and coupling of torsion upon growth due to the right-handed helicity of F-actin—causing the motile object to undergo simultaneous translation and rotation. The trajectory of the bacterium is simulated by performing a force and torque balance on the bacterium. All simulations use a fixed value of torsion. Simulations show strong alignment of the filaments and the long axis of the bacterium along the direction of motion. In the absence of torsion, the bacterial surface essentially moves along the direction of the long axis. When a small amount of the torsion is applied to the bacterial surface, the bacterium is seen to move in right-handed helical trajectories, consistent with experimental observations.

  9. Visible-Light Excitation of a Molecular Motor with an Extended Aromatic Core

    PubMed Central

    2017-01-01

    Exploring routes to visible-light-driven rotary motors, the possibility of red-shifting the excitation wavelength of molecular motors by extension of the aromatic core is studied. Introducing a dibenzofluorenyl moiety in a standard molecular motor resulted in red-shifting of the absorption spectrum. UV/vis and 1H NMR spectroscopy showed that these motors could be isomerized with light of wavelengths up to 490 nm and that the structural modification did not impair the anticipated rotary behavior. Extension of the aromatic core is therefore a suitable strategy to apply in pursuit of visible-light-driven molecular motors. PMID:28248510

  10. Stochastic thermodynamics of single enzymes and molecular motors.

    PubMed

    Seifert, U

    2011-03-01

    For a single enzyme or molecular motor operating in an aqueous solution of non-equilibrated solute concentrations, a thermodynamic description is developed on the level of an individual trajectory of transitions between states. The concept of internal energy, intrinsic entropy and free energy for states follows from a microscopic description using one assumption on time scale separation. A first-law energy balance then allows the unique identification of the heat dissipated in one transition. Consistency with the second law on the ensemble level enforces both stochastic entropy as third contribution to the entropy change involved in one transition and the local detailed balance condition for the ratio between forward and backward rates for any transition. These results follow without assuming weak coupling between the enzyme and the solutes, ideal solution behavior or mass action law kinetics. The present approach highlights both the crucial role of the intrinsic entropy of each state and the physically questionable role of chemiostats for deriving the first law for molecular motors subject to an external force under realistic conditions.

  11. Active fluidization of polymer networks through molecular motors.

    PubMed

    Humphrey, D; Duggan, C; Saha, D; Smith, D; Käs, J

    2002-03-28

    Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations.

  12. Stepping molecular motor amid Lévy white noise

    NASA Astrophysics Data System (ADS)

    Lisowski, Bartosz; Valenti, Davide; Spagnolo, Bernardo; Bier, Martin; Gudowska-Nowak, Ewa

    2015-04-01

    We consider a model of a stepping molecular motor consisting of two connected heads. Directional motion of the stepper takes place along a one-dimensional track. Each head is subject to a periodic potential without spatial reflection symmetry. When the potential for one head is switched on, it is switched off for the other head. Additionally, the system is subject to the influence of symmetric, white Lévy noise that mimics the action of external random forcing. The stepper exhibits motion with a preferred direction which is examined by analyzing the median of the displacement of a midpoint between the positions of the two heads. We study the modified dynamics of the stepper by numerical simulations. We find flux reversals as noise parameters are changed. Speed and direction appear to very sensitively depend on characteristics of the noise.

  13. External forces influence the elastic coupling effects during cargo transport by molecular motors.

    PubMed

    Berger, Florian; Keller, Corina; Klumpp, Stefan; Lipowsky, Reinhard

    2015-02-01

    Cellular transport is achieved by the cooperative action of molecular motors which are elastically linked to a common cargo. When the motors pull on the cargo at the same time, they experience fluctuating elastic strain forces induced by the stepping of the other motors. These elastic coupling forces can influence the motors' stepping and unbinding behavior and thereby the ability to transport cargos. Based on a generic single motor description, we introduce a framework that explains the response of two identical molecular motors to a constant external force. In particular, we relate the single motor parameters, the coupling strength and the external load force to the dynamics of the motor pair. We derive four distinct transport regimes and determine how the crossover lines between the regimes depend on the load force. Our description of the overall cargo dynamics takes into account relaxational displacements of the cargo caused by the unbinding of one motor. For large forces and weak elastic coupling these back-shifts dominate the displacements. To develop an intuitive understanding about motor cooperativity during cargo transport, we introduce a time scale for load sharing. This time scale allows us to predict how the regulation of single motor parameters influences the cooperativity. As an example, we show that up-regulating the single motor processivity enhances load sharing of the motor pair.

  14. Simulation studies of self-organization of microtubules and molecular motors.

    SciTech Connect

    Jian, Z.; Karpeev, D.; Aranson, I. S.; Bates, P. W.; Michigan State Univ.

    2008-05-01

    We perform Monte Carlo type simulation studies of self-organization of microtubules interacting with molecular motors. We model microtubules as stiff polar rods of equal length exhibiting anisotropic diffusion in the plane. The molecular motors are implicitly introduced by specifying certain probabilistic collision rules resulting in realignment of the rods. This approximation of the complicated microtubule-motor interaction by a simple instant collision allows us to bypass the 'computational bottlenecks' associated with the details of the diffusion and the dynamics of motors and the reorientation of microtubules. Consequently, we are able to perform simulations of large ensembles of microtubules and motors on a very large time scale. This simple model reproduces all important phenomenology observed in in vitro experiments: Formation of vortices for low motor density and raylike asters and bundles for higher motor density.

  15. Simulation studies of self-organization of microtubules and molecular motors

    NASA Astrophysics Data System (ADS)

    Jia, Zhiyuan; Karpeev, Dmitry; Aranson, Igor S.; Bates, Peter W.

    2008-05-01

    We perform Monte Carlo type simulation studies of self-organization of microtubules interacting with molecular motors. We model microtubules as stiff polar rods of equal length exhibiting anisotropic diffusion in the plane. The molecular motors are implicitly introduced by specifying certain probabilistic collision rules resulting in realignment of the rods. This approximation of the complicated microtubule-motor interaction by a simple instant collision allows us to bypass the “computational bottlenecks” associated with the details of the diffusion and the dynamics of motors and the reorientation of microtubules. Consequently, we are able to perform simulations of large ensembles of microtubules and motors on a very large time scale. This simple model reproduces all important phenomenology observed in in vitro experiments: Formation of vortices for low motor density and raylike asters and bundles for higher motor density.

  16. The reciprocal coordination and mechanics of molecular motors in living cells.

    PubMed

    Laib, Jeneva A; Marin, John A; Bloodgood, Robert A; Guilford, William H

    2009-03-03

    Molecular motors in living cells are involved in whole-cell locomotion, contractility, developmental shape changes, and organelle movement and positioning. Whether motors of different directionality are functionally coordinated in cells or operate in a semirandom "tug of war" is unclear. We show here that anterograde and retrograde microtubule-based motors in the flagella of Chlamydomonas are regulated such that only motors of a common directionality are engaged at any single time. A laser trap was used to position microspheres on the plasma membrane of immobilized paralyzed Chlamydomonas flagella. The anterograde and retrograde movements of the microsphere were measured with nanometer resolution as microtubule-based motors engaged the transmembrane protein FMG-1. An average of 10 motors acted to move the microsphere in either direction. Reversal of direction during a transport event was uncommon, and quiescent periods separated every transport event, suggesting the coordinated and exclusive action of only a single motor type. After a jump to 32 degrees C, temperature-sensitive mutants of kinesin-2 (fla10) showed exclusively retrograde transport events, driven by 7 motors on average. These data suggest that molecular motors in living cells can be reciprocally coordinated to engage simultaneously in large numbers and for exclusive transport in a single direction, even when a mixed population of motors is present. This offers a unique model for studying the mechanics, regulation, and directional coordination of molecular motors in a living intracellular environment.

  17. Enantiopure Functional Molecular Motors Obtained by a Switchable Chiral-Resolution Process.

    PubMed

    van Leeuwen, Thomas; Gan, Jefri; Kistemaker, Jos C M; Pizzolato, Stefano F; Chang, Mu-Chieh; Feringa, Ben L

    2016-05-17

    Molecular switches, rotors, and motors play an important role in the development of nano-machines and devices, as well as responsive and adaptive functional materials. For unidirectional rotors based on chiral overcrowded alkenes, their stereochemical homogeneity is of crucial importance. Herein, a method to obtain new and functionalizable overcrowded alkenes in enantiopure form is presented. The procedure involves a short synthesis of three steps and a solvent-switchable chiral resolution by using a readily available resolving agent. X-ray crystallography revealed the mode of binding of the motor with the resolving agent, as well as the absolute configuration of the motor. (1) H NMR and UV/Vis spectroscopy techniques were used to determine the dynamic behavior of this molecular motor. This method provides rapid access to ample amounts of enantiopure molecular motors, which will greatly facilitate the further development of responsive molecular systems based on chiral overcrowded alkenes.

  18. Harnessing molecular motors for nanoscale pulldown in live cells.

    PubMed

    Bird, Jonathan E; Barzik, Melanie; Drummond, Meghan C; Sutton, Daniel C; Goodman, Spencer M; Morozko, Eva L; Cole, Stacey M; Boukhvalova, Alexandra K; Skidmore, Jennifer; Syam, Diana; Wilson, Elizabeth A; Fitzgerald, Tracy; Rehman, Atteeq U; Martin, Donna M; Boger, Erich T; Belyantseva, Inna A; Friedman, Thomas B

    2017-02-01

    Protein-protein interactions (PPIs) regulate assembly of macromolecular complexes, yet remain challenging to study within the native cytoplasm where they normally exert their biological effect. Here we miniaturize the concept of affinity pulldown, a gold-standard in vitro PPI interrogation technique, to perform nanoscale pulldowns (NanoSPDs) within living cells. NanoSPD hijacks the normal process of intracellular trafficking by myosin motors to forcibly pull fluorescently tagged protein complexes along filopodial actin filaments. Using dual-color total internal reflection fluorescence microscopy, we demonstrate complex formation by showing that bait and prey molecules are simultaneously trafficked and actively concentrated into a nanoscopic volume at the tips of filopodia. The resulting molecular traffic jams at filopodial tips amplify fluorescence intensities and allow PPIs to be interrogated using standard epifluorescence microscopy. A rigorous quantification framework and software tool are provided to statistically evaluate NanoSPD data sets. We demonstrate the capabilities of NanoSPD for a range of nuclear and cytoplasmic PPIs implicated in human deafness, in addition to dissecting these interactions using domain mapping and mutagenesis experiments. The NanoSPD methodology is extensible for use with other fluorescent molecules, in addition to proteins, and the platform can be easily scaled for high-throughput applications.

  19. Myosin-V: a class of unconventional molecular motors.

    PubMed

    Larson, R E

    1996-03-01

    In this review we focus on the biochemical and structural properties of the myosin-V class of unconventional myosins as an example of the diversity of molecular motors within the myosin superfamily. A member of this class was first identified as a novel calmodulin-binding protein in mammalian brain (Larson RE, Pitta DE and Ferro JA (1988). Brazilian Journal of Medical and Biological Research, 21: 213-217). To date, the myosin-V class is represented by two molecules from yeast, one from nematodes, several from vertebrates (chickens, rats, mice and humans) and possibly one from plants. The domain structure of these myosins features a highly conserved head containing the ATP-hydrolysis and actin-binding sites, an extended neck composed of six tandem IQ-motifs which are sites for calmodulin binding and a large tail which has coiled-coil segments intercalated with globular regions of as yet unknown function. Biochemical studies on purified myosin-V from vertebrate brains and the description of myosin-V mutants in yeast and mice have made myosin-V one of the best characterized, unconventional myosin classes at the present time, surpassed only by the well-studied myosin-I class.

  20. Molecular motors robustly drive active gels to a critically connected state

    NASA Astrophysics Data System (ADS)

    Alvarado, José; Sheinman, Michael; Sharma, Abhinav; Mackintosh, Fred C.; Koenderink, Gijsje H.

    2013-09-01

    Living systems naturally exhibit internal driving: active, molecular processes drive non-equilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, in which molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behaviour occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we developed a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.

  1. Construction of a Chassis for a Tripartite Protein-Based Molecular Motor.

    PubMed

    Small, Lara S R; Bruning, Marc; Thomson, Andrew R; Boyle, Aimee L; Davies, Roberta B; Curmi, Paul M G; Forde, Nancy R; Linke, Heiner; Woolfson, Derek N; Bromley, Elizabeth H C

    2017-03-14

    Improving our understanding of biological motors, both to fully comprehend their activities in vital processes, and to exploit their impressive abilities for use in bionanotechnology, is highly desirable. One means of understanding these systems is through the production of synthetic molecular motors. We demonstrate the use of orthogonal coiled-coil dimers (including both parallel and antiparallel coiled coils) as a hub for linking other components of a previously described synthetic molecular motor, the Tumbleweed. We use circular dichroism, analytical ultracentrifugation, dynamic light scattering, and disulfide rearrangement studies to demonstrate the ability of this six-peptide set to form the structure designed for the Tumbleweed motor. The successful formation of a suitable hub structure is both a test of the transferability of design rules for protein folding as well as an important step in the production of a synthetic protein-based molecular motor.

  2. How molecular motors are arranged on a cargo is important for vesicular transport.

    PubMed

    Erickson, Robert P; Jia, Zhiyuan; Gross, Steven P; Yu, Clare C

    2011-05-01

    The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

  3. Chiral Hydrogen Bond Environment Providing Unidirectional Rotation in Photoactive Molecular Motors.

    PubMed

    García-Iriepa, Cristina; Marazzi, Marco; Zapata, Felipe; Valentini, Alessio; Sampedro, Diego; Frutos, Luis Manuel

    2013-05-02

    Generation of a chiral hydrogen bond environment in efficient molecular photoswitches is proposed as a novel strategy for the design of photoactive molecular motors. Here, the following strategy is used to design a retinal-based motor presenting singular properties: (i) a single excitation wavelength is needed to complete the unidirectional rotation process (360°); (ii) the absence of any thermal step permits the process to take place at low temperatures; and (iii) the ultrafast process permits high rotational frequencies.

  4. Enhanced Diffusion of Molecular Motors in the Presence of Adenosine Triphosphate and External Force

    NASA Astrophysics Data System (ADS)

    Shinagawa, Ryota; Sasaki, Kazuo

    2016-06-01

    The diffusion of a molecular motor in the presence of a constant external force is considered on the basis of a simple theoretical model. The motor is represented by a Brownian particle moving in a series of parabolic potentials placed periodically on a line, and the potential is switched stochastically from one parabola to another by a chemical reaction, which corresponds to the hydrolysis or synthesis of adenosine triphosphate (ATP) in motor proteins. It is found that the diffusion coefficient as a function of the force exhibits peaks. The mechanism of this diffusion enhancement and the possibility of observing it in F1-ATPase, a biological rotary motor, are discussed.

  5. Differential screening of mutated SOD1 transgenic mice reveals early up-regulation of a fast axonal transport component in spinal cord motor neurons.

    PubMed

    Dupuis, L; de Tapia, M; René, F; Lutz-Bucher, B; Gordon, J W; Mercken, L; Pradier, L; Loeffler, J P

    2000-08-01

    In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly(86) to Arg (G86R) mutation equivalent to that found in a subset of human FALS. Using an optimized suppression subtractive hybridization method, a cDNA specifically up-regulated during the asymptomatic phase in the lumbar spinal cord of G86R mice was identified by sequence analysis as the KIF3-associated protein (KAP3), a regulator of fast axonal transport. RT-PCR analysis revealed that KAP3 induction was an early event arising long before axonal degeneration. Immunohistochemical studies further revealed that KAP3 protein predominantly accumulates in large motor neurons of the ventral spinal cord. We further demonstrated that KAP3 up-regulation occurs independent of any change in the other components of the kinesin II complex. However, since the ubiquitous KIF1A motor is up-regulated, our results show an early and complex rearrangement of the fast axonal transport machinery in the course of FALS pathology.

  6. Transport dynamics of molecular motors that switch between an active and inactive state.

    PubMed

    Pinkoviezky, I; Gov, N S

    2013-08-01

    Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.

  7. Towards dynamic control of wettability by using functionalized altitudinal molecular motors on solid surfaces.

    PubMed

    London, Gábor; Chen, Kuang-Yen; Carroll, Gregory T; Feringa, Ben L

    2013-08-05

    We report the synthesis of altitudinal molecular motors that contain functional groups in their rotor part. In an approach to achieve dynamic control over the properties of solid surfaces, a hydrophobic perfluorobutyl chain and a relatively hydrophilic cyano group were introduced to the rotor part of the motors. Molecular motors were attached to quartz surfaces by using interfacial 1,3-dipolar cycloadditions. To test the effect of the functional groups on the rotary motion, photochemical and thermal isomerization studies of the motors were performed both in solution and when attached to the surface. We found that the substituents have no significant effect on the thermal and photochemical processes, and the functionalized motors preserved their rotary function both in solution and on a quartz surface. Preliminary results on the influence of the functional groups on surface wettability are also described.

  8. Computational Design of a Family of Light-Driven Rotary Molecular Motors with Improved Quantum Efficiency.

    PubMed

    Nikiforov, Alexander; Gamez, Jose A; Thiel, Walter; Filatov, Michael

    2016-01-07

    Two new light-driven molecular rotary motors based on the N-alkylated indanylidene benzopyrrole frameworks are proposed and studied using quantum chemical calculations and nonadiabatic molecular dynamics simulations. These new motors perform pure axial rotation, and the photochemical steps of the rotary cycle are dominated by the fast bond-length-alternation motion that enables ultrafast access to the S1/S0 intersection. The new motors are predicted to display a quantum efficiency higher than that of the currently available synthetic all-hydrocarbon motors. Remarkably, the quantum efficiency is not governed by the topography (peaked versus sloped) of the minimum-energy conical intersection, whereas the S1 decay time depends on the topography as well as on the energy of the intersection relative to the S1 minimum. It is the axial chirality (helicity), rather than the point chirality, that controls the sense of rotation of the motor.

  9. Computational Design of a Family of Light-Driven Rotary Molecular Motors with Improved Quantum Efficiency

    PubMed Central

    2015-01-01

    Two new light-driven molecular rotary motors based on the N-alkylated indanylidene benzopyrrole frameworks are proposed and studied using quantum chemical calculations and nonadiabatic molecular dynamics simulations. These new motors perform pure axial rotation, and the photochemical steps of the rotary cycle are dominated by the fast bond-length-alternation motion that enables ultrafast access to the S1/S0 intersection. The new motors are predicted to display a quantum efficiency higher than that of the currently available synthetic all-hydrocarbon motors. Remarkably, the quantum efficiency is not governed by the topography (peaked versus sloped) of the minimum-energy conical intersection, whereas the S1 decay time depends on the topography as well as on the energy of the intersection relative to the S1 minimum. It is the axial chirality (helicity), rather than the point chirality, that controls the sense of rotation of the motor. PMID:26670164

  10. Correlations and symmetry of interactions influence collective dynamics of molecular motors

    NASA Astrophysics Data System (ADS)

    Celis-Garza, Daniel; Teimouri, Hamid; Kolomeisky, Anatoly B.

    2015-04-01

    Enzymatic molecules that actively support many cellular processes, including transport, cell division and cell motility, are known as motor proteins or molecular motors. Experimental studies indicate that they interact with each other and they frequently work together in large groups. To understand the mechanisms of collective behavior of motor proteins we study the effect of interactions in the transport of molecular motors along linear filaments. It is done by analyzing a recently introduced class of totally asymmetric exclusion processes that takes into account the intermolecular interactions via thermodynamically consistent approach. We develop a new theoretical method that allows us to compute analytically all dynamic properties of the system. Our analysis shows that correlations play important role in dynamics of interacting molecular motors. Surprisingly, we find that the correlations for repulsive interactions are weaker and more short-range than the correlations for the attractive interactions. In addition, it is shown that symmetry of interactions affect dynamic properties of molecular motors. The implications of these findings for motor proteins transport are discussed. Our theoretical predictions are tested by extensive Monte Carlo computer simulations.

  11. Exclusion and Hierarchy of Time Scales Lead to Spatial Segregation of Molecular Motors in Cellular Protrusions

    NASA Astrophysics Data System (ADS)

    Pinkoviezky, I.; Gov, N. S.

    2017-01-01

    Molecular motors that carry cargo along biopolymer filaments within cells play a crucial role in the functioning of the cell. In particular, these motors are essential for the formation and maintenance of the cellular protrusions that play key roles in motility and specific functionalities, such as the stereocilia in hair cells. Typically, there are several species of motors, carrying different cargos, that share the same track. Furthermore, it was observed that in the mature stereocilia, the different motors occupy well-segregated bands as a function of distance from the tip. We use a totally asymmetric exclusion process model with two- and three-motor species, to study the conditions that give rise to such spatial patterns. We find that the well-segregated bands appear for motors with a strong hierarchy of attachment or detachment rates. This is a striking example of pattern formation in nonequilibrium, low-dimensional systems.

  12. Exclusion and Hierarchy of Time Scales Lead to Spatial Segregation of Molecular Motors in Cellular Protrusions.

    PubMed

    Pinkoviezky, I; Gov, N S

    2017-01-06

    Molecular motors that carry cargo along biopolymer filaments within cells play a crucial role in the functioning of the cell. In particular, these motors are essential for the formation and maintenance of the cellular protrusions that play key roles in motility and specific functionalities, such as the stereocilia in hair cells. Typically, there are several species of motors, carrying different cargos, that share the same track. Furthermore, it was observed that in the mature stereocilia, the different motors occupy well-segregated bands as a function of distance from the tip. We use a totally asymmetric exclusion process model with two- and three-motor species, to study the conditions that give rise to such spatial patterns. We find that the well-segregated bands appear for motors with a strong hierarchy of attachment or detachment rates. This is a striking example of pattern formation in nonequilibrium, low-dimensional systems.

  13. Mechanism of cooperative behaviour in systems of slow and fast molecular motors.

    PubMed

    Larson, Adam G; Landahl, Eric C; Rice, Sarah E

    2009-06-28

    Two recent theoretical advances have described cargo transport by multiple identical motors and by multiple oppositely directed, but otherwise identical motors [M. J. Muller, S. Klumpp and R. Lipowsky, Proc. Natl. Acad. Sci. U. S. A., 2008, 105(12), 4609-4614; S. Klumpp and R. Lipowsky, Proc. Natl. Acad. Sci. U. S. A., 2005, 102(48), 17284-17289]. Here, we combine a similar theoretical approach with a simple experiment to describe the behaviour of a system comprised of slow and fast molecular motors having the same directionality. We observed the movement of microtubules by mixtures of slow and fast kinesin motors attached to a glass coverslip in a classic sliding filament assay. The motors are identical, except that the slow ones contain five point mutations that collectively reduce their velocity approximately 15-fold without compromising maximal ATPase activity. Our results indicate that a small fraction of fast motors are able to accelerate the dissociation of slow motors from microtubules. Because of this, a sharp, highly cooperative transition occurs from slow to fast microtubule movement as the relative number of fast motors in the assay is increased. Microtubules move at half-maximal velocity when only 15% of the motors in the assay are fast. Our model indicates that this behaviour depends primarily on the relative motor velocities and the asymmetry between their forward and backward dissociation forces. It weakly depends on the number of motors and their processivity. We predict that movement of cargoes bound to two types of motors having very different velocities will be dominated by one or the other motor. Therefore, cargoes can potentially undergo abrupt changes in movement in response to regulatory mechanisms acting on only a small fraction of motors.

  14. Pattern Formations in Polymer-Molecular Motor Networks

    NASA Astrophysics Data System (ADS)

    Smith, David; Humphrey, David; Duggan, Cynthia; Käs, Josef

    2001-03-01

    In previous studies with the microtubule-kinesin system, organized patterns such as asters and rotating vortices have been seen (Nedelec et al, Nature 1997), which were of a dynamic nature and dependent on active motors. A similar system was constructed using actin and myosin, which displays similar patterns, however, with drastically different dynamics. These patterns arise independent of the initial amount of immediate use energy (in the form of ATP), assembling only upon the near exhaustion of available ATP. Further studies have clearly shown that in fact these patterns are not dependent upon the motor activity of the myosin but its propensity to serve as a cross-linking element in an actin network, with the motor activity serving to prevent the arising of order in the system. We believe the dynamic differences inherent between the two polymer-motor systems studied lies primarily in the structural nature of the motor complexes, with the kinesin complex ordering the system by pushing multiple filaments in a parallel direction, and the myosin complexes disordering the system by pushing filaments in an antiparallel manner.

  15. Kinetic Mechanism of DNA Translocation by the RSC Molecular Motor

    PubMed Central

    Eastlund, Allen; Malik, Shuja Shafi; Fischer, Christopher J.

    2013-01-01

    ATP-dependent nucleosome repositioning by chromatin remodeling enzymes requires the translocation of these enzymes along the nucleosomal DNA. Using a fluorescence stopped-flow assay we monitored DNA translocation by a minimal RSC motor and through global analysis of these time courses we have determined that this motor has a macroscopic translocation rate of 2.9 bp/s with a step size of 1.24 bp. From the complementary quantitative analysis of the associated time courses of ATP consumption during DNA translocation we have determined that this motor has an efficiency of 3.0 ATP/bp, which is slightly less that the efficiency observed for several genetically related DNA helicases and which likely results from random pausing by the motor during translocation. Nevertheless, this motor is able to exert enough force during translocation to displace streptavidin from biotinylated DNA. Taken together these results are the necessary first step for quantifying both the role of DNA translocation in nucleosome repositioning by RSC and the efficiency at which RSC couples ATP binding and hydrolysis to nucleosome repositioning. PMID:23399434

  16. Molecular motors pulling cargos in the viscoelastic cytosol: how power strokes beat subdiffusion.

    PubMed

    Goychuk, Igor; Kharchenko, Vasyl O; Metzler, Ralf

    2014-08-21

    The discovery of anomalous diffusion of larger biopolymers and submicron tracers such as endogenous granules, organelles, or virus capsids in living cells, attributed to the viscoelastic nature of the cytoplasm, provokes the question whether this complex environment equally impacts the active intracellular transport of submicron cargos by molecular motors such as kinesins: does the passive anomalous diffusion of free cargo always imply its anomalously slow active transport by motors, the mean transport distance along microtubule growing sublinearly rather than linearly in time? Here we analyze this question within the widely used two-state Brownian ratchet model of kinesin motors based on the continuous-state diffusion along microtubules driven by a flashing binding potential, where the cargo particle is elastically attached to the motor. Depending on the cargo size, the loading force, the amplitude of the binding potential, the turnover frequency of the molecular motor enzyme, and the linker stiffness we demonstrate that the motor transport may turn out either normal or anomalous, as indeed measured experimentally. We show how a highly efficient normal active transport mediated by motors may emerge despite the passive anomalous diffusion of the cargo, and study the intricate effects of the elastic linker. Under different, well specified conditions the microtubule-based motor transport becomes anomalously slow and thus significantly less efficient.

  17. In silico design and testing of guiding tracks for molecular shuttles powered by kinesin motors.

    PubMed

    Nitta, Takahiro; Tanahashi, Akihito; Hirano, Motohisa

    2010-06-07

    We present an extended computer simulation method which allows in silico design and testing of guiding tracks for molecular shuttles powered by kinesin motors. The simulation reproduced molecular shuttle movements under external forces and dissociation of shuttles from guiding track surfaces. The simulation was validated by comparing the simulation results with the corresponding experimental ones. Using the simulation, track designers can change guiding track designs, choose guiding methods, tune the strength of external forces, and test the module performance. This simulation would significantly reduce the effort expended in designing guiding tracks for molecular shuttles powered by kinesin motors.

  18. Molecular motors: how to make models that can be used to convey the concept of molecular ratchets and thermal capture.

    PubMed

    DoHarris, Lindsay; Giesler, Amanda; Humber, Brent; Sukumar, Aravin; Janssen, Luke J

    2011-06-01

    A wide variety of cellular processes use molecular motors, including processive motors that move along some form of track (e.g., myosin with actin, kinesin or dynein with tubulin) and polymerases that move along a template (e.g., DNA and RNA polymerases, ribosomes). In trying to understand how these molecular motors actually move, many apply their understanding of how man-made motors work: the latter use some form of energy to exert a force or torque on its load. However, quite a different mechanism has been proposed to possibly account for the movement of molecular motors. Rather than hydrolyzing ATP to push or pull their load, they might use their own thermal vibrational energy as well as that of their load and their environment to move the load, capturing those movements that occur along a desired vector or axis and resisting others; ATP hydrolysis is required to make backward movements impossible. This intriguing thermal capture or Brownian ratchet model is relatively more difficult to convey to students. In this report, we describe several teaching aids that are very easily constructed using widely available household materials to convey the concept of a molecular ratchet.

  19. Intrinsic irreversibility limits the efficiency of multidimensional molecular motors

    NASA Astrophysics Data System (ADS)

    Jack, M. W.; Tumlin, C.

    2016-05-01

    We consider the efficiency limits of Brownian motors able to extract work from the temperature difference between reservoirs or from external thermodynamic forces. These systems can operate in a variety of modes, including as isothermal engines, heat engines, refrigerators, and heat pumps. We derive analytical results showing that certain classes of multidimensional Brownian motor, including the Smoluchowski-Feynman ratchet, are unable to attain perfect efficiency (Carnot efficiency for heat engines). This demonstrates the presence of intrinsic irreversibilities in their operating mechanism. We present numerical simulations showing that in some cases the loss process that limits efficiency is associated with vortices in the probability current.

  20. How molecular motors work in the crowded environment of living cells: coexistence and efficiency of normal and anomalous transport.

    PubMed

    Goychuk, Igor; Kharchenko, Vasyl O; Metzler, Ralf

    2014-01-01

    Recent experiments reveal both passive subdiffusion of various nanoparticles and anomalous active transport of such particles by molecular motors in the molecularly crowded environment of living biological cells. Passive and active microrheology reveals that the origin of this anomalous dynamics is due to the viscoelasticity of the intracellular fluid. How do molecular motors perform in such a highly viscous, dissipative environment? Can we explain the observed co-existence of the anomalous transport of relatively large particles of 100 to 500 nm in size by kinesin motors with the normal transport of smaller particles by the same molecular motors? What is the efficiency of molecular motors in the anomalous transport regime? Here we answer these seemingly conflicting questions and consistently explain experimental findings in a generalization of the well-known continuous diffusion model for molecular motors with two conformational states in which viscoelastic effects are included.

  1. Increased speed of rotation for the smallest light-driven molecular motor.

    PubMed

    ter Wiel, Matthijs K J; van Delden, Richard A; Meetsma, Auke; Feringa, Ben L

    2003-12-10

    In this paper we present the smallest artificial light-driven molecular motor consisting of only 28 carbon and 24 hydrogen atoms. The concept of controlling directionality of rotary movement at the molecular level by introduction of a stereogenic center next to the central olefinic bond of a sterically overcrowded alkene does not only hold for molecular motors with six-membered rings, but is also applicable to achieve the unidirectional movement for molecular motors having five-membered rings. Although X-ray analyses show that the five-membered rings in the cis- and trans-isomer of the new molecular motor are nearly flat, the energy differences between the (pseudo-)diaxial and (pseudo-)diequatorial conformations of the methyl substituents in both isomers are still large enough to direct the rotation of one-half of the molecule with respect to the other half in a clockwise fashion. The full rotary cycle comprises four consecutive steps: two photochemical isomerizations each followed by a thermal helix inversion. Both photochemical cis-trans isomerizations proceed with a preference for the unstable diequatorial isomers over the stable diaxial isomers. The thermal barriers for helix inversion of this motor molecule have decreased dramatically compared to its six-membered ring analogue, the half-life of the fastest step being only 18 s at room temperature.

  2. Interplay between crosslinkers and dynamic molecular motor-induced instabilities in the moderation of biopolymer organization

    NASA Astrophysics Data System (ADS)

    Smith, David; Humphrey, David; Ziebert, Falko; Zimmermann, Walter; Käs, Josef

    2006-03-01

    Structure and function of biological cells rely on the highly-dynamic self-organization of protein filaments to an intracellular cytoskeleton responsive to mechanical and chemical stimuli. While dissolving these complex cellular structures through Brownian motion is inherently slow (tens of minutes), changes in the activity of the molecular motor myosin II cause rapid order-disorder transitions within 1-2 minutes in reconstituted cytoskeletal actin networks. When motor-induced filament sliding decreases, actin network structure rapidly and reversibly self-organizes into various assemblies triggered by a nonlinear instability. Modulation of static crosslinker concentrations allow for a wide phase space of order ranging from nematics to compact asters & dense packing of motor-filament clusters. The observed isothermal transitions between disorder and self-organization illustrate that molecular motors can substantially contribute to dynamic cellular organization.

  3. Tug-of-war between opposing molecular motors explains chromosomal oscillation during mitosis.

    PubMed

    Sutradhar, S; Paul, R

    2014-03-07

    Chromosomes move towards and away from the centrosomes during the mitosis. This oscillation is observed when the kinetochore, a specific protein structure on the chromosome is captured by centrosome-nucleated polymer called microtubules. We present a computational model, incorporating activities of various molecular motors and microtubule dynamics, to demonstrate the observed oscillation. The model is robust and is not restricted to any particular cell type. Quantifying the average velocity, amplitude and periodicity of the chromosomal oscillation, we compare numerical results with the available experimental data. Our analysis supports a tug-of-war like mechanism between opposing motors that changes the course of chromosomal oscillation. It turns out that, various modes of oscillation can be fully understood by assembling the dynamics of molecular motors. Near the stall regime, when opposing motors are engaged in a tug-of-war, sufficiently large kinetochore-microtubule generated force may prolong the stall durations.

  4. Motility States of Molecular Motors Engaged in a Stochastic Tug-of-War

    NASA Astrophysics Data System (ADS)

    Müller, Melanie J. I.; Klumpp, Stefan; Lipowsky, Reinhard

    2008-12-01

    Intracellular transport is mediated by molecular motors that pull cargos along cytoskeletal filaments. Many cargos move bidirectionally and are transported by two teams of motors which move into opposite directions along the filament. We have recently introduced a stochastic tug-of-war model for this situation. This model describes the motion of the cargo as a Markov process on a two-dimensional state space defined by the numbers of active plus and active minus motors. In spite of its simplicity, this tug-of-war model leads to a complex dependence of the cargo motility on the motor parameters. We present new numerical results for the dependence on the number of involved motors. In addition, we derive a simple and intuitive sharp maxima approximation, from which one obtains the cargo motility state from only four simple inequalities. This approach provides a fast and reliable method to determine the cargo motility.

  5. Future challenges in single-molecule fluorescence and laser trap approaches to studies of molecular motors.

    PubMed

    Elting, Mary Williard; Spudich, James A

    2012-12-11

    Single-molecule analysis is a powerful modern form of biochemistry, in which individual kinetic steps of a catalytic cycle of an enzyme can be explored in exquisite detail. Both single-molecule fluorescence and single-molecule force techniques have been widely used to characterize a number of protein systems. We focus here on molecular motors as a paradigm. We describe two areas where we expect to see exciting developments in the near future: first, characterizing the coupling of force production to chemical and mechanical changes in motors, and second, understanding how multiple motors work together in the environment of the cell.

  6. Stepping and Crowding of Molecular Motors: Statistical Kinetics from an Exclusion Process Perspective

    PubMed Central

    Ciandrini, Luca; Romano, M. Carmen; Parmeggiani, Andrea

    2014-01-01

    Motor enzymes are remarkable molecular machines that use the energy derived from the hydrolysis of a nucleoside triphosphate to generate mechanical movement, achieved through different steps that constitute their kinetic cycle. These macromolecules, nowadays investigated with advanced experimental techniques to unveil their molecular mechanisms and the properties of their kinetic cycles, are implicated in many biological processes, ranging from biopolymerization (e.g., RNA polymerases and ribosomes) to intracellular transport (motor proteins such as kinesins or dyneins). Although the kinetics of individual motors is well studied on both theoretical and experimental grounds, the repercussions of their stepping cycle on the collective dynamics still remains unclear. Advances in this direction will improve our comprehension of transport process in the natural intracellular medium, where processive motor enzymes might operate in crowded conditions. In this work, we therefore extend contemporary statistical kinetic analysis to study collective transport phenomena of motors in terms of lattice gas models belonging to the exclusion process class. Via numerical simulations, we show how to interpret and use the randomness calculated from single particle trajectories in crowded conditions. Importantly, we also show that time fluctuations and non-Poissonian behavior are intrinsically related to spatial correlations and the emergence of large, but finite, clusters of comoving motors. The properties unveiled by our analysis have important biological implications on the collective transport characteristics of processive motor enzymes in crowded conditions. PMID:25185553

  7. Self-organization of waves and pulse trains by molecular motors in cellular protrusions.

    PubMed

    Yochelis, A; Ebrahim, S; Millis, B; Cui, R; Kachar, B; Naoz, M; Gov, N S

    2015-09-03

    Actin-based cellular protrusions are an ubiquitous feature of cells, performing a variety of critical functions ranging from cell-cell communication to cell motility. The formation and maintenance of these protrusions relies on the transport of proteins via myosin motors, to the protrusion tip. While tip-directed motion leads to accumulation of motors (and their molecular cargo) at the protrusion tip, it is observed that motors also form rearward moving, periodic and isolated aggregates. The origins and mechanisms of these aggregates, and whether they are important for the recycling of motors, remain open puzzles. Motivated by novel myosin-XV experiments, a mass conserving reaction-diffusion-advection model is proposed. The model incorporates a non-linear cooperative interaction between motors, which converts them between an active and an inactive state. Specifically, the type of aggregate formed (traveling waves or pulse-trains) is linked to the kinetics of motors at the protrusion tip which is introduced by a boundary condition. These pattern selection mechanisms are found not only to qualitatively agree with empirical observations but open new vistas to the transport phenomena by molecular motors in general.

  8. Stepping and crowding of molecular motors: statistical kinetics from an exclusion process perspective.

    PubMed

    Ciandrini, Luca; Romano, M Carmen; Parmeggiani, Andrea

    2014-09-02

    Motor enzymes are remarkable molecular machines that use the energy derived from the hydrolysis of a nucleoside triphosphate to generate mechanical movement, achieved through different steps that constitute their kinetic cycle. These macromolecules, nowadays investigated with advanced experimental techniques to unveil their molecular mechanisms and the properties of their kinetic cycles, are implicated in many biological processes, ranging from biopolymerization (e.g., RNA polymerases and ribosomes) to intracellular transport (motor proteins such as kinesins or dyneins). Although the kinetics of individual motors is well studied on both theoretical and experimental grounds, the repercussions of their stepping cycle on the collective dynamics still remains unclear. Advances in this direction will improve our comprehension of transport process in the natural intracellular medium, where processive motor enzymes might operate in crowded conditions. In this work, we therefore extend contemporary statistical kinetic analysis to study collective transport phenomena of motors in terms of lattice gas models belonging to the exclusion process class. Via numerical simulations, we show how to interpret and use the randomness calculated from single particle trajectories in crowded conditions. Importantly, we also show that time fluctuations and non-Poissonian behavior are intrinsically related to spatial correlations and the emergence of large, but finite, clusters of comoving motors. The properties unveiled by our analysis have important biological implications on the collective transport characteristics of processive motor enzymes in crowded conditions.

  9. Motor properties from persistence: a linear molecular walker lacking spatial and temporal asymmetry

    NASA Astrophysics Data System (ADS)

    Zuckermann, Martin J.; Angstmann, Christopher N.; Schmitt, Regina; Blab, Gerhard A.; Bromley, Elizabeth HC; Forde, Nancy R.; Linke, Heiner; Curmi, Paul MG

    2015-05-01

    The stepping direction of linear molecular motors is usually defined by a spatial asymmetry of the motor, its track, or both. Here we present a model for a molecular walker that undergoes biased directional motion along a symmetric track in the presence of a temporally symmetric chemical cycle. Instead of using asymmetry, directionality is achieved by persistence. At small load force the walker can take on average thousands of steps in a given direction until it stochastically reverses direction. We discuss a specific experimental implementation of a synthetic motor based on this design and find, using Langevin and Monte Carlo simulations, that a realistic walker can work against load forces on the order of picoNewtons with an efficiency of ∼18%, comparable to that of kinesin. In principle, the walker can be turned into a permanent motor by externally monitoring the walker’s momentary direction of motion, and using feedback to adjust the direction of a load force. We calculate the thermodynamic cost of using feedback to enhance motor performance in terms of the Shannon entropy, and find that it reduces the efficiency of a realistic motor only marginally. We discuss the implications for natural protein motor performance in the context of the strong performance of this design based only on a thermal ratchet.

  10. Self-organization of waves and pulse trains by molecular motors in cellular protrusions

    PubMed Central

    Yochelis, A.; Ebrahim, S.; Millis, B.; Cui, R.; Kachar, B.; Naoz, M.; Gov, N. S.

    2015-01-01

    Actin-based cellular protrusions are an ubiquitous feature of cells, performing a variety of critical functions ranging from cell-cell communication to cell motility. The formation and maintenance of these protrusions relies on the transport of proteins via myosin motors, to the protrusion tip. While tip-directed motion leads to accumulation of motors (and their molecular cargo) at the protrusion tip, it is observed that motors also form rearward moving, periodic and isolated aggregates. The origins and mechanisms of these aggregates, and whether they are important for the recycling of motors, remain open puzzles. Motivated by novel myosin-XV experiments, a mass conserving reaction-diffusion-advection model is proposed. The model incorporates a non-linear cooperative interaction between motors, which converts them between an active and an inactive state. Specifically, the type of aggregate formed (traveling waves or pulse-trains) is linked to the kinetics of motors at the protrusion tip which is introduced by a boundary condition. These pattern selection mechanisms are found not only to qualitatively agree with empirical observations but open new vistas to the transport phenomena by molecular motors in general. PMID:26335545

  11. Influence of molecular motors on the motion of particles in viscoelastic media.

    PubMed

    Bouzat, Sebastián

    2014-06-01

    We study theoretically and by numerical simulations the motion of particles driven by molecular motors in a viscoelastic medium representing the cell cytoplasm. For this, we consider a generalized Langevin equation coupled to a stochastic stepping dynamics for the motors that takes into account the action of each motor separately. In the absence of motors, the model produces subdiffusive motion of particles characterized by a power-law scaling of the mean square displacement versus the lag time as t^{α}, with 0<α<1, similar to that observed in cells. Our results show how the action of the motors can induce a transition to a superdiffusive regime at large lag times with the characteristics of those found in experiments reported in the literature. We also show that at small lag times, the motors can act as static crosslinkers that slow down the natural subdiffusive transport. An analysis of previously reported experimental data in the relevant time scales provides evidence of this phenomenon. Finally, we study the effect of a harmonic potential representing an optical trap, and we show a way to approach to a macroscopic description of the active transport in cells. This last point stresses the relevance of the molecular motors for generating not only directed motion to specific targets, but also fast diffusivelike random motion.

  12. Muscle activation described with a differential equation model for large ensembles of locally coupled molecular motors.

    PubMed

    Walcott, Sam

    2014-10-01

    Molecular motors, by turning chemical energy into mechanical work, are responsible for active cellular processes. Often groups of these motors work together to perform their biological role. Motors in an ensemble are coupled and exhibit complex emergent behavior. Although large motor ensembles can be modeled with partial differential equations (PDEs) by assuming that molecules function independently of their neighbors, this assumption is violated when motors are coupled locally. It is therefore unclear how to describe the ensemble behavior of the locally coupled motors responsible for biological processes such as calcium-dependent skeletal muscle activation. Here we develop a theory to describe locally coupled motor ensembles and apply the theory to skeletal muscle activation. The central idea is that a muscle filament can be divided into two phases: an active and an inactive phase. Dynamic changes in the relative size of these phases are described by a set of linear ordinary differential equations (ODEs). As the dynamics of the active phase are described by PDEs, muscle activation is governed by a set of coupled ODEs and PDEs, building on previous PDE models. With comparison to Monte Carlo simulations, we demonstrate that the theory captures the behavior of locally coupled ensembles. The theory also plausibly describes and predicts muscle experiments from molecular to whole muscle scales, suggesting that a micro- to macroscale muscle model is within reach.

  13. An enantioselective synthetic route toward second-generation light-driven rotary molecular motors.

    PubMed

    Pijper, Thomas C; Pijper, Dirk; Pollard, Michael M; Dumur, Frédéric; Davey, Stephen G; Meetsma, Auke; Feringa, Ben L

    2010-02-05

    Controlling the unidirectional rotary process of second-generation molecular motors demands access to these motors in their enantiomerically pure form. In this paper, we describe an enantioselective route to three new second-generation light-driven molecular motors. Their synthesis starts with the preparation of an optically active alpha-methoxy-substituted upper-half ketone involving an enzymatic resolution. The subsequent conversion of this ketone to the corresponding hydrazone by treatment with hydrazine led to full racemization. However, conversion to a TBDMS-protected hydrazone by treatment with bis-TBDMS hydrazine, prepared according to a new procedure, proceeds with nearly full retention of the stereochemical integrity. Oxidation of the TBDMS-protected hydrazone and subsequent coupling to a lower-half thioketone followed by recrystallization provided the molecular motors with >99% ee. As these are the first molecular motors that have a methoxy substituent at the stereogenic center, the photochemical and thermal isomerization steps involved in the rotary cycle of one of these new molecules were studied in detail with various spectroscopic techniques.

  14. Ultra-fast force-clamp laser trapping of single molecular motors and DNA binding proteins

    NASA Astrophysics Data System (ADS)

    Capitanio, Marco; Monico, Carina; Vanzi, Francesco; Pavone, Francesco S.

    2013-09-01

    Forces play a fundamental role in a wide array of biological processes, regulating enzymatic activity, kinetics of molecular bonds, and molecular motors mechanics. Single molecule force spectroscopy techniques have enabled the investigation of such processes, but they are inadequate to probe short-lived (millisecond and sub-millisecond) molecular complexes. We developed an ultrafast force-clamp spectroscopy technique that uses a dual trap configuration to apply constant loads to a single intermittently interacting biological polymer and a binding protein. Our system displays a delay of only ˜10 μs between formation of the molecular bond and application of the force and is capable of detecting interactions as short as 100 μs. The force-clamp configuration in which our assay operates allows direct measurements of load-dependence of lifetimes of single molecular bonds. Moreover, conformational changes of single proteins and molecular motors can be recorded with sub-nanometer accuracy and few tens of microseconds of temporal resolution. We demonstrate our technique on molecular motors, using myosin II from fast skeletal muscle and on protein-DNA interaction, specifically on Lactose repressor (LacI). The apparatus is stabilized to less than 1 nm with both passive and active stabilization, allowing resolving specific binding regions along the actin filament and DNA molecule. Our technique extends single-molecule force-clamp spectroscopy to molecular complexes that have been inaccessible up to now, opening new perspectives for the investigation of the effects of forces on biological processes.

  15. A theoretical model of a molecular-motor-powered pump.

    PubMed

    Bull, Joseph L; Hunt, Alan J; Meyhöfer, Edgar

    2005-03-01

    The motion of a cylindrical bead in a fluid contained within a two-dimensional channel is investigated using the boundary element method as a model of a biomolecular-motor-powered microfluidics pump. The novelty of the pump lies in the use of motor proteins (kinesin) to power the bead motion and the few moving parts comprising the pump. The performance and feasibility of this pump design is investigated using two model geometries: a straight channel, and a curved channel with two concentric circular walls. In the straight channel geometry, it is shown that increasing the bead radius relative to the channel width, increases the flow rate at the expense of increasing the force the kinesins must generate in order to move the bead. Pump efficiency is generally higher for larger bead radii, and larger beads can support higher imposed loads. In the circular channel geometry, it is shown that bead rotation modifies the force required to move the bead and that shifting the bead inward slightly reduces the required force. Bead rotation has a minimal effect on flow rate. Recirculation regions, which can develop between the bead and the channel walls, influence the stresses and force on the bead. These results suggest this pump design is feasible, and the kinesin molecules provide sufficient force to deliver pico- to atto- l/s flows.

  16. Bidirectional transport by molecular motors: enhanced processivity and response to external forces.

    PubMed

    Müller, Melanie J I; Klumpp, Stefan; Lipowsky, Reinhard

    2010-06-02

    Intracellular transport along cytoskeletal filaments is often mediated by two teams of molecular motors that pull on the same cargo and move in opposite directions along the filaments. We have recently shown theoretically that this bidirectional transport can be understood as a stochastic tug-of-war between the two motor teams. Here, we further develop our theory to investigate the experimentally accessible dynamic behavior of cargos transported by strong motors such as kinesin-1 or cytoplasmic dynein. By studying the run and binding times of such a cargo, we show that the properties of biological motors, such as the large ratio of stall/detachment force and the small ratio of superstall backward/forward velocity, are favorable for bidirectional cargo transport, leading to fast motion and enhanced diffusion. In addition, cargo processivity is shown to be strongly enhanced by transport via several molecular motors even if these motors are engaged in a tug-of-war. Finally, we study the motility of a bidirectional cargo under force. Frictional forces arising, e.g., from the viscous cytoplasm, lead to peaks in the velocity distribution, while external forces as exerted, e.g., by an optical trap, lead to hysteresis effects. Our results, in particular our explicit expressions for the cargo binding time and the distance of the peaks in the velocity relation under friction, are directly accessible to in vitro as well as in vivo experiments.

  17. Bounds and phase diagram of efficiency at maximum power for tight-coupling molecular motors.

    PubMed

    Tu, Z C

    2013-02-01

    The efficiency at maximum power (EMP) for tight-coupling molecular motors is investigated within the framework of irreversible thermodynamics. It is found that the EMP depends merely on the constitutive relation between the thermodynamic current and force. The motors are classified into four generic types (linear, superlinear, sublinear, and mixed types) according to the characteristics of the constitutive relation, and then the corresponding ranges of the EMP for these four types of molecular motors are obtained. The exact bounds of the EMP are derived and expressed as the explicit functions of the free energy released by the fuel in each motor step. A phase diagram is constructed which clearly shows how the region where the parameters (the load distribution factor and the free energy released by the fuel in each motor step) are located can determine whether the value of the EMP is larger or smaller than 1/2. This phase diagram reveals that motors using ATP as fuel under physiological conditions can work at maximum power with higher efficiency (> 1/2) for a small load distribution factor (< 0.1).

  18. Beam finite-element model of a molecular motor for the simulation of active fibre networks

    PubMed Central

    Müller, Kei W.; Birzle, Anna M.; Wall, Wolfgang A.

    2016-01-01

    Molecular motors are proteins that excessively increase the efficiency of subcellular transport processes. They allow for cell division, nutrient transport and even macroscopic muscle movement. In order to understand the effect of motors in large biopolymer networks, e.g. the cytoskeleton, we require a suitable model of a molecular motor. In this contribution, we present such a model based on a geometrically exact beam finite-element formulation. We discuss the numerical model of a non-processive motor such as myosin II, which interacts with actin filaments. Based on experimental data and inspired by the theoretical understanding offered by the power-stroke model and the swinging-cross-bridge model, we parametrize our numerical model in order to achieve the effect that a physiological motor has on its cargo. To this end, we introduce the mechanical and mathematical foundations of the model, then discuss its calibration, prove its usefulness by conducting finite-element simulations of actin–myosin motility assays and assess the influence of motors on the rheology of semi-flexible biopolymer networks. PMID:26997891

  19. Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors.

    PubMed

    Johann, D; Goswami, D; Kruse, K

    2016-06-01

    During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.

  20. Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors

    NASA Astrophysics Data System (ADS)

    Johann, D.; Goswami, D.; Kruse, K.

    2016-06-01

    During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.

  1. Effective rates from thermodynamically consistent coarse-graining of models for molecular motors with probe particles.

    PubMed

    Zimmermann, Eva; Seifert, Udo

    2015-02-01

    Many single-molecule experiments for molecular motors comprise not only the motor but also large probe particles coupled to it. The theoretical analysis of these assays, however, often takes into account only the degrees of freedom representing the motor. We present a coarse-graining method that maps a model comprising two coupled degrees of freedom which represent motor and probe particle to such an effective one-particle model by eliminating the dynamics of the probe particle in a thermodynamically and dynamically consistent way. The coarse-grained rates obey a local detailed balance condition and reproduce the net currents. Moreover, the average entropy production as well as the thermodynamic efficiency is invariant under this coarse-graining procedure. Our analysis reveals that only by assuming unrealistically fast probe particles, the coarse-grained transition rates coincide with the transition rates of the traditionally used one-particle motor models. Additionally, we find that for multicyclic motors the stall force can depend on the probe size. We apply this coarse-graining method to specific case studies of the F(1)-ATPase and the kinesin motor.

  2. Force Generation by Molecular-Motor-Powered Microtubule Bundles; Implications for Neuronal Polarization and Growth

    PubMed Central

    Jakobs, Maximilian; Franze, Kristian; Zemel, Assaf

    2015-01-01

    The heavily cross-linked microtubule (MT) bundles found in neuronal processes play a central role in the initiation, growth and maturation of axons and dendrites; however, a quantitative understanding of their mechanical function is still lacking. We here developed computer simulations to investigate the dynamics of force generation in 1D bundles of MTs that are cross-linked and powered by molecular motors. The motion of filaments and the forces they exert are investigated as a function of the motor type (unipolar or bipolar), MT density and length, applied load, and motor connectivity. We demonstrate that only unipolar motors (e.g., kinesin-1) can provide the driving force for bundle expansion, while bipolar motors (e.g., kinesin-5) oppose it. The force generation capacity of the bundles is shown to depend sharply on the fraction of unipolar motors due to a percolation transition that must occur in the bundle. Scaling laws between bundle length, force, MT length and motor fraction are presented. In addition, we investigate the dynamics of growth in the presence of a constant influx of MTs. Beyond a short equilibration period, the bundles grow linearly in time. In this growth regime, the bundle extends as one mass forward with most filaments sliding with the growth velocity. The growth velocity is shown to be dictated by the inward flux of MTs, to inversely scale with the load and to be independent of the free velocity of the motors. These findings provide important molecular-level insights into the mechanical function of the MT cytoskeleton in normal axon growth and regeneration after injury. PMID:26617489

  3. Force Generation by Molecular-Motor-Powered Microtubule Bundles; Implications for Neuronal Polarization and Growth.

    PubMed

    Jakobs, Maximilian; Franze, Kristian; Zemel, Assaf

    2015-01-01

    The heavily cross-linked microtubule (MT) bundles found in neuronal processes play a central role in the initiation, growth and maturation of axons and dendrites; however, a quantitative understanding of their mechanical function is still lacking. We here developed computer simulations to investigate the dynamics of force generation in 1D bundles of MTs that are cross-linked and powered by molecular motors. The motion of filaments and the forces they exert are investigated as a function of the motor type (unipolar or bipolar), MT density and length, applied load, and motor connectivity. We demonstrate that only unipolar motors (e.g., kinesin-1) can provide the driving force for bundle expansion, while bipolar motors (e.g., kinesin-5) oppose it. The force generation capacity of the bundles is shown to depend sharply on the fraction of unipolar motors due to a percolation transition that must occur in the bundle. Scaling laws between bundle length, force, MT length and motor fraction are presented. In addition, we investigate the dynamics of growth in the presence of a constant influx of MTs. Beyond a short equilibration period, the bundles grow linearly in time. In this growth regime, the bundle extends as one mass forward with most filaments sliding with the growth velocity. The growth velocity is shown to be dictated by the inward flux of MTs, to inversely scale with the load and to be independent of the free velocity of the motors. These findings provide important molecular-level insights into the mechanical function of the MT cytoskeleton in normal axon growth and regeneration after injury.

  4. A Hopping Mechanism for Cargo Transport by Molecular Motors on Crowded Microtubules

    NASA Astrophysics Data System (ADS)

    Goldman, Carla

    2010-05-01

    Most models designed to study the bidirectional movement of cargos as they are driven by molecular motors rely on the idea that motors of different polarities can be coordinated by external agents if arranged into a motor-cargo complex to perform the necessary work Gross, Hither and yon: a review of bidirectional microtubule-based transport (Gross in Phys. Biol. 1:R1-R11, 2004). Although these models have provided us with important insights into these phenomena, there are still many unanswered questions regarding the mechanisms through which the movement of the complex takes place on crowded microtubules. For example (i) how does cargo-binding affect motor motility? and in connection with that - (ii) how does the presence of other motors (and also other cargos) on the microtubule affect the motility of the motor-cargo complex? We discuss these questions from a different perspective. The movement of a cargo is conceived here as a hopping process resulting from the transference of cargo between neighboring motors. In the light of this, we examine the conditions under which cargo might display bidirectional movement even if directed by motors of a single polarity. The global properties of the model in the long-time regime are obtained by mapping the dynamics of the collection of interacting motors and cargos into an asymmetric simple exclusion process (ASEP) which can be resolved using the matrix ansatz introduced by Derrida (Derrida and Evans in Nonequilibrium Statistical Mechanics in One Dimension, pp. 277-304, 1997; Derrida et al. in J. Phys. A 26:1493-1517, 1993).

  5. Characterizing the composition of molecular motors on moving axonal cargo using "cargo mapping" analysis.

    PubMed

    Neumann, Sylvia; Campbell, George E; Szpankowski, Lukasz; Goldstein, Lawrence S B; Encalada, Sandra E

    2014-10-30

    Understanding the mechanisms by which molecular motors coordinate their activities to transport vesicular cargoes within neurons requires the quantitative analysis of motor/cargo associations at the single vesicle level. The goal of this protocol is to use quantitative fluorescence microscopy to correlate ("map") the position and directionality of movement of live cargo to the composition and relative amounts of motors associated with the same cargo. "Cargo mapping" consists of live imaging of fluorescently labeled cargoes moving in axons cultured on microfluidic devices, followed by chemical fixation during recording of live movement, and subsequent immunofluorescence (IF) staining of the exact same axonal regions with antibodies against motors. Colocalization between cargoes and their associated motors is assessed by assigning sub-pixel position coordinates to motor and cargo channels, by fitting Gaussian functions to the diffraction-limited point spread functions representing individual fluorescent point sources. Fixed cargo and motor images are subsequently superimposed to plots of cargo movement, to "map" them to their tracked trajectories. The strength of this protocol is the combination of live and IF data to record both the transport of vesicular cargoes in live cells and to determine the motors associated to these exact same vesicles. This technique overcomes previous challenges that use biochemical methods to determine the average motor composition of purified heterogeneous bulk vesicle populations, as these methods do not reveal compositions on single moving cargoes. Furthermore, this protocol can be adapted for the analysis of other transport and/or trafficking pathways in other cell types to correlate the movement of individual intracellular structures with their protein composition. Limitations of this protocol are the relatively low throughput due to low transfection efficiencies of cultured primary neurons and a limited field of view available for

  6. DNA polymerase as a molecular motor and pump.

    PubMed

    Sengupta, Samudra; Spiering, Michelle M; Dey, Krishna K; Duan, Wentao; Patra, Debabrata; Butler, Peter J; Astumian, R Dean; Benkovic, Stephen J; Sen, Ayusman

    2014-03-25

    DNA polymerase is responsible for synthesizing DNA, a key component in the running of biological machinery. Using fluorescence correlation spectroscopy, we demonstrate that the diffusive movement of a molecular complex of DNA template and DNA polymerase enhances during nucleotide incorporation into the growing DNA template. The diffusion coefficient of the complex also shows a strong dependence on its inorganic cofactor, Mg2+ ions. When exposed to gradients of either nucleotide or cofactor concentrations, an ensemble of DNA polymerase complex molecules shows collective movement toward regions of higher concentrations. By immobilizing the molecular complex on a patterned gold surface, we demonstrate the fabrication of DNA polymerase-powered fluid pumps. These miniature pumps are capable of transporting fluid and tracer particles in a directional manner with the pumping speed increasing in the presence of the cofactor. The role of DNA polymerase as a micropump opens up avenues for designing miniature fluid pumps using enzymes as engines.

  7. Embryonic amygdalar transplants in adult rats with motor cortex lesions: a molecular and electrophysiological analysis.

    PubMed

    Jiménez-Díaz, Lydia; Nava-Mesa, Mauricio O; Heredia, Margarita; Riolobos, Adelaida S; Gómez-Álvarez, Marcelo; Criado, José María; de la Fuente, Antonio; Yajeya, Javier; Navarro-López, Juan D

    2011-01-01

    Transplants of embryonic nervous tissue ameliorate motor deficits induced by motor cortex lesions in adult animals. Restoration of lost brain functions has been recently shown in grafts of homotopic cortical origin, to be associated with a functional integration of the transplant after development of reciprocal host-graft connections. Nevertheless little is known about physiological properties or gene expression profiles of cortical implants with functional restorative capacity but no cortical origin. In this study, we show molecular and electrophysiological evidence supporting the functional development and integration of heterotopic transplants of embryonic amygdalar tissue placed into pre-lesioned motor cortex of adult rats. Grafts were analyzed 3 months post-transplantation. Using reverse transcriptase quantitative polymerase chain reaction, we found that key glutamatergic, GABAergic, and muscarinic receptors transcripts were expressed at different quantitative levels both in grafted and host tissues, but were all continuously present in the graft. Parallel sharp electrode recordings of grafted neurons in brain slices showed a regular firing pattern of transplanted neurons similar to host amygdalar pyramidal neurons. Synaptic connections from the adjacent host cortex on grafted neurons were electrophysiologically investigated and confirmed our molecular results. Taken together, our findings indicate that grafted neurons from a non-cortical, non-motor-related, but ontogenetical similar source, not only received functionally effective contacts from the adjacent motor cortex, but also developed electrophysiological and gene expression patterns comparable to host pyramidal neurons; suggesting an interesting tool for the field of neural repair and donor tissue in adults.

  8. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors.

    PubMed

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  9. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors

    NASA Astrophysics Data System (ADS)

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T.; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  10. Light-driven rotary molecular motors without point chirality: a minimal design.

    PubMed

    Wang, Jun; Oruganti, Baswanth; Durbeej, Bo

    2017-03-08

    A fundamental requirement for achieving photoinduced unidirectional rotary motion about an olefinic bond in a molecular motor is that the potential energy surface of the excited state is asymmetric with respect to clockwise and counterclockwise rotations. In most available light-driven rotary molecular motors, such asymmetry is guaranteed by the presence of a stereocenter. Here, we present non-adiabatic molecular dynamics simulations based on multiconfigurational quantum chemistry to demonstrate that this chiral feature is not essential for inducing unidirectional rotary motion in molecules that incorporate a cyclohexenylidene moiety into a protonated Schiff-base framework. Rather, the simulations show that it is possible to exploit the intrinsic asymmetry of the puckered cyclohexenylidene to control the direction of photoinduced rotation.

  11. Memory, bias, and correlations in bidirectional transport of molecular-motor-driven cargoes

    NASA Astrophysics Data System (ADS)

    Bhat, Deepak; Gopalakrishnan, Manoj

    2013-10-01

    Molecular motors are specialized proteins that perform active, directed transport of cellular cargoes on cytoskeletal filaments. In many cases, cargo motion powered by motor proteins is found to be bidirectional, and may be viewed as a biased random walk with fast unidirectional runs interspersed with slow tug-of-war states. The statistical properties of this walk are not known in detail, and here, we study memory and bias, as well as directional correlations between successive runs in bidirectional transport. We show, based on a study of the direction-reversal probabilities of the cargo using a purely stochastic (tug-of-war) model, that bidirectional motion of cellular cargoes is, in general, a correlated random walk. In particular, while the motion of a cargo driven by two oppositely pulling motors is a Markovian random walk, memory of direction appears when multiple motors haul the cargo in one or both directions. In the latter case, the Markovian nature of the underlying single-motor processes is hidden by internal transitions between degenerate run and pause states of the cargo. Interestingly, memory is found to be a nonmonotonic function of the number of motors. Stochastic numerical simulations of the tug-of-war model support our mathematical results and extend them to biologically relevant situations.

  12. Extracting the stepping dynamics of molecular motors in living cells from trajectories of single particles.

    PubMed

    Bruno, Augusto; Bruno, Luciana; Levi, Valeria

    2013-01-01

    Molecular motors are responsible of transporting a wide variety of cargos in the cytoplasm. Current efforts are oriented to characterize the biophysical properties of motors in cells with the aim of elucidating the mechanisms of these nanomachines in the complex cellular environment. In this study, we present an algorithm designed to extract motor step sizes and dwell times between steps from trajectories of motors or cargoes driven by motors in cells. The algorithm is based on finding patterns in the trajectory compatible with the behavior expected for a motor step, i.e., a region of confined motion followed by a jump in the position to another region of confined motion with similar characteristics to the previous one. We show that this algorithm allows the analysis of 2D trajectories even if they present complex motion patterns such as active transport interspersed with diffusion and does not require the assumption of a given step size or dwell period. The confidence on the step detection can be easily obtained and allows the evaluation of the confidence of the dwell and step size distributions. To illustrate the possible applications of this algorithm, we analyzed trajectories of myosin-V driven organelles in living cells.

  13. Gamma-diketone axonopathy: analyses of cytoskeletal motors and highways in CNS myelinated axons.

    PubMed

    Zhang, Lihai; Gavin, Terrence; DeCaprio, Anthony P; LoPachin, Richard M

    2010-09-01

    2,5-Hexanedione (HD) intoxication is associated with axon atrophy that might be responsible for the characteristic gait abnormalities, hindlimb skeletal muscle weakness and other neurological deficits that accompany neurotoxicity. Although previous mechanistic research focused on neurofilament triplet proteins (NFL, NFM, NFH), other cytoskeletal targets are possible. Therefore, to identify potential non-NF protein targets, we characterized the effects of HD on protein-protein interactions in cosedimentation assays using microtubules and NFs prepared from spinal cord of rats intoxicated at different daily dose rates (175 and 400 mg/kg/day). Results indicate that HD did not alter the presence of alpha- or beta-tubulins in these preparations, nor were changes noted in the distribution of either anterograde (KIF1A, KIF3, KIF5) or retrograde (dynein) molecular motors. The cosedimentation of dynactin, a dynein-associated protein, also was not affected. Immunoblot analysis of microtubule-associated proteins (MAPs) in microtubule preparations revealed substantial reductions (45-80%) in MAP1A, MAP1B heavy chain, MAP2, and tau regardless of HD dose rate. MAP1B light chain content was not altered. Finally, HD intoxication did not influence native NF protein content in either preparation. As per previous research, microtubule and NF preparations were enriched in high-molecular weight NF species. However, these NF derivatives were common to both HD and control samples, suggesting a lack of pathognomonic relevance. These data indicate that, although motor proteins were not affected, HD selectively impaired MAP-microtubule binding, presumably through adduction of lysine residues that mediate such interactions. Given their critical role in cytoskeletal physiology, MAPs could represent a relevant target for the induction of gamma-diketone axonopathy.

  14. Stochastic mechano-chemical kinetics of molecular motors: A multidisciplinary enterprise from a physicist’s perspective

    NASA Astrophysics Data System (ADS)

    Chowdhury, Debashish

    2013-08-01

    A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors “transduce” input energy into mechanical work. All the nano-motors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multi-module motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular nano-motors, we consider the porters, sliders and rowers, pistons and hooks, exporters, importers, packers and movers as well as those that also synthesize, manipulate and degrade “macromolecules of life”. We review mostly the quantitative models for the kinetics of these motors. We also describe several of those motor-driven intracellular stochastic processes for which quantitative models are yet to be developed. In part I, we discuss mainly the methodology and the generic models of various important classes of molecular motors. In part II, we review many specific examples emphasizing the unity of the basic mechanisms as well as diversity of operations arising from the differences in their detailed structure and kinetics. Multi-disciplinary research is presented here from the perspective of physicists.

  15. Analysis of persistence during intracellular actin-based transport mediated by molecular motors

    NASA Astrophysics Data System (ADS)

    Pallavicini, C.; Despósito, M. A.; Levi, V.; Bruno, L.

    2010-09-01

    The displacement of particles or probes in the cell cytoplasm as a function of time is characterized by different anomalous diffusion regimes. The transport of large cargoes, such as organelles, vesicles or large proteins, involves the action of ATP-consuming molecular motors. We investigate the motion of pigment organelles driven by myosin-V motors in Xenopus laevis melanocytes using a high spatio-temporal resolution tracking technique. By analyzing the turning angles (phi) of the obtained 2D trajectories as a function of the time lag, we determine the critical time of the transition between anticorrelated and directed motion as the time when the turning angles begin to concentrate around phi = 0. We relate this transition with the crossover from subdiffusive to superdiffusive behavior observed in a previous work [5]. We also assayed the properties of the trajectories in cells with inhibited myosin activity, and we can compare the results in the presence and absence of active motors.

  16. Transition to superdiffusive behavior in intracellular actin-based transport mediated by molecular motors

    NASA Astrophysics Data System (ADS)

    Bruno, L.; Levi, V.; Brunstein, M.; Despósito, M. A.

    2009-07-01

    Intracellular transport of large cargoes, such as organelles, vesicles, or large proteins, is a complex dynamical process that involves the interplay of adenosine triphosphate-consuming molecular motors, cytoskeleton filaments, and the viscoelastic cytoplasm. In this work we investigate the motion of pigment organelles (melanosomes) driven by myosin-V motors in Xenopus laevis melanocytes using a high-spatio-temporal resolution tracking technique. By analyzing the obtained trajectories, we show that the melanosomes mean-square displacement undergoes a transition from a subdiffusive to a superdiffusive behavior. A stochastic theoretical model, which explicitly considers the collective action of the molecular motors, is introduced to generalize the interpretation of our data. Starting from a generalized Langevin equation, we derive an analytical expression for the mean square displacement, which also takes into account the experimental noise. By fitting theoretical expressions to experimental data we were able to discriminate the exponents that characterize the passive and active contributions to the dynamics and to estimate the “global” motor forces correctly. Then, our model gives a quantitative description of active transport in living cells with a reduced number of parameters.

  17. Operations and thermodynamics of an artificial rotary molecular motor in solution.

    PubMed

    Moro, Lorenzo; di Giosia, Matteo; Calvaresi, Matteo; Bakalis, Evangelos; Zerbetto, Francesco

    2014-06-23

    A general framework is provided that makes possible the estimation of time-dependent properties of a stochastic system moving far from equilibrium. The process is investigated and discussed in general terms of nonequilibrium thermodynamics. The approach is simple and can be exploited to gain insight into the dynamics of any molecular-level machine. As a case study, the dynamics of an artificial molecular rotary motor, similar to the inversion of a helix, which drives the motor from a metastable state to equilibrium, are examined. The energy path that the motor walks was obtained from the results of atomistic calculations. The motor undergoes unidirectional rotation and its entropy, internal energy, free energy, and net exerted force are given as a function of time, starting from the solution of Smoluchowski's equation. The rather low value of the organization index, that is, the ratio of the work done by the particle against friction during the unidirectional motion per available free energy, reveals that the motion is mainly subject to randomness, and the amount of energy converted to heat due to the directional motion is very small.

  18. Structural and Molecular Basis for Coordination in a Viral DNA Packaging Motor

    PubMed Central

    Reyes-Aldrete, Emilio; Sherman, Michael B.; Woodson, Michael; Atz, Rockney; Grimes, Shelley; Jardine, Paul J.; Morais, Marc C.

    2016-01-01

    SUMMARY Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA packaging motor in bacteriophage phi29 show how individual subunits are arranged in a pentameric ATPase ring, and suggest how their activities are coordinated to translocate dsDNA. The resulting pseudo-atomic structure of the motor and accompanying functional analyses show how ATP is bound in the ATPase active site; identify two DNA contacts, including a potential DNA translocating loop; demonstrate that a trans-acting arginine finger is involved in coordinating hydrolysis around the ring; and suggest a functional coupling between the arginine finger and the DNA translocating loop. The ability to visualize the motor in action illuminates how the different motor components interact with each other and with their DNA substrate. PMID:26904950

  19. Allosteric Regulation of the Rotational Speed in a Light-Driven Molecular Motor

    PubMed Central

    2016-01-01

    The rotational speed of an overcrowded alkene-based molecular rotary motor, having an integrated 4,5-diazafluorenyl coordination motif, can be regulated allosterically via the binding of metal ions. DFT calculations have been used to predict the relative speed of rotation of three different (i.e., zinc, palladium, and platinum) metal dichloride complexes. The photochemical and thermal isomerization behavior of these complexes has been studied in detail using UV–vis and 1H NMR spectroscopy. Our results confirm that metal coordination induces a contraction of the diazafluorenyl lower half, resulting in a reduction of the steric hindrance in the “fjord” region of the molecule, which causes an increase of the rotational speed. Importantly, metal complexation can be accomplished in situ and is found to be reversible upon the addition of a competing ligand. Consequently, the rotational behavior of these molecular motors can be dynamically controlled with chemical additives. PMID:27669358

  20. Prototypes of molecular motors based on star-shaped organometallic ruthenium complexes.

    PubMed

    Vives, Guillaume; de Rouville, Henri-Pierre Jacquot; Carella, Alexandre; Launay, Jean-Pierre; Rapenne, Gwénaël

    2009-06-01

    This tutorial review presents our strategy to control the rotation in a molecular rotary motor, and the family of star-shaped ruthenium complexes designed to perform such a task. The molecules have a piano-stool structure with a "stator" meant to be grafted on a surface, and a "rotor" bearing redox-active groups, so that addressing the molecule with nano-electrodes would trigger rotation.

  1. How molecular motors extract order from chaos (a key issues review).

    PubMed

    Hoffmann, Peter M

    2016-03-01

    Molecular motors are the workhorses of living cells. Seemingly by 'magic', these molecules are able to complete purposeful tasks while being immersed in a sea of thermal chaos. Here, we review the current understanding of how these machines work, present simple models based on thermal ratchets, discuss implications for statistical physics, and provide an overview of ongoing research in this important and fascinating field of study.

  2. How molecular motors extract order from chaos (a key issues review)

    NASA Astrophysics Data System (ADS)

    Hoffmann, Peter M.

    2016-03-01

    Molecular motors are the workhorses of living cells. Seemingly by ‘magic’, these molecules are able to complete purposeful tasks while being immersed in a sea of thermal chaos. Here, we review the current understanding of how these machines work, present simple models based on thermal ratchets, discuss implications for statistical physics, and provide an overview of ongoing research in this important and fascinating field of study.

  3. Computational Insight to Improve the Thermal Isomerisation Performance of Overcrowded Alkene-Based Molecular Motors through Structural Redesign.

    PubMed

    Oruganti, Baswanth; Wang, Jun; Durbeej, Bo

    2016-11-04

    Synthetic overcrowded alkene-based molecular motors achieve 360° unidirectional rotary motion of one motor half (rotator) relative to the other (stator) through sequential photochemical and thermal isomerisation steps. In order to facilitate and expand the use of these motors for various applications, it is important to investigate ways to increase the rates and efficiencies of the reactions governing the rotary motion. Here, we use computational methods to explore whether the thermal isomerisation performance of some of the fastest available motors of this type can be further improved by reducing the sizes of the motor halves. Presenting three new redesigned motors that combine an indanylidene rotator with a cyclohexadiene, pyran or thiopyran stator, we first use multiconfigurational quantum chemical methods to verify that the photoisomerisations of these motors sustain unidirectional rotary motion. Then, by performing density functional calculations, we identify both stepwise and concerted mechanisms for the thermal isomerisations of the motors and show that the rate-determining free-energy barriers of these processes are up to 25 kJ mol(-1) smaller than those of the original motors. Furthermore, the thermal isomerisations of the redesigned motors proceed in fewer steps. Altogether, the results suggest that the redesigned motors are useful templates for improving the thermal isomerisation performance of existing overcrowded alkene-based motors.

  4. Synthesis of technomimetic molecules: towards rotation control in single-molecular machines and motors.

    PubMed

    Rapenne, Gwénaël

    2005-04-07

    Technomimetic molecules are molecules designed to imitate macroscopic objects at the molecular level, also transposing the motions that these objects are able to undergo. This article focuses on technomimetic molecules with rotary motions, including gears, wheelbarrows and motors. Following the bottom-up approach the synthesis of technomimetic molecules grants access to the study of mechanical properties at the molecular level. These molecules are designed to operate as single molecules on surfaces under the control of the tip of a scanning tunneling microscope or atomic force microscope.

  5. Molecular motor-driven abrupt anisotropic shape change in a single crystal of a Ni complex.

    PubMed

    Yao, Zi-Shuo; Mito, Masaki; Kamachi, Takashi; Shiota, Yoshihito; Yoshizawa, Kazunari; Azuma, Nobuaki; Miyazaki, Yuji; Takahashi, Kazuyuki; Zhang, Kuirun; Nakanishi, Takumi; Kang, Soonchul; Kanegawa, Shinji; Sato, Osamu

    2014-12-01

    Many molecular machines with controllable molecular-scale motors have been developed. However, transmitting molecular movement to the macroscopic scale remains a formidable challenge. Here we report a single crystal of a Ni complex whose shape changes abruptly and reversibly in response to thermal changes at around room temperature. Variable-temperature single-crystal X-ray diffraction studies show that the crystalline shape change is induced by an unusual 90° rotation of uniaxially aligned oxalate molecules. The oxalate dianions behave as molecular-scale rotors, with their movement propagated through the entire crystalline material via intermolecular hydrogen bonding. Consequently, the subnanometre-scale changes in the oxalate molecules are instantly amplified to a micrometre-scale contraction or expansion of the crystal, accompanied by a thermal hysteresis loop. The shape change in the crystal was clearly detected under an optical microscope. The large directional deformation and prompt response suggest a role for this material in microscale or nanoscale thermal actuators.

  6. Molecular motor-driven abrupt anisotropic shape change in a single crystal of a Ni complex

    NASA Astrophysics Data System (ADS)

    Yao, Zi-Shuo; Mito, Masaki; Kamachi, Takashi; Shiota, Yoshihito; Yoshizawa, Kazunari; Azuma, Nobuaki; Miyazaki, Yuji; Takahashi, Kazuyuki; Zhang, Kuirun; Nakanishi, Takumi; Kang, Soonchul; Kanegawa, Shinji; Sato, Osamu

    2014-12-01

    Many molecular machines with controllable molecular-scale motors have been developed. However, transmitting molecular movement to the macroscopic scale remains a formidable challenge. Here we report a single crystal of a Ni complex whose shape changes abruptly and reversibly in response to thermal changes at around room temperature. Variable-temperature single-crystal X-ray diffraction studies show that the crystalline shape change is induced by an unusual 90° rotation of uniaxially aligned oxalate molecules. The oxalate dianions behave as molecular-scale rotors, with their movement propagated through the entire crystalline material via intermolecular hydrogen bonding. Consequently, the subnanometre-scale changes in the oxalate molecules are instantly amplified to a micrometre-scale contraction or expansion of the crystal, accompanied by a thermal hysteresis loop. The shape change in the crystal was clearly detected under an optical microscope. The large directional deformation and prompt response suggest a role for this material in microscale or nanoscale thermal actuators.

  7. Stochastic dynamics of small ensembles of non-processive molecular motors: the parallel cluster model.

    PubMed

    Erdmann, Thorsten; Albert, Philipp J; Schwarz, Ulrich S

    2013-11-07

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes, or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of the fraction of bound motors under load and thus to firm attachment even for small ensembles. This adaptation to load results in a concave force-velocity relation described by a Hill relation. For external load provided by a linear spring, myosin II ensembles dynamically adjust themselves towards an isometric state with constant average position and load. The dynamics of the ensembles is now determined mainly by the distribution of motors over the different kinds of bound states. For increasing stiffness of the external spring, there is a sharp transition beyond which myosin II can no longer perform the power stroke. Slow unbinding from the pre-power-stroke state protects the ensembles against detachment.

  8. Chaperone-enhanced purification of unconventional myosin 15, a molecular motor specialized for stereocilia protein trafficking

    PubMed Central

    Bird, Jonathan E.; Takagi, Yasuharu; Billington, Neil; Strub, Marie-Paule; Sellers, James R.; Friedman, Thomas B.

    2014-01-01

    Unconventional myosin 15 is a molecular motor expressed in inner ear hair cells that transports protein cargos within developing mechanosensory stereocilia. Mutations of myosin 15 cause profound hearing loss in humans and mice; however, the properties of this motor and its regulation within the stereocilia organelle are unknown. To address these questions, we expressed a subfragment 1-like (S1) truncation of mouse myosin 15, comprising the predicted motor domain plus three light-chain binding sites. Following unsuccessful attempts to express functional myosin 15-S1 using the Spodoptera frugiperda (Sf9)-baculovirus system, we discovered that coexpression of the muscle-myosin–specific chaperone UNC45B, in addition to the chaperone heat-shock protein 90 (HSP90) significantly increased the yield of functional protein. Surprisingly, myosin 15-S1 did not bind calmodulin with high affinity. Instead, the IQ domains bound essential and regulatory light chains that are normally associated with class II myosins. We show that myosin 15-S1 is a barbed-end–directed motor that moves actin filaments in a gliding assay (∼430 nm·s−1 at 30 °C), using a power stroke of 7.9 nm. The maximum ATPase rate (kcat ∼6 s−1) was similar to the actin-detachment rate (kdet = 6.2 s−1) determined in single molecule optical trapping experiments, indicating that myosin 15-S1 was rate limited by transit through strongly actin-bound states, similar to other processive myosin motors. Our data further indicate that in addition to folding muscle myosin, UNC45B facilitates maturation of an unconventional myosin. We speculate that chaperone coexpression may be a simple method to optimize the purification of other myosin motors from Sf9 insect cells. PMID:25114250

  9. Stochastic dynamics of small ensembles of non-processive molecular motors: The parallel cluster model

    SciTech Connect

    Erdmann, Thorsten; Albert, Philipp J.; Schwarz, Ulrich S.

    2013-11-07

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes, or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of the fraction of bound motors under load and thus to firm attachment even for small ensembles. This adaptation to load results in a concave force-velocity relation described by a Hill relation. For external load provided by a linear spring, myosin II ensembles dynamically adjust themselves towards an isometric state with constant average position and load. The dynamics of the ensembles is now determined mainly by the distribution of motors over the different kinds of bound states. For increasing stiffness of the external spring, there is a sharp transition beyond which myosin II can no longer perform the power stroke. Slow unbinding from the pre-power-stroke state protects the ensembles against detachment.

  10. Improved hidden Markov models for molecular motors, part 2: extensions and application to experimental data.

    PubMed

    Syed, Sheyum; Müllner, Fiona E; Selvin, Paul R; Sigworth, Fred J

    2010-12-01

    Unbiased interpretation of noisy single molecular motor recordings remains a challenging task. To address this issue, we have developed robust algorithms based on hidden Markov models (HMMs) of motor proteins. The basic algorithm, called variable-stepsize HMM (VS-HMM), was introduced in the previous article. It improves on currently available Markov-model based techniques by allowing for arbitrary distributions of step sizes, and shows excellent convergence properties for the characterization of staircase motor timecourses in the presence of large measurement noise. In this article, we extend the VS-HMM framework for better performance with experimental data. The extended algorithm, variable-stepsize integrating-detector HMM (VSI-HMM) better models the data-acquisition process, and accounts for random baseline drifts. Further, as an extension, maximum a posteriori estimation is provided. When used as a blind step detector, the VSI-HMM outperforms conventional step detectors. The fidelity of the VSI-HMM is tested with simulations and is applied to in vitro myosin V data where a small 10 nm population of steps is identified. It is also applied to an in vivo recording of melanosome motion, where strong evidence is found for repeated, bidirectional steps smaller than 8 nm in size, implying that multiple motors simultaneously carry the cargo.

  11. Effectiveness of beads for tracking small-scale molecular motor dynamics

    NASA Astrophysics Data System (ADS)

    Lade, Steven J.; Craig, Erin M.; Linke, Heiner

    2011-08-01

    Investigations into molecular motor dynamics are increasingly focused on small-scale features of the motor’s motion. We define performance measures of a common type of single-molecule motility assay, the bead assay, for its ability to detect such features. Using numerical models, we explore the dependence of assay performance on a number of experimentally controllable parameters, including bead size, optical force, and the method of attaching the bead to the motor. We find that the best parameter choice depends on the objective of the experiments, and give a guide to parameter selection. Comparison of the models against experimental data from a recent bead assay of myosin V exemplifies how our methods can also be used to extract additional information from bead assays, particularly that related to small-scale features. By analyzing the experimental data we find evidence for previously undetected multiple waiting states of the bead-motor complex. Furthermore, from numerical simulations we find that equilibrium bead dynamics display features previously attributed to aborted motor steps, and that bead dynamics alone can produce multiple subphases during a step.

  12. Discrete Step Sizes of Molecular Motors Lead to Bimodal Non-Gaussian Velocity Distributions under Force.

    PubMed

    Vu, Huong T; Chakrabarti, Shaon; Hinczewski, Michael; Thirumalai, D

    2016-08-12

    Fluctuations in the physical properties of biological machines are inextricably linked to their functions. Distributions of run lengths and velocities of processive molecular motors, like kinesin-1, are accessible through single-molecule techniques, but rigorous theoretical models for these probabilities are lacking. Here, we derive exact analytic results for a kinetic model to predict the resistive force (F)-dependent velocity [P(v)] and run length [P(n)] distribution functions of generic finitely processive molecular motors. Our theory quantitatively explains the zero force kinesin-1 data for both P(n) and P(v) using the detachment rate as the only parameter. In addition, we predict the F dependence of these quantities. At nonzero F, P(v) is non-Gaussian and is bimodal with peaks at positive and negative values of v, which is due to the discrete step size of kinesin-1. Although the predictions are based on analyses of kinesin-1 data, our results are general and should hold for any processive motor, which walks on a track by taking discrete steps.

  13. Discrete Step Sizes of Molecular Motors Lead to Bimodal Non-Gaussian Velocity Distributions under Force

    NASA Astrophysics Data System (ADS)

    Vu, Huong T.; Chakrabarti, Shaon; Hinczewski, Michael; Thirumalai, D.

    2016-08-01

    Fluctuations in the physical properties of biological machines are inextricably linked to their functions. Distributions of run lengths and velocities of processive molecular motors, like kinesin-1, are accessible through single-molecule techniques, but rigorous theoretical models for these probabilities are lacking. Here, we derive exact analytic results for a kinetic model to predict the resistive force (F )-dependent velocity [P (v )] and run length [P (n )] distribution functions of generic finitely processive molecular motors. Our theory quantitatively explains the zero force kinesin-1 data for both P (n ) and P (v ) using the detachment rate as the only parameter. In addition, we predict the F dependence of these quantities. At nonzero F , P (v ) is non-Gaussian and is bimodal with peaks at positive and negative values of v , which is due to the discrete step size of kinesin-1. Although the predictions are based on analyses of kinesin-1 data, our results are general and should hold for any processive motor, which walks on a track by taking discrete steps.

  14. Mechanochemical coupling of the motion of molecular motors to ATP hydrolysis.

    PubMed Central

    Astumian, R D; Bier, M

    1996-01-01

    The typical biochemical paradigm for coupling between hydrolysis of ATP and the performance of chemical or mechanical work involves a well-defined sequence of events (a kinetic mechanism) with a fixed stoichiometry between the number of ATP molecules hydrolyzed and the turnover of the output reaction. Recent experiments show, however, that such a deterministic picture of coupling may not be adequate to explain observed behavior of molecular motor proteins in the presence of applied forces. Here we present a general model in which the binding of ATP and release of ADP serve to modulate the binding energy of a motor protein as it travels along a biopolymer backbone. The mechanism is loosely coupled--the average number of ATPs hydrolyzed to cause a single step from one binding site to the next depends strongly on the magnitude of an applied force and on the effective viscous drag force. The statistical mechanical perspective described here offers insight into how local anisotrophy along the "track" for a molecular motor, combined with an energy-releasing chemical reaction to provide a source of nonequilibrium fluctuations, can lead to macroscopic motion. Images Scheme 1 FIGURE 1 PMID:8789082

  15. Structure of the torque ring of the flagellar motor and the molecular basis for rotational switching

    SciTech Connect

    Lee, Lawrence K.; Ginsburg, Michael A.; Crovace, Claudia; Donohoe, Mhairi; Stock, Daniela

    2010-09-13

    The flagellar motor drives the rotation of flagellar filaments at hundreds of revolutions per second, efficiently propelling bacteria through viscous media. The motor uses the potential energy from an electrochemical gradient of cations across the cytoplasmic membrane to generate torque. A rapid switch from anticlockwise to clockwise rotation determines whether a bacterium runs smoothly forward or tumbles to change its trajectory. A protein called FliG forms a ring in the rotor of the flagellar motor that is involved in the generation of torque through an interaction with the cation-channel-forming stator subunit MotA. FliG has been suggested to adopt distinct conformations that induce switching but these structural changes and the molecular mechanism of switching are unknown. Here we report the molecular structure of the full-length FliG protein, identify conformational changes that are involved in rotational switching and uncover the structural basis for the formation of the FliG torque ring. This allows us to propose a model of the complete ring and switching mechanism in which conformational changes in FliG reverse the electrostatic charges involved in torque generation.

  16. A minimal system allowing tubulation with molecular motors pulling on giant liposomes

    PubMed Central

    Roux, Aurélien; Cappello, Giovanni; Cartaud, Jean; Prost, Jacques; Goud, Bruno; Bassereau, Patricia

    2002-01-01

    The elucidation of physical and molecular mechanisms by which a membrane tube is generated from a membrane reservoir is central to the understanding of the structure and dynamics of intracellular organelles and of transport intermediates in eukaryotic cells. Compelling evidence exists that molecular motors of the dynein and kinesin families are involved in the tubulation of organelles. Here, we show that lipid giant unilamellar vesicles (GUVs), to which kinesin molecules have been attached by means of small polystyrene beads, give rise to membrane tubes and to complex tubular networks when incubated in vitro with microtubules and ATP. Similar tubes and networks are obtained with GUVs made of purified Golgi lipids, as well as with Golgi membranes. No tube formation was observed when kinesins were directly bound to the GUV membrane, suggesting that it is critical to distribute the load on both lipids and motors by means of beads. A kinetic analysis shows that network growth occurs in two phases: a phase in which membrane-bound beads move at the same velocity than free beads, followed by a phase in which the tube growth rate decreases and strongly fluctuates. Our work demonstrates that the action of motors bound to a lipid bilayer is sufficient to generate membrane tubes and opens the way to well controlled experiments aimed at the understanding of basic mechanisms in intracellular transport. PMID:11959994

  17. A minimal system allowing tubulation with molecular motors pulling on giant liposomes

    NASA Astrophysics Data System (ADS)

    Roux, Aurélien; Cappello, Giovanni; Cartaud, Jean; Prost, Jacques; Goud, Bruno; Bassereau, Patricia

    2002-04-01

    The elucidation of physical and molecular mechanisms by which a membrane tube is generated from a membrane reservoir is central to the understanding of the structure and dynamics of intracellular organelles and of transport intermediates in eukaryotic cells. Compelling evidence exists that molecular motors of the dynein and kinesin families are involved in the tubulation of organelles. Here, we show that lipid giant unilamellar vesicles (GUVs), to which kinesin molecules have been attached by means of small polystyrene beads, give rise to membrane tubes and to complex tubular networks when incubated in vitro with microtubules and ATP. Similar tubes and networks are obtained with GUVs made of purified Golgi lipids, as well as with Golgi membranes. No tube formation was observed when kinesins were directly bound to the GUV membrane, suggesting that it is critical to distribute the load on both lipids and motors by means of beads. A kinetic analysis shows that network growth occurs in two phases: a phase in which membrane-bound beads move at the same velocity than free beads, followed by a phase in which the tube growth rate decreases and strongly fluctuates. Our work demonstrates that the action of motors bound to a lipid bilayer is sufficient to generate membrane tubes and opens the way to well controlled experiments aimed at the understanding of basic mechanisms in intracellular transport.

  18. Carbon Nanotube Based Molecular Electronics and Motors: A View from Classical and Quantum Dynamics Simulations

    NASA Technical Reports Server (NTRS)

    Srivastava, Deepak; Saini, Subhash (Technical Monitor)

    1998-01-01

    The tubular forms of fullerenes popularly known as carbon nanotubes are experimentally produced as single-, multiwall, and rope configurations. The nanotubes and nanoropes have shown to exhibit unusual mechanical and electronic properties. The single wall nanotubes exhibit both semiconducting and metallic behavior. In short undefected lengths they are the known strongest fibers which are unbreakable even when bent in half. Grown in ropes their tensile strength is approximately 100 times greater than steel at only one sixth the weight. Employing large scale classical and quantum molecular dynamics simulations we will explore the use of carbon nanotubes and carbon nanotube junctions in 2-, 3-, and 4-point molecular electronic device components, dynamic strength characterization for compressive, bending and torsional strains, and chemical functionalization for possible use in a nanoscale molecular motor. The above is an unclassified material produced for non-competitive basic research in the nanotechnology area.

  19. A metal switch for controlling the activity of molecular motor proteins.

    PubMed

    Cochran, Jared C; Zhao, Yu Cheng; Wilcox, Dean E; Kull, F Jon

    2011-12-25

    Kinesins are molecular motors that require a divalent metal ion (for example, Mg(2+)) to convert the energy of ATP hydrolysis into directed force production along microtubules. Here we present the crystal structure of a recombinant kinesin motor domain bound to Mn(2+) and ADP and report on a serine-to-cysteine substitution in the switch 1 motif of kinesin that allows its ATP hydrolysis activity to be controlled by adjusting the ratio of Mn(2+) to Mg(2+). This mutant kinesin binds ATP similarly in the presence of either metal ion, but its ATP hydrolysis activity is greatly diminished in the presence of Mg(2+). In human kinesin-1 and kinesin-5 as well as Drosophila melanogaster kinesin-10 and kinesin-14, this defect is rescued by Mn(2+), providing a way to control both the enzymatic activity and force-generating ability of these nanomachines.

  20. Discrete Kinetic Models for Molecular Motors: Asymptotic Velocity and Gaussian Fluctuations

    NASA Astrophysics Data System (ADS)

    Faggionato, Alessandra; Silvestri, Vittoria

    2014-12-01

    We consider random walks on quasi one dimensional lattices, as introduced in Faggionato and Silvestri (Random Walks on Quasi One Dimensional Lattices: Large Deviations and Fluctuation Theorems, 2014). This mathematical setting covers a large class of discrete kinetic models for non-cooperative molecular motors on periodic tracks. We derive general formulas for the asymptotic velocity and diffusion coefficient, and we show how to reduce their computation to suitable linear systems of the same degree of a single fundamental cell, with possible linear chain removals. We apply the above results to special families of kinetic models, also catching some errors in the biophysics literature.

  1. Molecular genetics of myosin motors in Arabidopsis. Final report, July 1, 1992--June 30, 1996

    SciTech Connect

    Schiefelbein, J.

    1997-02-01

    The normal growth and development of plant cells depends on the precise organization and distribution of the cellular contents. The basic goal of this investigation was to define a group of the molecules that are involved in organizing and transporting plant cell components. Based largely on studies of animal and fungal cells, one of the molecules thought to be involved in intracellular trafficking in plants is the actin-based motor protein myosin. Therefore, the major aim of this study was to isolate and analyze plant genes encoding myosin proteins. The plant of choice for these experiments was Arabidopsis thaliana, which offers numerous advantages for molecular genetics research.

  2. Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function.

    PubMed

    Otero, Maria G; Alloatti, Matías; Cromberg, Lucas E; Almenar-Queralt, Angels; Encalada, Sandra E; Pozo Devoto, Victorio M; Bruno, Luciana; Goldstein, Lawrence S B; Falzone, Tomás L

    2014-04-01

    Protein degradation by the ubiquitin-proteasome system in neurons depends on the correct delivery of the proteasome complex. In neurodegenerative diseases, aggregation and accumulation of proteins in axons link transport defects with degradation impairments; however, the transport properties of proteasomes remain unknown. Here, using in vivo experiments, we reveal the fast anterograde transport of assembled and functional 26S proteasome complexes. A high-resolution tracking system to follow fluorescent proteasomes revealed three types of motion: actively driven proteasome axonal transport, diffusive behavior in a viscoelastic axonema and proteasome-confined motion. We show that active proteasome transport depends on motor function because knockdown of the KIF5B motor subunit resulted in impairment of the anterograde proteasome flux and the density of segmental velocities. Finally, we reveal that neuronal proteasomes interact with intracellular membranes and identify the coordinated transport of fluorescent proteasomes with synaptic precursor vesicles, Golgi-derived vesicles, lysosomes and mitochondria. Taken together, our results reveal fast axonal transport as a new mechanism of proteasome delivery that depends on membrane cargo 'hitch-hiking' and the function of molecular motors. We further hypothesize that defects in proteasome transport could promote abnormal protein clearance in neurodegenerative diseases.

  3. Special Feature: Liquids and Structural Glasses Special Feature: An active biopolymer network controlled by molecular motors

    NASA Astrophysics Data System (ADS)

    Koenderink, Gijsje H.; Dogic, Zvonimir; Nakamura, Fumihiko; Bendix, Poul M.; MacKintosh, Frederick C.; Hartwig, John H.; Stossel, Thomas P.; Weitz, David A.

    2009-09-01

    We describe an active polymer network in which processive molecular motors control network elasticity. This system consists of actin filaments cross-linked by filamin A (FLNa) and contracted by bipolar filaments of muscle myosin II. The myosin motors stiffen the network by more than two orders of magnitude by pulling on actin filaments anchored in the network by FLNa cross-links, thereby generating internal stress. The stiffening response closely mimics the effects of external stress applied by mechanical shear. Both internal and external stresses can drive the network into a highly nonlinear, stiffened regime. The active stress reaches values that are equivalent to an external stress of 14 Pa, consistent with a 1-pN force per myosin head. This active network mimics many mechanical properties of cells and suggests that adherent cells exert mechanical control by operating in a nonlinear regime where cell stiffness is sensitive to changes in motor activity. This design principle may be applicable to engineering novel biologically inspired, active materials that adjust their own stiffness by internal catalytic control.

  4. A chemically powered unidirectional rotary molecular motor based on a palladium redox cycle

    NASA Astrophysics Data System (ADS)

    Collins, Beatrice S. L.; Kistemaker, Jos C. M.; Otten, Edwin; Feringa, Ben L.

    2016-09-01

    The conversion of chemical energy to drive directional motion at the molecular level allows biological systems, ranging from subcellular components to whole organisms, to perform a myriad of dynamic functions and respond to changes in the environment. Directional movement has been demonstrated in artificial molecular systems, but the fundamental motif of unidirectional rotary motion along a single-bond rotary axle induced by metal-catalysed transformation of chemical fuels has not been realized, and the challenge is to couple the metal-centred redox processes to stepwise changes in conformation to arrive at a full unidirectional rotary cycle. Here, we present the design of an organopalladium-based motor and the experimental demonstration of a 360° unidirectional rotary cycle using simple chemical fuels. Exploiting fundamental reactivity principles in organometallic chemistry enables control of directional rotation and offers the potential of harnessing the wealth of opportunities offered by transition-metal-based catalytic conversions to drive motion and dynamic functions.

  5. Totally asymmetric simple exclusion process simulations of molecular motor transport on random networks with asymmetric exit rates

    NASA Astrophysics Data System (ADS)

    Denisov, D. V.; Miedema, D. M.; Nienhuis, B.; Schall, P.

    2015-11-01

    Using the totally asymmetric simple-exclusion-process and mean-field transport theory, we investigate the transport in closed random networks with simple crossing topology—two incoming, two outgoing segments, as a model for molecular motor motion along biopolymer networks. Inspired by in vitro observation of molecular motor motion, we model the motor behavior at the intersections by introducing different exit rates for the two outgoing segments. Our simulations of this simple network reveal surprisingly rich behavior of the transport current with respect to the global density and exit rate ratio. For asymmetric exit rates, we find a broad current plateau at intermediate motor densities resulting from the competition of two subnetwork populations. This current plateau leads to stabilization of transport properties within such networks.

  6. Are two-station biased random walkers always potential molecular motors?

    PubMed

    Bakalis, Evangelos; Zerbetto, Francesco

    2015-01-12

    The short answer to the title question is no. Despite their tremendous complexity, many nanomachines are simply one-dimensional systems undergoing a biased, that is, unidirectional, walk on a two-minima potential energy curve. The initially prepared state, or station, is higher in energy than the final equilibrium state that is reached after overcoming an energy barrier. All chemical reactions comply with this scheme, which does not necessarily imply that a generic chemical reaction is a potential molecular motor. If the barrier is low, the system may walk back and the motion will have a large purely Brownian component. Alternatively, a large distance from the barrier of either of the two stations may introduce a Brownian component. Starting from a general inequality that leverages on the idea that the amount of heat dissipated along the potential energy curve is a good indication of the effectiveness of the biased walk, we provide guidelines for the selection of the features of artificial molecular motors.

  7. The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L

    PubMed Central

    Assis, L. H. P.; Silva-Junior, R. M. P.; Dolce, L. G.; Alborghetti, M. R.; Honorato, R. V.; Nascimento, A. F. Z.; Melo-Hanchuk, T. D.; Trindade, D. M.; Tonoli, C. C. C.; Santos, C. T.; Oliveira, P. S. L.; Larson, R. E.; Kobarg, J.; Espreafico, E. M.; Giuseppe, P. O.; Murakami, M. T.

    2017-01-01

    Myosin Va (MyoVa) is an actin-based molecular motor abundantly found at the centrosome. However, the role of MyoVa at this organelle has been elusive due to the lack of evidence on interacting partners or functional data. Herein, we combined yeast two-hybrid screen, biochemical studies and cellular assays to demonstrate that MyoVa interacts with RPGRIP1L, a cilia-centrosomal protein that controls ciliary signaling and positioning. MyoVa binds to the C2 domains of RPGRIP1L via residues located near or in the Rab11a-binding site, a conserved site in the globular tail domain (GTD) from class V myosins. According to proximity ligation assays, MyoVa and RPGRIP1L can interact near the cilium base in ciliated RPE cells. Furthermore, we showed that RPE cells expressing dominant-negative constructs of MyoVa are mostly unciliated, providing the first experimental evidence about a possible link between this molecular motor and cilia-related processes. PMID:28266547

  8. Adhesion of photon-driven molecular motors to surfaces via 1,3-dipolar cycloadditions: effect of interfacial interactions on molecular motion.

    PubMed

    Carroll, Gregory T; London, Gábor; Landaluce, Tatiana Fernández; Rudolf, Petra; Feringa, Ben L

    2011-01-25

    We report the attachment of altitudinal light-driven molecular motors to surfaces using 1,3-dipolar cycloaddition reactions. Molecular motors were designed containing azide or alkyne groups for attachment to alkyne- or azide-modified surfaces. Surface attachment was characterized by UV-vis, IR, XPS, and ellipsometry measurements. Surface-bound motors were found to undergo photochemical and thermal isomerizations consistent with unidirectional rotation in solution. Confinement at a surface was found to reduce the rate of the thermal isomerization process. The rate of thermal isomerization was also dependent on the surface coverage of the motors. In solution, changes in the UV-vis signal that accompany thermal isomerization can be fit with a single monoexponential decay. In contrast, thermal isomerization of the surface-bound motors does not follow a single monoexponential decay and was found to fit a biexponential decay. Both one- and two-legged motors were attached to surfaces. The kinetics of thermal isomerization was not affected by the valency of attachment, indicating that the changes in kinetics from solution to surface systems are related to interactions between the surface-bound motors.

  9. Synthetic Molecular Motors: Thermal N Inversion and Directional Photoinduced C=N Bond Rotation of Camphorquinone Imines.

    PubMed

    Greb, Lutz; Eichhöfer, Andreas; Lehn, Jean-Marie

    2015-11-23

    The thermal and photochemical E/Z isomerization of camphorquinone-derived imines was studied by a combination of kinetic, structural, and computational methods. The thermal isomerization proceeds by linear N inversion, whereas the photoinduced process occurs through C=N bond rotation with preferred directionality as a result of diastereoisomerism. Thereby, these imines are arguably the simplest example of synthetic molecular motors. The generality of the orthogonal trajectories of the thermal and photochemical pathways allows for the postulation that every suitable chiral imine qualifies, in principle, as a molecular motor driven by light or heat.

  10. Metastasis suppressor, NDRG1, mediates its activity through signaling pathways and molecular motors.

    PubMed

    Sun, Jing; Zhang, Daohai; Bae, Dong-Hun; Sahni, Sumit; Jansson, Patric; Zheng, Ying; Zhao, Qian; Yue, Fei; Zheng, Minhua; Kovacevic, Zaklina; Richardson, Des R

    2013-09-01

    The metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1), is negatively correlated with tumor progression in multiple neoplasms, being a promising new target for cancer treatment. However, the precise molecular effects of NDRG1 remain unclear. Herein, we summarize recent advances in understanding the impact of NDRG1 on cancer metastasis with emphasis on its interactions with the key oncogenic nuclear factor-kappaB, phosphatidylinositol-3 kinase/phosphorylated AKT/mammalian target of rapamycin and Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways. Recent studies demonstrating the inhibitory effects of NDRG1 on the epithelial-mesenchymal transition, a key initial step in metastasis, TGF-β pathway and the Wnt/β-catenin pathway are also described. Furthermore, NDRG1 was also demonstrated to regulate molecular motors in cancer cells, leading to inhibition of F-actin polymerization, stress fiber formation and subsequent reduction of cancer cell migration. Collectively, this review summarizes the underlying molecular mechanisms of the antimetastatic effects of NDRG1 in cancer cells.

  11. Elastic properties of dynein motor domain obtained from all-atom molecular dynamics simulations.

    PubMed

    Kamiya, Narutoshi; Mashimo, Tadaaki; Takano, Yu; Kon, Takahide; Kurisu, Genji; Nakamura, Haruki

    2016-08-01

    Dyneins are large microtubule motor proteins that convert ATP energy to mechanical power. High-resolution crystal structures of ADP-bound cytoplasmic dynein have revealed the organization of the motor domain, comprising the AAA(+) ring, the linker, the stalk/strut and the C sequence. Recently, the ADP.vanadate-bound structure, which is similar to the ATP hydrolysis transition state, revealed how the structure of dynein changes upon ATP binding. Although both the ADP- and ATP-bound state structures have been resolved, the dynamic properties at the atomic level remain unclear. In this work, we built two models named 'the ADP model' and 'the ATP model', where ADP and ATP are bound to AAA1 in the AAA(+) ring, respectively, to observe the initial procedure of the structural change from the unprimed to the primed state. We performed 200-ns molecular dynamics simulations for both models and compared their structures and dynamics. The motions of the stalk, consisting of a long coiled coil with a microtubule-binding domain, significantly differed between the two models. The elastic properties of the stalk were analyzed and compared with the experimental results.

  12. Reaction-diffusion-advection approach to spatially localized treadmilling aggregates of molecular motors

    NASA Astrophysics Data System (ADS)

    Yochelis, Arik; Bar-On, Tomer; Gov, Nir S.

    2016-04-01

    Unconventional myosins belong to a class of molecular motors that walk processively inside cellular protrusions towards the tips, on top of actin filament. Surprisingly, in addition, they also form retrograde moving self-organized aggregates. The qualitative properties of these aggregates are recapitulated by a mass conserving reaction-diffusion-advection model and admit two distinct families of modes: traveling waves and pulse trains. Unlike the traveling waves that are generated by a linear instability, pulses are nonlinear structures that propagate on top of linearly stable uniform backgrounds. Asymptotic analysis of isolated pulses via a simplified reaction-diffusion-advection variant on large periodic domains, allows to draw qualitative trends for pulse properties, such as the amplitude, width, and propagation speed. The results agree well with numerical integrations and are related to available empirical observations.

  13. A study of some non-equilibrium driven models and their contribution to the understanding of molecular motors

    NASA Astrophysics Data System (ADS)

    Mazilu, Irina; Gonzalez, Joshua

    2008-03-01

    From the point of view of a physicist, a bio-molecular motor represents an interesting non-equilibrium system and it is directly amenable to an analysis using standard methods of non-equilibrium statistical physics. We conduct a rigorous Monte Carlo study of three different driven lattice gas models that retain the basic behavior of three types of cytoskeletal molecular motors. Our models incorporate novel features such as realistic dynamics rules and complex motor-motor interactions. We are interested to have a deeper understanding of how various parameters influence the macroscopic behavior of these systems, what is the density profile and if the system undergoes a phase transition. On the analytical front, we computed the steady-state probability distributions exactly for the one of the models using the matrix method that was established in 1993 by B. Derrida et al. We also explored the possibilities offered by the ``Bethe ansatz'' method by mapping some well studied spin models into asymmetric simple exclusion models (already analyzed using computer simulations), and to use the results obtained for the spin models in finding an exact solution for our problem. We have exhaustive computational studies of the kinesin and dynein molecular motor models that prove to be very useful in checking our analytical work.

  14. Tug-of-war between two elastically coupled molecular motors: a case study on force generation and force balance.

    PubMed

    Uçar, Mehmet Can; Lipowsky, Reinhard

    2017-01-04

    Intracellular transport is performed by molecular motors that pull cargos along cytoskeletal filaments. Many cellular cargos are observed to move bidirectionally, with fast transport in both directions. This behaviour can be understood as a stochastic tug-of-war between two teams of antagonistic motors. The first theoretical model for such a tug-of-war, the Müller-Klumpp-Lipowsky (MKL) model, was based on two simplifying assumptions: (i) both motor teams move with the same velocity in the direction of the stronger team, and (ii) this velocity matching and the associated force balance arise immediately after the rebinding of an unbound motor to the filament. In this study, we extend the MKL model by including an elastic coupling between the antagonistic motors, and by allowing the motors to perform discrete motor steps. Each motor step changes the elastic interaction forces experienced by the motors. In order to elucidate the basic concepts of force balance and force fluctuations, we focus on the simplest case of two antagonistic motors, one kinesin against one dynein. We calculate the probability distribution for the spatial separation of the motors and the dependence of this distribution on the motors' unbinding rate. We also compute the probability distribution for the elastic interaction forces experienced by the motors, which determines the average elastic force 〈F〉 and the standard deviation of the force fluctuations around this average value. The average force 〈F〉 is found to decrease monotonically with increasing unbinding rate ε0. The behaviour of the MKL model is recovered in the limit of small ε0. In the opposite limit of large ε0, 〈F〉 is found to decay to zero as 1/ε0. Finally, we study the limiting case with ε0 = 0 for which we determine both the force statistics and the time needed to attain the steady state. Our theoretical predictions are accessible to experimental studies of in vitro systems consisting of two antagonistic motors

  15. The Utilization of Sensori-motor Experiences for Introducing Young Pupils to Molecular Motion: A Report of a Pilot Study.

    ERIC Educational Resources Information Center

    Hadzigeorgiou, Yannis

    2002-01-01

    Does a sensori-motor experience help a physics student understand the movement of molecules in solids, liquids, and gases? Students aged 9-10 were given either traditional demonstrations of solids, liquids, and gases and the variation of molecular motion with temperature (iconic presentation), or they were involved in physical activities as they…

  16. Specific Transformation of Assembly with Actin Filaments and Molecular Motors in a Cell-Sized Self-Emerged Liposome

    NASA Astrophysics Data System (ADS)

    Takiguchi, Kingo; Negishi, Makiko; Tanaka-Takiguchi, Yohko; Hayashi, Masahito; Yoshikawa, Kenichi

    2014-12-01

    Eukaryotes, by the same combination of cytoskeleton and molecular motor, for example actin filament and myosin, can generate a variety of movements. For this diversity, the organization of biological machineries caused by the confinement and/or crowding effects of internal living cells, may play very important roles.

  17. Adiabatic and non-adiabatic charge pumping in a single-level molecular motor

    NASA Astrophysics Data System (ADS)

    Napitu, B. D.; Thijssen, J. M.

    2015-07-01

    We propose a design for realizing quantum charge pump based on a recent proposal for a molecular motor (Seldenthuis J S et al 2010 ACS Nano 4 6681). Our design is based on the presence of a moiety with a permanent dipole moment which can rotate, thereby modulating the couplings to metallic contacts at both ends of the molecule. Using the non-equilibrium Keldysh Green’s function formalism (NEGF), we show that our design indeed generates a pump current. In the non-interacting pump, the variation of frequency from adiabatic to non-adiabatic regime, can be used to control the direction as well as the amplitude of the average current. The effect of Coulomb interaction is considered within the first- and the second- order perturbation. The numerical implementation of the scheme is quite demanding, and we develop an analytical approximation to obtain a speed-up giving results within a reasonable time. We find that the amplitude of the average pumped current can be controlled by both the driving frequency and the Coulomb interaction. The direction of of pumped current is shown to be determined by the phase difference between left and right anchoring groups.

  18. Parallel computation with molecular-motor-propelled agents in nanofabricated networks

    PubMed Central

    Nicolau, Dan V.; Lard, Mercy; Korten, Till; van Delft, Falco C. M. J. M.; Persson, Malin; Bengtsson, Elina; Månsson, Alf; Diez, Stefan; Linke, Heiner; Nicolau, Dan V.

    2016-01-01

    The combinatorial nature of many important mathematical problems, including nondeterministic-polynomial-time (NP)-complete problems, places a severe limitation on the problem size that can be solved with conventional, sequentially operating electronic computers. There have been significant efforts in conceiving parallel-computation approaches in the past, for example: DNA computation, quantum computation, and microfluidics-based computation. However, these approaches have not proven, so far, to be scalable and practical from a fabrication and operational perspective. Here, we report the foundations of an alternative parallel-computation system in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. Exploring the network in a parallel fashion using a large number of independent, molecular-motor-propelled agents then solves the mathematical problem. This approach uses orders of magnitude less energy than conventional computers, thus addressing issues related to power consumption and heat dissipation. We provide a proof-of-concept demonstration of such a device by solving, in a parallel fashion, the small instance {2, 5, 9} of the subset sum problem, which is a benchmark NP-complete problem. Finally, we discuss the technical advances necessary to make our system scalable with presently available technology. PMID:26903637

  19. A theoretical model of a molecular-motor-powered microfluidics pump

    NASA Astrophysics Data System (ADS)

    Bull, Joseph L.

    2003-11-01

    Flow induced by translating and rotating beads within a circular channel is investigated as a model of a novel molecular-motor-powered microfluidics pump. Micro flows are often generated by external pumps, rather than by devices that are integral to the microfluidics chip. We are currently developing a micro-scale pump that could be part of a biosensor, "lab on a chip" device, drug delivery system, or other bio-microfluidics device. The pump consists of a kinesin-coated bead moving along a microtubule track in a circular channel. The model is developed from the Stokes equation subject to wall and bead boundary conditions, and is solved using the boundary element method. It is shown that the pump can generate flows in the atto- to pico-l/s range, and that there is an optimal loading for a given pump geometry that results in maximum pump efficiency. Increasing the diameter of the bead relative to the channel width increases the flow generated at the expense of requiring a higher force to move the bead. It is found that bead rotation can increase or reduce the power required, depending on the direction of rotation, and that positioning the bead slightly off center can reduce the required power input. This work is funded by DARPA.

  20. Physics of transport and traffic phenomena in biology: from molecular motors and cells to organisms

    NASA Astrophysics Data System (ADS)

    Chowdhury, Debashish; Schadschneider, Andreas; Nishinari, Katsuhiro

    2005-12-01

    Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukaryotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Novel efforts have been made to utilize some uni-cellular organisms as “micro-transporters”. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In this review we critically examine the current status of our understanding, expose the limitations of the existing methods, mention open challenging questions and speculate on the possible future directions of research in this interdisciplinary area where physics meets not only chemistry and biology but also (nano-)technology.

  1. Adiabatic and non-adiabatic charge pumping in a single-level molecular motor.

    PubMed

    Napitu, B D; Thijssen, J M

    2015-07-15

    We propose a design for realizing quantum charge pump based on a recent proposal for a molecular motor (Seldenthuis J S et al 2010 ACS Nano 4 6681). Our design is based on the presence of a moiety with a permanent dipole moment which can rotate, thereby modulating the couplings to metallic contacts at both ends of the molecule. Using the non-equilibrium Keldysh Green's function formalism (NEGF), we show that our design indeed generates a pump current. In the non-interacting pump, the variation of frequency from adiabatic to non-adiabatic regime, can be used to control the direction as well as the amplitude of the average current. The effect of Coulomb interaction is considered within the first- and the second- order perturbation. The numerical implementation of the scheme is quite demanding, and we develop an analytical approximation to obtain a speed-up giving results within a reasonable time. We find that the amplitude of the average pumped current can be controlled by both the driving frequency and the Coulomb interaction. The direction of of pumped current is shown to be determined by the phase difference between left and right anchoring groups.

  2. Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

    PubMed

    Otero, Toribio F

    2017-01-18

    In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (Ea), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. Ea, k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

  3. Silanization of quartz, silicon and mica surfaces with light-driven molecular motors: construction of surface-bound photo-active nanolayers.

    PubMed

    London, Gábor; Carroll, Gregory T; Feringa, Ben L

    2013-06-07

    The attachment of molecular rotary motors containing triethoxysilane functional groups to quartz, silicon and mica surfaces is described. Motors containing silane coupling agents in their structure form stable molecular layers on quartz and silicon surfaces. Motors attached to these surfaces were found to undergo photochemical and thermal isomerization steps similar to those observed in solution. Additionally, successful formation of molecular "carpets" on atomically flat mica extending micrometer-sized length scales is presented. These "carpets" were found to undergo morphological changes upon irradiation with UV-light.

  4. Covalent Immobilization of Microtubules on Glass Surfaces for Molecular Motor Force Measurements and Other Single-Molecule Assays

    PubMed Central

    Nicholas, Matthew P.; Rao, Lu; Gennerich, Arne

    2014-01-01

    Rigid attachment of microtubules (MTs) to glass cover slip surfaces is a prerequisite for a variety of microscopy experiments in which MTs are used as substrates for MT-associated proteins, such as the molecular motors kinesin and cytoplasmic dynein. We present an MT-surface coupling protocol in which aminosilanized glass is formylated using the cross-linker glutaraldehyde, fluorescence-labeled MTs are covalently attached, and the surface is passivated with highly pure beta-casein. The technique presented here yields rigid MT immobilization while simultaneously blocking the remaining glass surface against nonspecific binding by polystyrene optical trapping microspheres. This surface chemistry is straightforward and relatively cheap and uses a minimum of specialized equipment or hazardous reagents. These methods provide a foundation for a variety of optical tweezers experiments with MT-associated molecular motors and may also be useful in other assays requiring surface-immobilized proteins. PMID:24633798

  5. Interrogating Emergent Transport Properties for Molecular Motor Ensembles: A Semi-analytical Approach

    PubMed Central

    Materassi, Donatello; Li, Mingang; Hays, Thomas; Salapaka, Murti

    2016-01-01

    Intracellular transport is an essential function in eucaryotic cells, facilitated by motor proteins—proteins converting chemical energy into kinetic energy. It is understood that motor proteins work in teams enabling unidirectional and bidirectional transport of intracellular cargo over long distances. Disruptions of the underlying transport mechanisms, often caused by mutations that alter single motor characteristics, are known to cause neurodegenerative diseases. For example, phosphorylation of kinesin motor domain at the serine residue is implicated in Huntington’s disease, with a recent study of phosphorylated and phosphomimetic serine residues indicating lowered single motor stalling forces. In this article we report the effects of mutations of this nature on transport properties of cargo carried by multiple wild-type and mutant motors. Results indicate that mutants with altered stall forces might determine the average velocity and run-length even when they are outnumbered by wild type motors in the ensemble. It is shown that mutants gain a competitive advantage and lead to an increase in the expected run-length when the load on the cargo is in the vicinity of the mutant’s stalling force or a multiple of its stalling force. A separate contribution of this article is the development of a semi-analytic method to analyze transport of cargo by multiple motors of multiple types. The technique determines transition rates between various relative configurations of motors carrying the cargo using the transition rates between various absolute configurations. This enables a computation of biologically relevant quantities like average velocity and run-length without resorting to Monte Carlo simulations. It can also be used to introduce alterations of various single motor parameters to model a mutation and to deduce effects of such alterations on the transport of a common cargo by multiple motors. Our method is easily implementable and we provide a software package

  6. Molecular dynamics simulations and cross-link analysis of the rotary molecular motor F(o) of ATP synthase

    NASA Astrophysics Data System (ADS)

    Kanchanawarin, Chalermpol

    The protein F1Fo ATP synthase is responsible for the generation of the molecule adenosine tri-phosphate (ATP). It consists of two coupled rotary motors, F1 and Fo. ATP is generated via a rotary mechanism that couples the synthesis of ATP in F1 to the proton translocation across Fo which is driven by the electrochemical proton gradient across the membrane. F1 consists of three different subunits in the stoichiometry a1b2c10. So far, only the structure of the c-subunit and a partial structure of the b-subunit have been solved at atomic level detail. However, enough biochemical and structural information is available to construct an atomic model of Fo. There are still many open questions about Fo operation ranging from the subunit arrangement to the proton pathway and proton conduction mechanism to the rotary mechanism that couples the proton conduction to the rotation of its rotor. In this thesis study, I investigated the following four aspects of Fo: the proton pathway in Fo; the motion of F o subunits during its rotation; the rotation of the C-terminal helix of the c-subunit induced by a pH change; the forced rotation of a c10 ring in a membrane. Using molecular dynamics (MD) simulations, I was able to identify a proton pathway formed as two half proton channels in F o, i.e., a proton entrance channel and a proton exit channel. This is in good agreement with experiment. Furthermore, based on the diagramatic cross-link analysis, I propose a new Fo rotary mechanism which shows the cooperative movement of helices in Fo during proton transport and can explain experimental results which could not be explained by previous models. The investigation of the C-terminal helix rotation by NM simulations showed no pH induced rotation of the helix of the c-subunit. Finally, using steered MD simulations, I found that the c10 ring is mechanically robust against forced rotation in vacuum but not in a membrane on the MD time scale. Overall, structural information combined with my

  7. The nonlinear chemo-mechanic coupled dynamics of the F 1 -ATPase molecular motor.

    PubMed

    Xu, Lizhong; Liu, Fang

    2012-03-01

    The ATP synthase consists of two opposing rotary motors, F0 and F1, coupled to each other. When the F1 motor is not coupled to the F0 motor, it can work in the direction hydrolyzing ATP, as a nanomotor called F1-ATPase. It has been reported that the stiffness of the protein varies nonlinearly with increasing load. The nonlinearity has an important effect on the rotating rate of the F1-ATPase. Here, considering the nonlinearity of the γ shaft stiffness for the F1-ATPase, a nonlinear chemo-mechanical coupled dynamic model of F1 motor is proposed. Nonlinear vibration frequencies of the γ shaft and their changes along with the system parameters are investigated. The nonlinear stochastic response of the elastic γ shaft to thermal excitation is analyzed. The results show that the stiffness nonlinearity of the γ shaft causes an increase of the vibration frequency for the F1 motor, which increases the motor's rotation rate. When the concentration of ATP is relatively high and the load torque is small, the effects of the stiffness nonlinearity on the rotating rates of the F1 motor are obvious and should be considered. These results are useful for improving calculation of the rotating rate for the F1 motor and provide insight about the stochastic wave mechanics of F1-ATPase.

  8. Kinetic modeling of molecular motors: pause model and parameter determination from single-molecule experiments

    NASA Astrophysics Data System (ADS)

    Morin, José A.; Ibarra, Borja; Cao, Francisco J.

    2016-05-01

    Single-molecule manipulation experiments of molecular motors provide essential information about the rate and conformational changes of the steps of the reaction located along the manipulation coordinate. This information is not always sufficient to define a particular kinetic cycle. Recent single-molecule experiments with optical tweezers showed that the DNA unwinding activity of a Phi29 DNA polymerase mutant presents a complex pause behavior, which includes short and long pauses. Here we show that different kinetic models, considering different connections between the active and the pause states, can explain the experimental pause behavior. Both the two independent pause model and the two connected pause model are able to describe the pause behavior of a mutated Phi29 DNA polymerase observed in an optical tweezers single-molecule experiment. For the two independent pause model all parameters are fixed by the observed data, while for the more general two connected pause model there is a range of values of the parameters compatible with the observed data (which can be expressed in terms of two of the rates and their force dependencies). This general model includes models with indirect entry and exit to the long-pause state, and also models with cycling in both directions. Additionally, assuming that detailed balance is verified, which forbids cycling, this reduces the ranges of the values of the parameters (which can then be expressed in terms of one rate and its force dependency). The resulting model interpolates between the independent pause model and the indirect entry and exit to the long-pause state model

  9. Selective cell-surface labeling of the molecular motor protein prestin

    SciTech Connect

    McGuire, Ryan M.; Silberg, Jonathan J.; Pereira, Fred A.; Raphael, Robert M.

    2011-06-24

    Highlights: {yields} Trafficking to the plasma membrane is required for prestin function. {yields} Biotin acceptor peptide (BAP) was fused to prestin through a transmembrane domain. {yields} BAP-prestin can be metabolically labeled with biotin in HEK293 cells. {yields} Biotin-BAP-prestin allows for selective imaging of fully trafficked prestin. {yields} The biotin-BAP-prestin displays voltage-sensitive activity. -- Abstract: Prestin, a multipass transmembrane protein whose N- and C-termini are localized to the cytoplasm, must be trafficked to the plasma membrane to fulfill its cellular function as a molecular motor. One challenge in studying prestin sequence-function relationships within living cells is separating the effects of amino acid substitutions on prestin trafficking, plasma membrane localization and function. To develop an approach for directly assessing prestin levels at the plasma membrane, we have investigated whether fusion of prestin to a single pass transmembrane protein results in a functional fusion protein with a surface-exposed N-terminal tag that can be detected in living cells. We find that fusion of the biotin-acceptor peptide (BAP) and transmembrane domain of the platelet-derived growth factor receptor (PDGFR) to the N-terminus of prestin-GFP yields a membrane protein that can be metabolically-labeled with biotin, trafficked to the plasma membrane, and selectively detected at the plasma membrane using fluorescently-tagged streptavidin. Furthermore, we show that the addition of a surface detectable tag and a single-pass transmembrane domain to prestin does not disrupt its voltage-sensitive activity.

  10. The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET.

    PubMed

    Ho, James; Sielaff, Hendrik; Nadeem, Aftab; Svanborg, Catharina; Grüber, Gerhard

    2015-05-22

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) interacts with multiple tumor cell compartments, affecting cell morphology, metabolism, proteasome function, chromatin structure and viability. This study investigated if these diverse effects of HAMLET might be caused, in part, by a direct effect on the ATP synthase and a resulting reduction in cellular ATP levels. A dose-dependent reduction in cellular ATP levels was detected in A549 lung carcinoma cells, and by confocal microscopy, co-localization of HAMLET with the nucleotide-binding subunits α (non-catalytic) and β (catalytic) of the energy converting F1F0 ATP synthase was detected. As shown by fluorescence correlation spectroscopy, HAMLET binds to the F1 domain of the F1F0 ATP synthase with a dissociation constant (KD) of 20.5μM. Increasing concentrations of the tumoricidal protein HAMLET added to the enzymatically active α3β3γ complex of the F-ATP synthase lowered its ATPase activity, demonstrating that HAMLET binding to the F-ATP synthase effects the catalysis of this molecular motor. Single-molecule analysis was applied to study HAMLET-α3β3γ complex interaction. Whereas the α3β3γ complex of the F-ATP synthase rotated in a counterclockwise direction with a mean rotational rate of 3.8±0.7s(-1), no rotation could be observed in the presence of bound HAMLET. Our findings suggest that direct effects of HAMLET on the F-ATP synthase may inhibit ATP-dependent cellular processes.

  11. Prokaryotic and eukaryotic DNA helicases. Essential molecular motor proteins for cellular machinery.

    PubMed

    Tuteja, Narendra; Tuteja, Renu

    2004-05-01

    DNA helicases are ubiquitous molecular motor proteins which harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of energetically stable duplex DNA, and thus play important roles in nearly all aspects of nucleic acid metabolism, including replication, repair, recombination, and transcription. They break the hydrogen bonds between the duplex helix and move unidirectionally along the bound strand. All helicases are also translocases and DNA-dependent ATPases. Most contain conserved helicase motifs that act as an engine to power DNA unwinding. All DNA helicases share some common properties, including nucleic acid binding, NTP binding and hydrolysis, and unwinding of duplex DNA in the 3' to 5' or 5' to 3' direction. The minichromosome maintenance (Mcm) protein complex (Mcm4/6/7) provides a DNA-unwinding function at the origin of replication in all eukaryotes and may act as a licensing factor for DNA replication. The RecQ family of helicases is highly conserved from bacteria to humans and is required for the maintenance of genome integrity. They have also been implicated in a variety of human genetic disorders. Since the discovery of the first DNA helicase in Escherichia coli in 1976, and the first eukaryotic one in the lily in 1978, a large number of these enzymes have been isolated from both prokaryotic and eukaryotic systems, and the number is still growing. In this review we cover the historical background of DNA helicases, helicase assays, biochemical properties, prokaryotic and eukaryotic DNA helicases including Mcm proteins and the RecQ family of helicases. The properties of most of the known DNA helicases from prokaryotic and eukaryotic systems, including viruses and bacteriophages, are summarized in tables.

  12. A simple statistical approach to the boyer model of the molecular motor adenosine triphosphatase

    SciTech Connect

    Loginov, E. B. Pikin, S. A.

    2006-03-15

    A physical description of the F{sub 0}F{sub 1} adenosine triphosphatase as a rotating motor is proposed. The catalytic center and the ion-conducting membrane are considered within the classical Boyer model for the rotor and the catalytic parts of the motor, thereby allowing application of a simple three-pole model, which decreases the number of parameters significantly. The stochastic character of the processes occurring in motors is described by the Fokker-Planck equations. Various dependences of the rotation speed on the degree of excitation, localization of excitations, and the amplitude of the potential are reported.

  13. Mechanical operation and intersubunit coordination of ring-shaped molecular motors: insights from single-molecule studies.

    PubMed

    Liu, Shixin; Chistol, Gheorghe; Bustamante, Carlos

    2014-05-06

    Ring NTPases represent a large and diverse group of proteins that couple their nucleotide hydrolysis activity to a mechanical task involving force generation and some type of transport process in the cell. Because of their shape, these enzymes often operate as gates that separate distinct cellular compartments to control and regulate the passage of chemical species across them. In this manner, ions and small molecules are moved across membranes, biopolymer substrates are segregated between cells or moved into confined spaces, double-stranded nucleic acids are separated into single strands to provide access to the genetic information, and polypeptides are unfolded and processed for recycling. Here we review the recent advances in the characterization of these motors using single-molecule manipulation and detection approaches. We describe the various mechanisms by which ring motors convert chemical energy to mechanical force or torque and coordinate the activities of individual subunits that constitute the ring. We also examine how single-molecule studies have contributed to a better understanding of the structural elements involved in motor-substrate interaction, mechanochemical coupling, and intersubunit coordination. Finally, we discuss how these molecular motors tailor their operation-often through regulation by other cofactors-to suit their unique biological functions.

  14. Computational design of faster rotating second-generation light-driven molecular motors by control of steric effects.

    PubMed

    Oruganti, Baswanth; Fang, Changfeng; Durbeej, Bo

    2015-09-07

    We report a systematic computational investigation of the possibility to accelerate the rate-limiting thermal isomerizations of the rotary cycles of synthetic light-driven overcrowded alkene-based molecular motors through modulation of steric interactions. Choosing as a reference system a second-generation motor known to accomplish rotary motion in the MHz regime and using density functional theory methods, we propose a three-step mechanism for the thermal isomerizations of this motor and show that variation of the steric bulkiness of the substituent at the stereocenter can reduce the (already small) free-energy barrier of the rate-determining step by a further 15-17 kJ mol(-1). This finding holds promise for future motors of this kind to reach beyond the MHz regime. Furthermore, we demonstrate and explain why one particular step is kinetically favored by decreasing and another step is kinetically favored by increasing the steric bulkiness of this substituent, and identify a possible back reaction capable of impeding the rotary rate.

  15. Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?

    PubMed Central

    Kumpula, Esa-Pekka; Kursula, Inari

    2015-01-01

    Apicomplexan parasites are the causative agents of notorious human and animal diseases that give rise to considerable human suffering and economic losses worldwide. The most prominent parasites of this phylum are the malaria-causing Plasmodium species, which are widespread in tropical and subtropical regions, and Toxoplasma gondii, which infects one third of the world’s population. These parasites share a common form of gliding motility which relies on an actin–myosin motor. The components of this motor and the actin-regulatory proteins in Apicomplexa have unique features compared with all other eukaryotes. This, together with the crucial roles of these proteins, makes them attractive targets for structure-based drug design. In recent years, several structures of glideosome components, in particular of actins and actin regulators from apicomplexan parasites, have been determined, which will hopefully soon allow the creation of a complete molecular picture of the parasite actin–myosin motor and its regulatory machinery. Here, current knowledge of the function of this motor is reviewed from a structural perspective. PMID:25945702

  16. Mechanical Operation and Intersubunit Coordination of Ring-Shaped Molecular Motors: Insights from Single-Molecule Studies

    PubMed Central

    Liu, Shixin; Chistol, Gheorghe; Bustamante, Carlos

    2014-01-01

    Ring NTPases represent a large and diverse group of proteins that couple their nucleotide hydrolysis activity to a mechanical task involving force generation and some type of transport process in the cell. Because of their shape, these enzymes often operate as gates that separate distinct cellular compartments to control and regulate the passage of chemical species across them. In this manner, ions and small molecules are moved across membranes, biopolymer substrates are segregated between cells or moved into confined spaces, double-stranded nucleic acids are separated into single strands to provide access to the genetic information, and polypeptides are unfolded and processed for recycling. Here we review the recent advances in the characterization of these motors using single-molecule manipulation and detection approaches. We describe the various mechanisms by which ring motors convert chemical energy to mechanical force or torque and coordinate the activities of individual subunits that constitute the ring. We also examine how single-molecule studies have contributed to a better understanding of the structural elements involved in motor-substrate interaction, mechanochemical coupling, and intersubunit coordination. Finally, we discuss how these molecular motors tailor their operation—often through regulation by other cofactors—to suit their unique biological functions. PMID:24806916

  17. Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?

    SciTech Connect

    Kumpula, Esa-Pekka; Kursula, Inari

    2015-04-16

    In this review, current structural understanding of the apicomplexan glideosome and actin regulation is described. Apicomplexan parasites are the causative agents of notorious human and animal diseases that give rise to considerable human suffering and economic losses worldwide. The most prominent parasites of this phylum are the malaria-causing Plasmodium species, which are widespread in tropical and subtropical regions, and Toxoplasma gondii, which infects one third of the world’s population. These parasites share a common form of gliding motility which relies on an actin–myosin motor. The components of this motor and the actin-regulatory proteins in Apicomplexa have unique features compared with all other eukaryotes. This, together with the crucial roles of these proteins, makes them attractive targets for structure-based drug design. In recent years, several structures of glideosome components, in particular of actins and actin regulators from apicomplexan parasites, have been determined, which will hopefully soon allow the creation of a complete molecular picture of the parasite actin–myosin motor and its regulatory machinery. Here, current knowledge of the function of this motor is reviewed from a structural perspective.

  18. A rotary molecular motor that can work at near 100% efficiency.

    PubMed Central

    Kinosita, K; Yasuda, R; Noji, H; Adachi, K

    2000-01-01

    A single molecule of F1-ATPase is by itself a rotary motor in which a central gamma-subunit rotates against a surrounding cylinder made of alpha3beta3-subunits. Driven by the three betas that sequentially hydrolyse ATP, the motor rotates in discrete 120 degree steps, as demonstrated in video images of the movement of an actin filament bound, as a marker, to the central gamma-subunit. Over a broad range of load (hydrodynamic friction against the rotating actin filament) and speed, the F1 motor produces a constant torque of ca. 40 pN nm. The work done in a 120 degree step, or the work per ATP molecule, is thus ca. 80 pN nm. In cells, the free energy of ATP hydrolysis is ca. 90 pN nm per ATP molecule, suggesting that the F1 motor can work at near 100% efficiency. We confirmed in vitro that F1 indeed does ca. 80 pN nm of work under the condition where the free energy per ATP is 90 pN nm. The high efficiency may be related to the fully reversible nature of the F1 motor: the ATP synthase, of which F1 is a part, is considered to synthesize ATP from ADP and phosphate by reverse rotation of the F1 motor. Possible mechanisms of F1 rotation are discussed. PMID:10836501

  19. Distal hereditary motor neuropathy with vocal cord paresis: from difficulty in choral singing to a molecular genetic diagnosis.

    PubMed

    Ingram, Gillian; Barwick, Katy E S; Hartley, Louise; McEntagart, Meriel; Crosby, Andrew H; Llewelyn, Gareth; Morris, Huw R

    2016-06-01

    Patients presenting with distal weakness can be a diagnostic challenge; the eventual diagnosis often depends upon accurate clinical phenotyping. We present a mother and daughter with a rare form of distal hereditary motor neuropathy type 7 in whom the diagnosis became apparent by initial difficulty in singing, from early vocal cord dysfunction. This rare neuropathy has now been identified in two apparently unrelated families in Wales. This family's clinical presentation is typical of distal hereditary motor neuropathy type 7, and they have the common truncating mutation in the SLC5A7 gene. Advances in genetic analysis of these rare conditions broaden our understanding of their potential molecular mechanisms and may allow more directed therapy.

  20. On the possibility to accelerate the thermal isomerizations of overcrowded alkene-based rotary molecular motors with electron-donating or electron-withdrawing substituents.

    PubMed

    Oruganti, Baswanth; Durbeej, Bo

    2016-09-01

    We employ computational methods to investigate the possibility of using electron-donating or electron-withdrawing substituents to reduce the free-energy barriers of the thermal isomerizations that limit the rotational frequencies achievable by synthetic overcrowded alkene-based molecular motors. Choosing as reference systems one of the fastest motors known to date and two variants thereof, we consider six new motors obtained by introducing electron-donating methoxy and dimethylamino or electron-withdrawing nitro and cyano substituents in conjugation with the central olefinic bond connecting the two (stator and rotator) motor halves. Performing density functional theory calculations, we then show that electron-donating (but not electron-withdrawing) groups at the stator are able to reduce the already small barriers of the reference motors by up to 18 kJ mol(-1). This result outlines a possible strategy for improving the rotational frequencies of motors of this kind. Furthermore, exploring the origin of the catalytic effect, it is found that electron-donating groups exert a favorable steric influence on the thermal isomerizations, which is not manifested by electron-withdrawing groups. This finding suggests a new mechanism for controlling the critical steric interactions of these motors. Graphical Abstract The introduction of electron-donating groups in one of the fastest rotary molecular motors known to date is found to reduce the free-energy barriers of the thermal steps that limit the rotational frequencies by up to 18 kJ mol(-1).

  1. An exact approach for studying cargo transport by an ensemble of molecular motors

    PubMed Central

    2013-01-01

    Background Intracellular transport is crucial for many cellular processes where a large fraction of the cargo is transferred by motor-proteins over a network of microtubules. Malfunctions in the transport mechanism underlie a number of medical maladies. Existing methods for studying how motor-proteins coordinate the transfer of a shared cargo over a microtubule are either analytical or are based on Monte-Carlo simulations. Approaches that yield analytical results, while providing unique insights into transport mechanism, make simplifying assumptions, where a detailed characterization of important transport modalities is difficult to reach. On the other hand, Monte-Carlo based simulations can incorporate detailed characteristics of the transport mechanism; however, the quality of the results depend on the number and quality of simulation runs used in arriving at results. Here, for example, it is difficult to simulate and study rare-events that can trigger abnormalities in transport. Results In this article, a semi-analytical methodology that determines the probability distribution function of motor-protein behavior in an exact manner is developed. The method utilizes a finite-dimensional projection of the underlying infinite-dimensional Markov model, which retains the Markov property, and enables the detailed and exact determination of motor configurations, from which meaningful inferences on transport characteristics of the original model can be derived. Conclusions Under this novel probabilistic approach new insights about the mechanisms of action of these proteins are found, suggesting hypothesis about their behavior and driving the design and realization of new experiments. The advantages provided in accuracy and efficiency make it possible to detect rare events in the motor protein dynamics, that could otherwise pass undetected using standard simulation methods. In this respect, the model has allowed to provide a possible explanation for possible mechanisms

  2. Identification of molecular motors in the Woods Hole squid, Loligo pealei: an expressed sequence tag approach.

    PubMed

    DeGiorgis, Joseph A; Cavaliere, Kimberly R; Burbach, J Peter H

    2011-10-01

    The squid giant axon and synapse are unique systems for studying neuronal function. While a few nucleotide and amino acid sequences have been obtained from squid, large scale genetic and proteomic information is lacking. We have been particularly interested in motors present in axons and their roles in transport processes. Here, to obtain genetic data and to identify motors expressed in squid, we initiated an expressed sequence tag project by single-pass sequencing mRNAs isolated from the stellate ganglia of the Woods Hole Squid, Loligo pealei. A total of 22,689 high quality expressed sequence tag (EST) sequences were obtained and subjected to basic local alignment search tool analysis. Seventy six percent of these sequences matched genes in the National Center for Bioinformatics databases. By CAP3 analysis this library contained 2459 contigs and 7568 singletons. Mining for motors successfully identified six kinesins, six myosins, a single dynein heavy chain, as well as components of the dynactin complex, and motor light chains and accessory proteins. This initiative demonstrates that EST projects represent an effective approach to obtain sequences of interest.

  3. Torque, chemistry and efficiency in molecular motors: a study of the rotary-chemical coupling in F1-ATPase.

    PubMed

    Mukherjee, Shayantani; Bora, Ram Prasad; Warshel, Arieh

    2015-11-01

    Detailed understanding of the action of biological molecular machines must overcome the challenge of gaining a clear knowledge of the corresponding free-energy landscape. An example for this is the elucidation of the nature of converting chemical energy to torque and work in the rotary molecular motor of F1-ATPase. A major part of the challenge involves understanding the rotary-chemical coupling from a non-phenomenological structure/energy description. Here we focused on using a coarse-grained model of F1-ATPase to generate a structure-based free-energy landscape of the rotary-chemical process of the whole system. In particular, we concentrated on exploring the possible impact of the position of the catalytic dwell on the efficiency and torque generation of the molecular machine. It was found that the experimentally observed torque can be reproduced with landscapes that have different positions for the catalytic dwell on the rotary-chemical surface. Thus, although the catalysis is undeniably required for torque generation, the experimentally observed position of the catalytic dwell at 80° might not have a clear advantage for the force generation by F1-ATPase. This further implies that the rotary-chemical couplings in these biological motors are quite robust and their efficiencies do not depend explicitly on the position of the catalytic dwells. Rather, the specific positioning of the dwells with respect to the rotational angle is a characteristic arising due to the structural construct of the molecular machine and might not bear any clear connection to the thermodynamic efficiency for the system.

  4. Testing a structural model for viral DNA packaging motor function by optical tweezers measurements, site directed mutagenesis, and molecular dynamics calculations

    NASA Astrophysics Data System (ADS)

    Keller, Nicholas A.; Migliori, Amy D.; Arya, Gaurav; Rao, Venigalla B.; Smith, Douglas E.

    2013-09-01

    Many double-stranded DNA viruses employ a molecular motor to package DNA into preformed capsid shells. Based on structures of phage T4 motor proteins determined by X-ray crystallography and cryo-electron microscopy, Rao, Rossmann and coworkers recently proposed a structural model for motor function. They proposed that DNA is ratcheted by a large conformational change driven by electrostatic interactions between charged residues at an interface between two globular domains of the motor protein. We have conducted experiments to test this model by studying the effect on packaging under applied load of site-directed changes altering these residues. We observe significant impairment of packaging activity including reductions in packaging rate, percent time packaging, and time active under high load. We show that these measured impairments correlate well with alterations in free energies associated with the conformational change predicted by molecular dynamics simulations.

  5. Coupling mechanical forces to electrical signaling: molecular motors and the intracellular transport of ion channels.

    PubMed

    Barry, Joshua; Gu, Chen

    2013-04-01

    Proper localization of various ion channels is fundamental to neuronal functions, including postsynaptic potential plasticity, dendritic integration, action potential initiation and propagation, and neurotransmitter release. Microtubule-based forward transport mediated by kinesin motors plays a key role in placing ion channel proteins to correct subcellular compartments. PDZ- and coiled-coil-domain proteins function as adaptor proteins linking ionotropic glutamate and GABA receptors to various kinesin motors, respectively. Recent studies show that several voltage-gated ion channel/transporter proteins directly bind to kinesins during forward transport. Three major regulatory mechanisms underlying intracellular transport of ion channels are also revealed. These studies contribute to understanding how mechanical forces are coupled to electrical signaling and illuminating pathogenic mechanisms in neurodegenerative diseases.

  6. Solution structure of two molecular motor domains: nonclaret disjunctional and kinesin.

    PubMed Central

    Eden, D; Luu, B Q; Zapata, D J; Sablin, E P; Kull, F J

    1995-01-01

    The effects of selected ligands on the structure of the truncated heavy-chain chemomechanical motor domains of Drosophila ncd and human kinesin were compared using the technique of transient electric birefringence. The 366-amino acid C-terminal motor domain of Drosophila nonclaret disjunctional, ncd(335-700), and the 349-amino acid N-terminal motor domain of human kinesin, kinesin(349), were studied at 4 degrees C in neutral buffers with ionic strength of 100 mM to form complexes with either MgADP or MgADP.Vi. The rotational diffusion time adjusted to 20 degrees C and water, tau 20,W, for ncd(335-700).MgADP is 32.8 ns, and for ncd(335-700).MgADP.Vi is 34.8 ns, suggesting prolate ellipsoids with dimensions 9.40 x 3.77 nm and 9.73 x 3.70 nm, respectively. The specific Kerr constant, Ksp, of ncd is -1.65 x 10(-12) cm2V-2 for the MgADP complex and -1.15 x 10(-12) cm2V-2 for the MgADP.Vi complex. The large negative Ksp for a prolate protein suggests an unusual charge distribution with two long surfaces with opposite charge. The tau 20,W for kinesin(349).MgADP is longer than the corresponding ncd motor and shows a decrease with increased electric field. The kinesin(349).MgADP.Vi complex has a longer tau 20,W. The Ksp for kinesin(349) is 0.36 x 10(-12) cm2V-2 for each complex. PMID:7787102

  7. The Molecular Basis of Cardiac Mechanics: Regulation of Motor Unit Recruitment

    DTIC Science & Technology

    2007-11-02

    bridges determines the affinity of the regulatory proteins for calcium. The force response to sarcomere length oscillations was measured at...strain gauge. Sarcomere oscillations were imposed with a fast servomotor. The force response lagged the sarcomere length oscillations at frequency...mm2) since each cubic millimeter of the cardiac or skeletal muscle contains 100•1012 motor units (The length of half sarcomere is around 1.0µm

  8. Local cytoskeletal and organelle interactions impact molecular motor-driven early endosomal trafficking

    PubMed Central

    Zajac, Allison L.; Goldman, Yale E.; Holzbaur, Erika L.F.; Ostap, E. Michael

    2013-01-01

    SUMMARY Background In the intracellular environment, motor-driven cargo must navigate a dense cytoskeletal network among abundant organelles. Results We investigated the effects of the crowded intracellular environment on early endosomal trafficking. Live-cell imaging of an endosomal cargo (endocytosed epidermal growth factor-conjugated quantum dots) combined with high-resolution tracking was used to analyze the heterogeneous motion of individual endosomes. The motile population of endosomes moved towards the perinuclear region in directed bursts of microtubule-based, dynein-dependent transport interrupted by longer periods of diffusive motion. Actin network density did not affect motile endosomes during directed runs or diffusive interruptions. Simultaneous two-color imaging was used to correlate changes in endosomal movement with potential obstacles to directed runs. Termination of directed runs spatially correlated with microtubule-dense regions, encounters with other endosomes, and interactions with the endoplasmic reticulum. During a subset of run terminations, we also observed merging and splitting of endosomes, deformation of the endoplasmic reticulum, and directional reversals at speeds up to ten-fold greater than characteristic in vitro motor velocities. These observations suggest endosomal membrane tension is high during directed run termination. Conclusions Our results indicate that the crowded cellular environment significantly impacts the motor-driven motility of organelles. Rather than simply acting as impediments to movement, interactions of trafficking cargos with intracellular obstacles may facilitate communication between membrane-bound compartments or contribute to the generation of membrane tension necessary for fusion and fission of endosomal membranes or remodeling of the endoplasmic reticulum. PMID:23770188

  9. Engineering of a novel Ca²⁺-regulated kinesin molecular motor using a calmodulin dimer linker.

    PubMed

    Shishido, Hideki; Maruta, Shinsaku

    2012-06-29

    The kinesin-microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have "on-off" control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355-M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355-M13 dimerization with CaM dimers, we measured K355-M13 motility and found that it can be reversibly regulated in a Ca(2+)-dependent manner. We also found that velocities of K355-M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca(2+)-dependent dimerization of K355-M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  10. Time-of-Flight Secondary Ion Mass Spectrometry based Molecular Histology of Human Spinal Cord Tissue and Motor Neurons

    PubMed Central

    Hanrieder, Jörg; Malmberg, Per; Lindberg, Olle R.; Fletcher, John S.; Ewing, Andrew G.

    2013-01-01

    Secondary ion mass spectrometry is a powerful method for imaging biological samples with high spatial resolution. Whole section ToF SIMS scans and multivariate data analysis have been performed on human spinal cord in order to delineate anatomical regions of interest based on their chemical distribution pattern. ToF SIMS analysis of thoracic spinal cord sections was performed at 5µm resolution within 2 hours. Multivariate image analysis by means of principal component analysis and maximum auto correlation factor analysis resulted in detection of more than 400 m/z peaks that were found to be significantly changed. Here, the results show characteristic biochemical distributions that are well in line with major histological regions, including grey and white matter. As an approach for iterative segmentation, we further evaluated previously outlined regions of interest as identified by multivariate image analysis. Here, further discrimination of the grey matter into ventral, lateral and dorsal neuroanatomical regions was observed. TOF SIMS imaging has been carried out at submicron resolution obtaining localization and characterization of spinal motor neurons based on their chemical fingerprint, including neurotransmitter precursors that serve as molecular indicators for motor neuron integrity. Thus, TOF SIMS can be used as an approach for chemical histology and pathology. SIMS holds immense potential for investigating the subcellular mechanisms underlying spinal cord related diseases including chronic pain and amyotrophic lateral sclerosis. PMID:23947367

  11. Molecular motors are differentially distributed on Golgi membranes from polarized epithelial cells

    PubMed Central

    1994-01-01

    Microtubules (MT) are required for the efficient transport of membranes from the trans-Golgi and for transcytosis of vesicles from the basolateral membrane to the apical cytoplasm in polarized epithelia. MTs in these cells are primarily oriented with their plus ends basally near the Golgi and their minus-ends in the apical cytoplasm. Here we report that isolated Golgi and Golgi-enriched membranes from intestinal epithelial cells possess the actin based motor myosin-I, the MT minus- end-directed motor cytoplasmic dynein and its in vitro motility activator dynactin (p150/Glued). The Golgi can be separated into stacks, possessing features of the Golgi cisternae, and small membranes enriched in the trans-Golgi network marker TGN 38/41. Whereas myosin-I is present on all membranes in the Golgi fraction, dynein is present only on the small membrane fraction. Dynein, like myosin-I, is associated with membranes as a cytoplasmic peripheral membrane protein. Dynein and myosin-I coassociate with membranes that bind to MTs and cross-link actin filaments and MTs in a nucleotide-dependent manner. We propose that cytoplasmic dynein moves Golgi membranes along MTs to the cell cortex where myosin-I provides local delivery through the actin- rich cytoskeleton to the apical membrane. PMID:8045931

  12. Michaelis-Menten at 100 and allosterism at 50: driving molecular motors in a hailstorm with noisy ATPase engines and allosteric transmission.

    PubMed

    Chowdhury, Debashish

    2014-01-01

    Cytoskeletal motor proteins move on filamentous tracks by converting input chemical energy that they derive by catalyzing the hydrolysis of ATP. The ATPase site is the analogue of an engine and hydrolysis of ATP is the analogue of burning of chemical fuel. Moreover, the functional role of a segment of the motor is analogous to that of the transmission system of an automobile, which consists of a shaft, gear, clutch, etc. The operation of the engine is intrinsically 'noisy' and the motor faces a molecular 'hailstorm' in the aqueous medium. In this commemorative review, we celebrate the centenary of Michaelis and Menten's landmark paper of 1913 and the golden jubilee of Monod and colleagues classic paper of 1963 by highlighting their relevance with respect to explaining the operational mechanisms of the engine and the transmission system, respectively, of cytoskeletal motors.

  13. INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Monte—Carlo Simulation of Multiple-Molecular-Motor Transport

    NASA Astrophysics Data System (ADS)

    Wang, Zi-Qing; Wang, Guo-Dong; Shen, Wei-Bo

    2010-10-01

    Multimotor transport is studied by Monte-Carlo simulation with consideration of motor detachment from the filament. Our work shows, in the case of low load, the velocity of multi-motor system can decrease or increase with increasing motor numbers depending on the single motor force-velocity curve. The stall force and run-length reduced greatly compared to other models. Especially in the case of low ATP concentrations, the stall force of multi motor transport even smaller than the single motor's stall force.

  14. From Computational Photobiology to the Design of Vibrationally Coherent Molecular Devices and Motors

    NASA Astrophysics Data System (ADS)

    Olivucci, Massimo

    2014-03-01

    In the past multi-configurational quantum chemical computations coupled with molecular mechanics force fields have been employed to investigate spectroscopic, thermal and photochemical properties of visual pigments. Here we show how the same computational technology can nowadays be used to design, characterize and ultimately, prepare light-driven molecular switches which mimics the photophysics of the visual pigment bovine rhodopsin (Rh). When embedded in the protein cavity the chromophore of Rh undergoes an ultrafast and coherent photoisomerization. In order to design a synthetic chromophore displaying similar properties in common solvents, we recently focused on indanylidene-pyrroline (NAIP) systems. We found that these systems display light-induced ground state coherent vibrational motion similar to the one detected in Rh. Semi-classical trajectories provide a mechanistic description of the structural changes associated to the observed coherent motion which is shown to be ultimately due to periodic changes in the π-conjugation.

  15. Direct Observation of a Dark State in the Photocycle of a Light-Driven Molecular Motor

    PubMed Central

    2016-01-01

    Controlling the excited-state properties of light driven molecular machines is crucial to achieving high efficiency and directed functionality. A key challenge in achieving control lies in unravelling the complex photodynamics and especially in identifying the role played by dark states. Here we use the structure sensitivity and high time resolution of UV-pump/IR-probe spectroscopy to build a detailed and comprehensive model of the structural evolution of light driven molecular rotors. The photodynamics of these chiral overcrowded alkene derivatives are determined by two close-lying excited electronic states. The potential energy landscape of these “bright” and “dark” states gives rise to a broad excited-state electronic absorption band over the entire mid-IR range that is probed for the first time and modeled by quantum mechanical calculations. The transient IR vibrational fingerprints observed in our studies allow for an unambiguous identification of the identity of the “dark” electronic excited state from which the photon’s energy is converted into motion, and thereby pave the way for tuning the quantum yield of future molecular rotors based on this structural motif. PMID:27684513

  16. Controlling the ratchet effect through the symmetries of the systems: application to molecular motors.

    PubMed

    Chacón, Ricardo; Quintero, Niurka R

    2007-04-01

    We discuss a novel generic mechanism for controlling the ratchet effect through the breaking of relevant symmetries. We review previous works on ratchets where directed transport is induced by the breaking of standard temporal symmetries f(t)=-f(t+T/2) and f(t)=f(-t) (or f(t)=-f(-t)). We find that in seemingly unrelated systems the average velocity (or the current) of particles (or solitons) exhibits common features. We show that, as a consequence of Curie's symmetry principle, the average velocity (or the current) is related to the breaking of the symmetries of the system. This relationship allows us to control the transport in a systematic way. The qualitative agreement between the present analytical predictions and previous experimental, numerical, and theoretical results leads us to suggest that for the given breaking of the temporal symmetries there is an optimal wave form for a given time-periodic force. Also, we comment on how this mechanism can be applied to the case where a ratchet effect is induced by breaking of spatial symmetries. Finally, we conjecture that the ratchet potential underlying biological motor proteins might be optimized according to the breaking of the relevant symmetries.

  17. Engineering of a novel Ca{sup 2+}-regulated kinesin molecular motor using a calmodulin dimer linker

    SciTech Connect

    Shishido, Hideki; Maruta, Shinsaku

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Engineered kinesin-M13 and calmodulin involving single cysteine were prepared. Black-Right-Pointing-Pointer CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. Black-Right-Pointing-Pointer Kinesin-M13 was dimerized via CaM dimer in the presence of calcium. Black-Right-Pointing-Pointer Function of the engineered kinesin was regulated by a Ca{sup 2+}-calmodulin dimer linker. -- Abstract: The kinesin-microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have 'on-off' control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355-M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355-M13 dimerization with CaM dimers, we measured K355-M13 motility and found that it can be reversibly regulated in a Ca{sup 2+}-dependent manner. We also found that velocities of K355-M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca{sup 2+}-dependent dimerization of K355-M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  18. Molecular Mapping of Movement-Associated Areas in the Avian Brain: A Motor Theory for Vocal Learning Origin

    PubMed Central

    Feenders, Gesa; Liedvogel, Miriam; Rivas, Miriam; Zapka, Manuela; Horita, Haruhito; Hara, Erina; Wada, Kazuhiro; Mouritsen, Henrik; Jarvis, Erich D.

    2008-01-01

    Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls

  19. Molecular mapping of movement-associated areas in the avian brain: a motor theory for vocal learning origin.

    PubMed

    Feenders, Gesa; Liedvogel, Miriam; Rivas, Miriam; Zapka, Manuela; Horita, Haruhito; Hara, Erina; Wada, Kazuhiro; Mouritsen, Henrik; Jarvis, Erich D

    2008-03-12

    Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls

  20. M(o)TOR of aging: MTOR as a universal molecular hypothalamus.

    PubMed

    Blagosklonny, Mikhail V

    2013-07-01

    A recent ground-breaking publication described hypothalamus-driven programmatic aging. As a Russian proverb goes "everything new is well-forgotten old". In 1958, Dilman proposed that aging and its related diseases are programmed by the hypothalamus. This theory, supported by beautiful experiments, remained unnoticed just to be re-discovered recently. Yet, it does not explain all manifestations of aging. And would organism age without hypothalamus? Do sensing pathways such as MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a "molecular hypothalamus" in every cell? Are hypothalamus-driven alterations simply a part of quasi-programmed aging manifested by hyperfunction and secondary signal-resistance? Here are some answers.

  1. Taking a molecular motor for a spin: helicase mechanism studied by spin labeling and PELDOR

    PubMed Central

    Constantinescu-Aruxandei, Diana; Petrovic-Stojanovska, Biljana; Schiemann, Olav; Naismith, James H.; White, Malcolm F.

    2016-01-01

    The complex molecular motions central to the functions of helicases have long attracted attention. Protein crystallography has provided transformative insights into these dynamic conformational changes, however important questions about the true nature of helicase configurations during the catalytic cycle remain. Using pulsed EPR (PELDOR or DEER) to measure interdomain distances in solution, we have examined two representative helicases: PcrA from superfamily 1 and XPD from superfamily 2. The data show that PcrA is a dynamic structure with domain movements that correlate with particular functional states, confirming and extending the information gleaned from crystal structures and other techniques. XPD in contrast is shown to be a rigid protein with almost no conformational changes resulting from nucleotide or DNA binding, which is well described by static crystal structures. Our results highlight the complimentary nature of PELDOR to crystallography and the power of its precision in understanding the conformational changes relevant to helicase function. PMID:26657627

  2. From molecular chaperones to membrane motors: through the lens of a mass spectrometrist

    PubMed Central

    2017-01-01

    Twenty-five years ago, we obtained our first mass spectra of molecular chaperones in complex with protein ligands and entered a new field of gas-phase structural biology. It is perhaps now time to pause and reflect, and to ask how many of our initial structure predictions and models derived from mass spectrometry (MS) datasets were correct. With recent advances in structure determination, many of the most challenging complexes that we studied over the years have become tractable by other structural biology approaches enabling such comparisons to be made. Moreover, in the light of powerful new electron microscopy methods, what role is there now for MS? In considering these questions, I will give my personal view on progress and problems as well as my predictions for future directions. PMID:28202679

  3. Molecular Genetic Analysis of Survival Motor Neuron Gene in 460 Turkish Cases with Suspicious Spinal Muscular Atrophy Disease

    PubMed Central

    RASHNONEJAD, Afrooz; ONAY, Huseyin; ATIK, Tahir; ATAN SAHIN, Ozlem; GOKBEN, Sarenur; TEKGUL, Hasan; OZKINAY, Ferda

    2016-01-01

    Objective To describe 12 yr experience of molecular genetic diagnosis of Spinal Muscular Atrophy (SMA) in 460 cases of Turkish patients. Materials & Methods A retrospective analysis was performed on data from 460 cases, referred to Medical Genetics Laboratory, Ege University’s Hospital, Izmir, Turkey, prediagnosed as SMA or with family history of SMA between 2003 and 2014. The PCR-restriction fragment length polymorphism (RFLP) and the Multiplex ligation–dependent probe amplification (MLPA) analysis were performed to detect the survival motor neuron (SMN)1 deletions and to estimate SMN1 and SMN2 gene copy numbers. Results Using PCR-RFLP test, 159 of 324 postnatal and 18 of 77 prenatal cases were detected to have SMN1 deletions. From positive samples, 88.13% had a homozygous deletion in both exon 7 and exon 8 of SMN1. Using MLPA, 54.5% of families revealed heterozygous deletions of SMN1, and 2 or 3 copies of SMN2, suggesting a healthy SMA carrier. Among patients referred for SMA testing, the annual percentage of patients diagnosed as SMA has decreased gradually from 90.62% (2003) down to 20.83% (2014). Conclusion Although PCR-RFLP method is a reliable test for SMA screening, MLPA is a necessary additional test and provide relevant data for genetic counseling of families having previously affected child. The gradual decrease in the percentage of patients molecularly diagnosed as SMA shows that clinicians have begun to use genetic tests in the differential diagnosis of muscular atrophies. Cost and availability of these genetic tests has greatly attributed to their use. PMID:27843464

  4. Synthesis of molecular motors incorporating para-phenylene-conjugated or bicyclo[2.2.2]octane-insulated electroactive groups.

    PubMed

    Vives, Guillaume; Gonzalez, Alexandre; Jaud, Joël; Launay, Jean-Pierre; Rapenne, Gwénaël

    2007-01-01

    The insulating role of the bicyclo[2.2.2]octane fragment has been theoretically evaluated by comparing the electronic coupling parameter (V(ab)) in 1,4-bis(ferrocenyl)benzene (1) and 1,4-bis(ferrocenyl)bicyclo[2.2.2]octane (2). The geometries were optimized by DFT and an extended Hückel calculation was performed to evaluate V(ab) by the dimer splitting method. The calculations showed a 12-fold decrease of the electronic coupling from 60 meV for 1 to 5 meV for 2. The second part describes the synthesis of two potential molecular motors with one incorporating the insulating bicyclo[2.2.2]octane fragment. These molecules are based on a ruthenium complex bearing a tripodal stator functionalized to be anchored onto surfaces. The ferrocenyl electroactive groups and the cyclopentadienyl (Cp) rotor are connected through a p-phenylene spacer (5) or through a spacer incorporating an insulating bicyclo[2.2.2]octane moiety (6).

  5. Elasticity of a semiflexible filament with a discontinuous tension due to a cross-link or a molecular motor

    NASA Astrophysics Data System (ADS)

    Razbin, Mohammadhosein; Benetatos, Panayotis; Zippelius, Annette

    2016-05-01

    We analyze the stretching elasticity of a wormlike chain with a tension discontinuity resulting from a Hookean spring connecting its backbone to a fixed point. The elasticity of isolated semiflexible filaments has been the subject in a significant body of literature, primarily because of its relevance to the mechanics of biological matter. In real systems, however, these filaments are usually part of supramolecular structures involving cross-linkers or molecular motors, which cause tension discontinuities. Our model is intended as a minimal structural element incorporating such a discontinuity. We obtain analytical results in the weakly bending limit of the filament, concerning its force-extension relation and the response of the two parts in which the filament is divided by the spring. For a small tension discontinuity, the linear response of the filament extension to this discontinuity strongly depends on the external tension. For large external tension f , the spring force contributes a subdominant correction ˜1 /f3 /2 to the well-known ˜1 /√{f } -dependence of the end-to-end extension.

  6. Direct observation of bis(dicarbollyl)nickel conformers in solution by fluorescence spectroscopy: an approach to redox-controlled metallacarborane molecular motors.

    PubMed

    Safronov, Alexander V; Shlyakhtina, Natalia I; Everett, Thomas A; VanGordon, Monika R; Sevryugina, Yulia V; Jalisatgi, Satish S; Hawthorne, M Frederick

    2014-10-06

    As a continuation of work on metallacarborane-based molecular motors, the structures of substituted bis(dicarbollyl)nickel complexes in Ni(III) and Ni(IV) oxidation states were investigated in solution by fluorescence spectroscopy. Symmetrically positioned cage-linked pyrene molecules served as fluorescent probes to enable the observation of mixed meso-trans/dl-gauche (pyrene monomer fluorescence) and dl-cis/dl-gauche (intramolecular pyrene excimer fluorescence with residual monomer fluorescence) cage conformations of the nickelacarboranes in the Ni(III) and Ni(IV) oxidation states, respectively. The absence of energetically disfavored conformers in solution--dl-cis in the case of nickel(III) complexes and meso-trans in the case of nickel(IV)--was demonstrated based on spectroscopic data and conformer energy calculations in solution. The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven molecular motors.

  7. Power Stroke Angular Velocity Profiles of Archaeal A-ATP Synthase Versus Thermophilic and Mesophilic F-ATP Synthase Molecular Motors.

    PubMed

    Sielaff, Hendrik; Martin, James; Singh, Dhirendra; Biuković, Goran; Grüber, Gerhard; Frasch, Wayne D

    2016-12-02

    The angular velocities of ATPase-dependent power strokes as a function of the rotational position for the A-type molecular motor A3B3DF, from the Methanosarcina mazei Gö1 A-ATP synthase, and the thermophilic motor α3β3γ, from Geobacillus stearothermophilus (formerly known as Bacillus PS3) F-ATP synthase, are resolved at 5 μs resolution for the first time. Unexpectedly, the angular velocity profile of the A-type was closely similar in the angular positions of accelerations and decelerations to the profiles of the evolutionarily distant F-type motors of thermophilic and mesophilic origins, and they differ only in the magnitude of their velocities. M. mazei A3B3DF power strokes occurred in 120° steps at saturating ATP concentrations like the F-type motors. However, because ATP-binding dwells did not interrupt the 120° steps at limiting ATP, ATP binding to A3B3DF must occur during the catalytic dwell. Elevated concentrations of ADP did not increase dwells occurring 40° after the catalytic dwell. In F-type motors, elevated ADP induces dwells 40° after the catalytic dwell and slows the overall velocity. The similarities in these power stroke profiles are consistent with a common rotational mechanism for A-type and F-type rotary motors, in which the angular velocity is limited by the rotary position at which ATP binding occurs and by the drag imposed on the axle as it rotates within the ring of stator subunits.

  8. Kinesin-2 motors transport IFT-particles, dyneins and tubulin subunits to the tips of Caenorhabditis elegans sensory cilia: relevance to vision research?

    PubMed

    Scholey, Jonathan M

    2012-12-15

    The sensory outer segments (OS) of vertebrate retinal photoreceptors, which detect photons of light, resemble the distal segments of Caenorhabditis elegans sensory cilia, which detect chemical ligands that influence the chemotactic movements of the animal. Based on fluorescence microscopy assays performed in sensory cilia of living, transgenic "wild type" and mutant C. elegans, combined with in vitro motility assays using purified motors, we have proposed that two types of kinesin-2 motor, heterotrimeric kinesin-II and homodimeric OSM-3, cooperate to build amphid and phasmid sensory cilia on chemosensory neurons. Specifically, we propose that these motors function together in a redundant manner to build the axoneme core (aka middle segments (MS)), whereas OSM-3 alone serves to build the distal segments (DS). Furthermore, our data suggest that these motors accomplish this by driving two sequential steps of anterograde transport of cargoes consisting of IFT-particles, retrograde dynein motors, and ciliary tubulin subunits, from the transition zone to the tips of the axonemal microtubules (MTs). Homologs of kinesin-II (KIF3) and OSM-3 (KIF17) are also proposed to contribute to the assembly of vertebrate photoreceptors, although how they do so is currently unclear. Here I review our work on kinesin-2 motors, intraflagellar transport (IFT) and cilium biogenesis in C. elegans sensory cilia, and comment on its possible relevance to current research on vertebrate photoreceptor cilia assembly and function.

  9. Controlled Directional Motions of Molecular Vehicles, Rotors, and Motors: From Metallic to Silicon Surfaces, a Strategy to Operate at Higher Temperatures.

    PubMed

    Chérioux, Frédéric; Galangau, Olivier; Palmino, Frank; Rapenne, Gwénaël

    2016-06-17

    In the last decade, many nanomachines with controlled molecular motions have been studied, mainly on metallic surfaces, which are easy to obtain very clean, and are stable over months. However, the studies of mechanical properties of nanomachines are mainly performed at very low temperatures, usually between 5 and 80 K, which prevents any kind of applications. In this Minireview, we will present our strategy to operate at higher temperatures, in particular through the use of semiconducting silicon surfaces. We also review our best achievements in the field through some examples of rotating molecular machines that have been designed, synthesized, and studied in our groups. On metallic surfaces, the nanovehicles are molecules with two or four triptycenes as wheels and the molecular motor is built around a ruthenium organometallic center with a piano-stool geometry and peripheric ferrocenyl groups. On semiconducting silicon surfaces, vehicles are also made from triptycene fragments and the rotor is a pentaphenylbenzene molecule.

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

    PubMed

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

    2014-12-01

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

  11. A reconsideration of the link between the energetics of water and of ATP hydrolysis energy in the power strokes of molecular motors in protein structures.

    PubMed

    Widdas, Wilfred F

    2008-09-01

    Mechanical energy from oxygen metabolism by mammalian tissues has been studied since 1837. The production of heat by mechanical work was studied by Fick in about 1860. Prior to Fick's work, energetics were revised by Joule's experiments which founded the First Law of Thermodynamics. Fenn in 1923/24 found that frog muscle contractions generated extra heat proportional to the amount of work done in shortening the muscle. This was fully consistent with the Joule, Helmholtz concept used for the First Law of Thermodynamics. The link between the energetics of water and ATP hydrolysis in molecular motors is recommended for reconsideration.

  12. A Reconsideration of the Link between the Energetics of Water and of ATP Hydrolysis Energy in the Power Strokes of Molecular Motors in Protein Structures

    PubMed Central

    Widdas, Wilfred F.

    2008-01-01

    Mechanical energy from oxygen metabolism by mammalian tissues has been studied since 1837. The production of heat by mechanical work was studied by Fick in about 1860. Prior to Fick’s work, energetics were revised by Joule’s experiments which founded the First Law of Thermodynamics. Fenn in 1923/24 found that frog muscle contractions generated extra heat proportional to the amount of work done in shortening the muscle. This was fully consistent with the Joule, Helmholtz concept used for the First Law of Thermodynamics. The link between the energetics of water and ATP hydrolysis in molecular motors is recommended for reconsideration. PMID:19325829

  13. Kinesin-2 family in vertebrate ciliogenesis

    PubMed Central

    Zhao, Chengtian; Omori, Yoshihiro; Brodowska, Katarzyna; Kovach, Peter; Malicki, Jarema

    2012-01-01

    The differentiation of cilia is mediated by kinesin-driven transport. As the function of kinesins in vertebrate ciliogenesis is poorly characterized, we decided to determine the role of kinesin-2 family motors—heterotrimeric kinesin-II and the homodimeric Kif17 kinesin—in zebrafish cilia. We report that kif17 is largely dispensable for ciliogenesis; kif17 homozygous mutant animals are viable and display subtle morphological defects of olfactory cilia only. In contrast to that, the kif3b gene, encoding a heterotrimeric kinesin subunit, is necessary for cilia differentiation in most tissues, although exceptions exist, and include photoreceptors and a subset of hair cells. Cilia of these cell types persist even in kif3b/kif17 double mutants. Although we have not observed a functional redundancy of kif3b and kif17, kif17 is able to substitute for kif3b in some cilia. In contrast to kif3b/kif17 double mutants, simultaneous interference with kif3b and kif3c leads to the complete loss of photoreceptor and hair cell cilia, revealing redundancy of function. This is in agreement with the idea that Kif3b and Kif3c motor subunits form complexes with Kif3a, but not with each other. Interestingly, kif3b mutant photoreceptor cilia differentiate with a delay, suggesting that kif3c, although redundant with kif3b at later stages of differentiation, is not active early in photoreceptor ciliogenesis. Consistent with that, the overexpression of kif3c in kif3b mutants rescues early photoreceptor cilia defects. These data reveal unexpected diversity of functional relationships between vertebrate ciliary kinesins, and show that the repertoire of kinesin motors changes in some cilia during their differentiation. PMID:22308397

  14. Functional interactions of VirB11 traffic ATPases with VirB4 and VirD4 molecular motors in type IV secretion systems.

    PubMed

    Ripoll-Rozada, Jorge; Zunzunegui, Sandra; de la Cruz, Fernando; Arechaga, Ignacio; Cabezón, Elena

    2013-09-01

    Pilus biogenesis and substrate transport by type IV secretion systems require energy, which is provided by three molecular motors localized at the base of the secretion channel. One of these motors, VirB11, belongs to the superfamily of traffic ATPases, which includes members of the type II secretion system and the type IV pilus and archaeal flagellar assembly apparatus. Here, we report the functional interactions between TrwD, the VirB11 homolog of the conjugative plasmid R388, and TrwK and TrwB, the motors involved in pilus biogenesis and DNA transport, respectively. Although these interactions remained standing upon replacement of the traffic ATPase by a homolog from a phylogenetically related conjugative system, namely, TraG of plasmid pKM101, this homolog could not replace the TrwD function for DNA transfer. This result suggests that VirB11 works as a switch between pilus biogenesis and DNA transport and reinforces a mechanistic model in which VirB11 proteins act as traffic ATPases by regulating both events in type IV secretion systems.

  15. The cellular and molecular pathology of the motor system in hereditary spastic paraparesis due to mutation of the spastin gene.

    PubMed

    Wharton, Stephen B; McDermott, Christopher J; Grierson, Andrew J; Wood, Jonathan D; Gelsthorpe, Catherine; Ince, Paul G; Shaw, Pamela J

    2003-11-01

    Hereditary spastic paraparesis (HSP) is a genetically heterogeneous disorder, the most common cause of which is mutation of the spastin gene. Recent evidence suggests a role for spastin in microtubule dynamics, but the distribution of the protein within the CNS is unknown. The core neuropathology of HSP is distal degeneration of the lateral corticospinal tract and of fasciculus gracilis, but there are few neuropathological studies of cases with a defined mutation. We aimed to determine the distribution of spastin expression in the human CNS and to investigate the cellular pathology of the motor system in HSP due to mutation of the spastin gene. Using an antibody to spastin, we have carried out immunohistochemistry on postmortem brain. We have demonstrated that spastin is a neuronal protein. It is widely expressed in the CNS so that the selectivity of the degeneration in HSP is not due to the normal cellular distribution of the protein. We have identified mutation of the spastin gene in 3 autopsy cases of HSP. Distal degeneration of long tracts in the spinal cord, consistent with a dying back axonopathy, was accompanied by a microglial reaction. The presence of novel hyaline inclusions in anterior horn cells and an alteration in immunostaining for cytoskeletal proteins and mitochondria indicates that long tract degeneration is accompanied by cytopathology in the motor system and may support a role for derangement of cytoskeletal function. All 3 cases also demonstrated evidence of tau pathology outside the motor system, suggesting that the neuropathology is not confined to the motor system in spastin-related HSP.

  16. Laboratory measurements of the heterogeneous oxidation of condensed-phase organic molecular makers for motor vehicle exhaust.

    PubMed

    Weitkamp, Emily A; Lambe, Andrew T; Donahue, Neil M; Robinson, Allen L

    2008-11-01

    Triterpanoid hopanes and steranes are petroleum biomarkers used to apportion fine particulate matter to motor vehicle emissions. To investigate the chemical stability of these compounds, aerosolized motor oil was exposed to the hydroxyl radical (OH) in a smog chamber and the reaction rate constants of hopanes, steranes, and n-alkanes were measured. The experiments were conducted across a range of atmospheric conditions including low and high relative humidity (RH) and with mixtures of lubricating oil and secondary organic aerosol. Hopanes and steranes were found to react at atmospherically significant rates across the entire range of experimental conditions; they are estimated to have lifetimes on the order of several days at average summertime OH levels. The one experimental parameter that strongly influenced the effective rate constants was RH; oxidization of hopanes and steranes was about a factor of 4 slower at 75% RH than at 10% RH. Chemical mass balance (CMB) analysis was performed to illustrate the effects of oxidation on source apportionment estimates. As the extent of oxidation increases, traditional CMB analysis increasingly underestimates the contribution of gasoline vehicles butthe diesel estimates are largely unaffected. The results demonstrate that even modest levels of oxidation can alter policy-relevant conclusions about the total and relative contribution of gasoline and diesel vehicle emissions to ambient fine particle concentrations.

  17. Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human β-cardiac myosin motor function

    PubMed Central

    Sommese, Ruth F.; Sung, Jongmin; Nag, Suman; Sutton, Shirley; Deacon, John C.; Choe, Elizabeth; Leinwand, Leslie A.; Ruppel, Kathleen; Spudich, James A.

    2013-01-01

    Cardiovascular disorders are the leading cause of morbidity and mortality in the developed world, and hypertrophic cardiomyopathy (HCM) is among the most frequently occurring inherited cardiac disorders. HCM is caused by mutations in the genes encoding the fundamental force-generating machinery of the cardiac muscle, including β-cardiac myosin. Here, we present a biomechanical analysis of the HCM-causing mutation, R453C, in the context of human β-cardiac myosin. We found that this mutation causes a ∼30% decrease in the maximum ATPase of the human β-cardiac subfragment 1, the motor domain of myosin, and a similar percent decrease in the in vitro velocity. The major change in the R453C human β-cardiac subfragment 1 is a 50% increase in the intrinsic force of the motor compared with wild type, with no appreciable change in the stroke size, as observed with a dual-beam optical trap. These results predict that the overall force of the ensemble of myosin molecules in the muscle should be higher in the R453C mutant compared with wild type. Loaded in vitro motility assay confirms that the net force in the ensemble is indeed increased. Overall, this study suggests that the R453C mutation should result in a hypercontractile state in the heart muscle. PMID:23798412

  18. On the Functional Role of the {epsilon} Subunit of the Molecular Motor F-Adenosine Triphosphatase in Lipid Membranes of Cells

    SciTech Connect

    Pikin, S. A. Loginov, E. B.

    2010-11-15

    The effect of the e subunit of the molecular motor F-adenosine triphosphatase, which is built into the lipid membrane of a cell, on the dynamics of the rotor ({gamma} subunit), with which this subunit is bound, has been qualitatively considered. It is shown that its structural and conformational features arising during the hydrolysis of 'fuel' adenosine triphosphate (ATP) molecules can be explained by the change in the potential within which the rotor is located. As the numerical calculations showed, at a low ATP concentration, the hydrolysis is accompanied by an unstable rotation of the {gamma} subunit and the related proton current. A model is proposed to describe the interaction between the {epsilon} subunit and the lipid order fluctuations caused by the membrane transition to the gel state. It is demonstrated that the rotor rotations become inhomogeneous when this interaction is enhanced with a decrease in the cell temperature.

  19. Tuning Multiple Motor Travel Via Single Motor Velocity

    PubMed Central

    Xu, Jing; Shu, Zhanyong; King, Stephen J.; Gross, Steven P.

    2012-01-01

    Microtubule-based molecular motors often work in small groups to transport cargos in cells. A key question in understanding transport (and its regulation in vivo) is to identify the sensitivity of multiple-motor-based motion to various single molecule properties. Whereas both single-motor travel distance and microtubule binding rate have been demonstrated to contribute to cargo travel, the role of single-motor velocity is yet to be explored. Here, we recast a previous theoretical study, and make explicit a potential contribution of velocity to cargo travel. We test this possibility experimentally, and demonstrate a strong negative correlation between single-motor velocity and cargo travel for transport driven by two motors. Our study thus discovers a previously unappreciated role of single-motor velocity in regulating multiple-motor transport. PMID:22672518

  20. Chemistry: No turning back for motorized molecules

    NASA Astrophysics Data System (ADS)

    Clayden, Jonathan

    2016-06-01

    Two molecular motors have been developed that use chemical energy to drive rotational motion in a single direction. The findings bring the prospect of devices powered by such motors a tantalizing step closer. See Letter p.235

  1. New insights into the function of a versatile class of membrane molecular motors from studies of Myxococcus xanthus surface (gliding) motility.

    PubMed

    Mignot, Tâm; Nöllmann, Marcelo

    2017-03-02

    Cell motility is a central function of living cells, as it empowers colonization of new environmental niches, cooperation, and development of multicellular organisms. This process is achieved by complex yet precise energy-consuming machineries in both eukaryotes and bacteria. Bacteria move on surfaces using extracellular appendages such as flagella and pili but also by a less-understood process called gliding motility. During this process, rod-shaped bacteria move smoothly along their long axis without any visible morphological changes besides occasional bending. For this reason, the molecular mechanism of gliding motility and its origin have long remained a complete mystery. An important breakthrough in the understanding of gliding motility came from single cell and genetic studies in the delta-proteobacterium Myxococcus xanthus. These early studies revealed, for the first time, the existence of bacterial Focal Adhesion complexes (FA). FAs are formed at the bacterial pole and rapidly move towards the opposite cell pole. Their attachment to the underlying surface is linked to cell propulsion, in a process similar to the rearward translocation of actomyosin complexes in Apicomplexans. The protein machinery that forms at FAs was shown to contain up to seventeen proteins predicted to localize in all layers of the bacterial cell envelope, the cytosolic face, the inner membrane (IM), the periplasmic space and the outer membrane (OM). Among these proteins, a proton-gated channel at the inner membrane was identified as the molecular motor. Thus, thrust generation requires the transduction of traction forces generated at the inner membrane through the cell envelope beyond the rigid barrier of the bacterial peptidoglycan.

  2. New insights into the function of a versatile class of membrane molecular motors from studies of Myxococcus xanthus surface (gliding) motility

    PubMed Central

    Mignot, Tâm; Nöllmann, Marcelo

    2017-01-01

    Cell motility is a central function of living cells, as it empowers colonization of new environmental niches, cooperation, and development of multicellular organisms. This process is achieved by complex yet precise energy-consuming machineries in both eukaryotes and bacteria. Bacteria move on surfaces using extracellular appendages such as flagella and pili but also by a less-understood process called gliding motility. During this process, rod-shaped bacteria move smoothly along their long axis without any visible morphological changes besides occasional bending. For this reason, the molecular mechanism of gliding motility and its origin have long remained a complete mystery. An important breakthrough in the understanding of gliding motility came from single cell and genetic studies in the delta-proteobacterium Myxococcus xanthus. These early studies revealed, for the first time, the existence of bacterial Focal Adhesion complexes (FA). FAs are formed at the bacterial pole and rapidly move towards the opposite cell pole. Their attachment to the underlying surface is linked to cell propulsion, in a process similar to the rearward translocation of actomyosin complexes in Apicomplexans. The protein machinery that forms at FAs was shown to contain up to seventeen proteins predicted to localize in all layers of the bacterial cell envelope, the cytosolic face, the inner membrane (IM), the periplasmic space and the outer membrane (OM). Among these proteins, a proton-gated channel at the inner membrane was identified as the molecular motor. Thus, thrust generation requires the transduction of traction forces generated at the inner membrane through the cell envelope beyond the rigid barrier of the bacterial peptidoglycan. PMID:28357395

  3. Motor syndromes.

    PubMed

    Corea, Francesco; Micheli, Sara

    2012-01-01

    Motor disturbances alone or associated with other focal deficits are the most common symptoms suggesting a neurovascular event. An appropriate clinical assessment of these signs and symptoms may help physicians to better diagnose and to both better treat and predict outcome. In this paper the main clinical features of motor deficit are described together with other motor-related events such as ataxia and movement disturbances.

  4. Molecular Motor MYO1C, Acetyltransferase KAT6B and Osteogenetic Transcription Factor RUNX2 Expression in Human Masseter Muscle Contributes to Development of Malocclusion

    PubMed Central

    Desh, Heather; Gray, S Lauren; Horton, Michael J; Raoul, Gwenael; Rowlerson, Anthea M; Ferri, Joel; Vieira, Alexandre R; Sciote, James J

    2014-01-01

    Objective Type I myosins are molecular motors necessary for glucose transport in the cytoplasm and initiation of transcription in the nucleus. Two of these, MYO1H and MYO1C, are paralogs which may be important in the development of malocclusion. The objective of this study was to investigate their gene expression in the masseter muscle of malocclusion subjects. Two functionally related proteins known to contribute to malocclusion were also investigated: KAT6B (a chromatin remodeling epigenetic enzyme which is activated by MYO1C) and RUNX2 (a transcription factor regulating osteogenesis which is activated by KAT6B). Design Masseter muscle samples and malocclusion classifications were obtained from orthognathic surgery subjects. Muscle was sectioned and immunostained to determine fiber type properties. RNA was isolated from the remaining sample to determine expression levels for the four genes by TaqMan® RT-PCR. Fiber type properties, gene expression quantities and malocclusion classification were compared. Results There were very significant associations (P<0.0000001) between MYO1C and KAT6B expressions. There were also significant associations (P<0.005) between RUNX2 expression and masseter muscle type II fiber properties. Very few significant associations were identified between MYO1C and masseter muscle fiber type properties. Conclusions The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodeling for gene expression. This is the nuclear myosin1 (NM1) function of MYO1C. A surprising finding is the relationship between RUNX2 and type II masseter muscle fibers, since RUNX2 expression in mature muscle was previously unknown. Further investigations are necessary to elucidate the role of RUNX2 in adult masseter muscle. PMID:24698832

  5. Molecular machinery built from DNA

    NASA Astrophysics Data System (ADS)

    Bath, Jonathan; Turberfield, Andrew J.

    2013-03-01

    DNA can be used as both construction material and fuel for molecular motors. Systems of motors and tracks can be constructed and movement of the motor along the track can be directly observed. The path that a taken by a motor as it navigates a network of tracks can be programmed by instructions that are added externally or carried by the motor itself. Such systems might be used as part molecular assembly lines that can be dynamically reconfigured in response to changing demands.

  6. The Role of Molecular Motors in the Mechanics of Active Gels and the Effects of Inertia, Hydrodynamic Interaction and Compressibility in Passive Microrheology

    DTIC Science & Technology

    2014-07-01

    to characterize are active gels. They are formed by semiflexible polymer filaments driven by motor proteins that convert chemical energy from the...a single-chain mean-field model to describe the mechanical properties of active gels. We model the semiflexible filaments as bead-spring chains and...attachment state of the filaments , and the motor-generated forces, as stochastic state variables which evolve according to a proposed differential

  7. Stepper motor

    NASA Technical Reports Server (NTRS)

    Dekramer, Cornelis

    1994-01-01

    The purpose of this document is to describe the more commonly used permanent magnet stepper motors for spaceflight. It will discuss the mechanical and electrical aspects of the devices, their torque behavior, those parameters which need to be controlled and measured, and test methods to be employed. It will also discuss torque margins, compare these to the existing margin requirements, and determine the applicability of these requirements. Finally it will attempt to generate a set of requirements which will be used in any stepper motor procurement and will fully characterize the stepper motor behavior in a consistent and repeatable fashion.

  8. Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: New insights into molecular mechanisms responsible for the disease

    SciTech Connect

    Hahnen, E.; Schoenling, J.; Zerres, K.

    1996-11-01

    Spinal muscular atrophy (SMA) is a frequent autosomal recessive neurodegenerative disorder leading to weakness and atrophy of voluntary muscles. The survival motor-neuron gene (SMN), a strong candidate for SMA, is present in two highly homologous copies (telSMN and cenSMN) within the SMA region. Only five nucleotide differences within the region between intron 6 and exon 8 distinguish these homologues. Independent of the severity of the disease, 90%-98% of all SMA patients carry homozygous deletions in telSMN, affecting either exon 7 or both exons 7 and 8. We present the molecular analysis of 42 SMA patients who carry homozygous deletions of telSMN exon 7 but not of exon 8. The question arises whether in these cases the telSMN is truncated upstream of exon 8 or whether hybrid SMN genes exist that are composed of centromeric and telomeric sequences. By a simple PCR-based assay we demonstrate that in each case the remaining telSMN exon 8 is part of a hybrid SMN gene. Sequencing of cloned hybrid SMN genes from seven patients revealed the same composition in all but two patients: the base-pair differences in introns 6 and 7 and exon 7 are of centromeric origin whereas exon 8 is of telomeric origin. Nonetheless, haplotype analysis with polymorphic multicopy markers, Ag1-CA and C212, localized at the 5{prime} end of the SMN genes, suggests different mechanisms of occurrence, unequal rearrangements, and gene conversion involving both copies of the SMN genes. In approximately half of all patients, we identified a consensus haplotype, suggesting a common origin. Interestingly, we identified a putative recombination hot spot represented by recombination-simulating elements (TGGGG and TGAGGT) in exon 8 that is homologous to the human deletion-hot spot consensus sequence in the immunoglobulin switch region, the {alpha}-globin cluster, and the polymerase {alpha} arrest sites. This may explain why independent hybrid SMN genes show identical sequences. 35 refs., 4 figs., 1 tab.

  9. Quantitative Analysis of the Feedback of the Robust Signaling Pathway Network of Myosin V Molecular Motors on GluR1 of AMPA in Neurons: A Networking Approach for Controlling Nanobiomachines

    NASA Astrophysics Data System (ADS)

    Liu, Jian-Qin; Nakano, Tadashi

    Acting as nanobiomachines within the cell, myosin V molecular motors contribute greatly to the LTP (Long Term Potentiation) in neural signaling, which transport the recycling endosomes from the dendrite to the spine of neurons and the GluR1 in AMPA receptors lead to the activities of memorization in brains. However it is unknown that how the restriction of GluR1 at the spine of neuron is caused by the signaling cascade of myosin V and Rab11/Rab11-FIP2 during the myosin V centered signaling process in neurons. Here we report that the feedback of the biochemical reaction for binding Myosin V and Rab11/Rab11-FIP2 plays a pivotal role to restrict the accumulation of GluR1 at the spine. We have investigated the feedback of myosin V and Rab11/Rab11-FIP2 on the convergence of GluR1 by using the computational model of intracellular signaling pathway networks we designed and the simulation software Cell Illustrator Professional Version 3.0 ®. The obtained results show that controllability of molecular motor based nanobiomachines is inevitable for exploring the molecular mechanism of neuroscience at the nanoscale.

  10. Genetic heterogeneity of motor neuropathies

    PubMed Central

    Bansagi, Boglarka; Griffin, Helen; Whittaker, Roger G.; Antoniadi, Thalia; Evangelista, Teresinha; Miller, James; Greenslade, Mark; Forester, Natalie; Duff, Jennifer; Bradshaw, Anna; Kleinle, Stephanie; Boczonadi, Veronika; Steele, Hannah; Ramesh, Venkateswaran; Franko, Edit; Pyle, Angela; Lochmüller, Hanns; Chinnery, Patrick F.

    2017-01-01

    Objective: To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Methods: Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). Results: The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62–2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Conclusions: Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies. PMID:28251916

  11. Advanced Motors

    SciTech Connect

    Knoth, Edward A; Chelluri, Bhanumathi; Schumaker, Edward J

    2012-12-14

    vProject Summary Transportation energy usage is predicted to increase substantially by 2020. Hybrid vehicles and fuel cell powered vehicles are destined to become more prominent as fuel prices rise with the demand. Hybrid and fuel cell vehicle platforms are both dependent on high performance electric motors. Electric motors for transportation duty will require sizeable low-speed torque to accelerate the vehicle. As motor speed increases, the torque requirement decreases which results in a nearly constant power motor output. Interior permanent magnet synchronous motors (IPMSM) are well suited for this duty. , , These rotor geometries are configured in straight lines and semi circular arc shapes. These designs are of limited configurations because of the lack of availability of permanent magnets of any other shapes at present. We propose to fabricate rotors via a novel processing approach where we start with magnet powders and compact them into a net shape rotor in a single step. Using this approach, widely different rotor designs can be implemented for efficiency. The current limitation on magnet shape and thickness will be eliminated. This is accomplished by co-filling magnet and soft iron powders at specified locations in intricate shapes using specially designed dies and automatic powder filling station. The process fundamentals for accomplishing occurred under a previous Applied Technology Program titled, Motors and Generators for the 21st Century. New efficient motor designs that are not currently possible (or cost prohibitive) can be accomplished by this approach. Such an approach to motor fabrication opens up a new dimension in motor design. Feasibility Results We were able to optimize a IPMSM rotor to take advantage of the powder co-filling and DMC compaction processing methods. The minimum low speed torque requirement of 5 N-m can be met through an optimized design with magnet material having a Br capability of 0.2 T. This level of magnetic performance can

  12. [Motor rehabilitation].

    PubMed

    Doménech, J; García-Aymerich, V; Juste, J; Ortiz, A

    2002-02-01

    The child's rehabilitation objectives are the same of the early intervention. The early intervention include motor approaches to facilitate the unique way of the newborn's expression: the movement and with it his holistic development. The motor approach is a classic aspect of early intervention but it is not itself early intervention. When the treatment objective is a term or preterm newborn or neonate the motor approach may be the principal method to facilitate perceptions experiences and basic habits. This intervention is not made with a specific physiotherapeutic technique. It is a sequential stimulation or development, without forget that the child must be taken as a whole. This point of view has special importance the first days of life and must be included in perinatal approach routines. In this paper we expose the work method of a Child Rehabilitation Team liked to a Newborn Unit.

  13. Chemistry in motion: tiny synthetic motors.

    PubMed

    Colberg, Peter H; Reigh, Shang Yik; Robertson, Bryan; Kapral, Raymond

    2014-12-16

    CONSPECTUS: Diffusion is the principal transport mechanism that controls the motion of solute molecules and other species in solution; however, the random walk process that underlies diffusion is slow and often nonspecific. Although diffusion is an essential mechanism for transport in the biological realm, biological systems have devised more efficient transport mechanisms using molecular motors. Most biological motors utilize some form of chemical energy derived from their surroundings to induce conformational changes in order to carry out specific functions. These small molecular motors operate in the presence of strong thermal fluctuations and in the regime of low Reynolds numbers, where viscous forces dominate inertial forces. Thus, their dynamical behavior is fundamentally different from that of macroscopic motors, and different mechanisms are responsible for the production of useful mechanical motion. There is no reason why our interest should be confined to the small motors that occur naturally in biological systems. Recently, micron and nanoscale motors that use chemical energy to produce directed motion by a number of different mechanisms have been made in the laboratory. These small synthetic motors also experience strong thermal fluctuations and operate in regimes where viscous forces dominate. Potentially, these motors could be directed to perform different transport tasks, analogous to those of biological motors, for both in vivo and in vitro applications. Although some synthetic motors execute conformational changes to effect motion, the majority do not, and, instead, they use other mechanisms to convert chemical energy into directed motion. In this Account, we describe how synthetic motors that operate by self-diffusiophoresis make use of a self-generated concentration gradient to drive motor motion. A description of propulsion by self-diffusiophoresis is presented for Janus particle motors comprising catalytic and noncatalytic faces. The properties

  14. Therma motor

    DOEpatents

    Kandarian, R.

    The disclosure is directed to a thermal motor utilizing two tapered prestressed parallel adjacent cylinders lengthwise disposed about one third in a coolant. Heat is applied to contacting portions of the cylinders outside the coolant to cause them to deform and turn. Heat sources such as industrial waste heat, geothermal hot water, solar radiation, etc. can be used.

  15. Motor Controllers

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Kollmorgen Corporation's Mermaid II two person submersible is propeller-driven by a system of five DC brushless motors with new electronic controllers that originated in work performed in a NASA/DOE project managed by Lewis Research Center. A key feature of the system is electric commutation rather than mechanical commutation for converting AC current to DC.

  16. The heterotrimeric kinesin-2 complex interacts with and regulates GLI protein function.

    PubMed

    Carpenter, Brandon S; Barry, Renee L; Verhey, Kristen J; Allen, Benjamin L

    2015-03-01

    GLI transport to the primary cilium and nucleus is required for proper Hedgehog (HH) signaling; however, the mechanisms that mediate these trafficking events are poorly understood. Kinesin-2 motor proteins regulate ciliary transport of cargo, yet their role in GLI protein function remains unexplored. To examine a role for the heterotrimeric KIF3A-KIF3B-KAP3 kinesin-2 motor complex in regulating GLI activity, we performed a series of structure-function analyses using biochemical, cell signaling and in vivo approaches that define novel specific interactions between GLI proteins and two components of this complex, KAP3 and KIF3A. We find that all three mammalian GLI proteins interact with KAP3 and we map specific interaction sites in both proteins. Furthermore, we find that GLI proteins interact selectively with KIF3A, but not KIF3B, and that GLI interacts synergistically with KAP3 and KIF3A. Using a combination of cell signaling assays and chicken in ovo electroporation, we demonstrate that KAP3 interactions restrict GLI activator function but not GLI repressor function. These data suggest that GLI interactions with KIF3A-KIF3B-KAP3 complexes are essential for proper GLI transcriptional activity.

  17. Locomotion of chemically powered autonomous nanowire motors

    NASA Astrophysics Data System (ADS)

    Wang, Lin; Li, Longqiu; Li, Tianlong; Zhang, Guangyu; Sun, Qian

    2015-08-01

    Physical insights on the hydrodynamics and locomotion of self-propelled nanowire motor under nonequilibrium steady state are investigated using finite element method in accordance with hybrid molecular dynamics/multiparticle collision dynamics and rigid body dynamics. Nanowire motor is discretized into finite segments, and forces of solvent molecule acting on the motor are assumed to be the sum of forces acting on all segments of the motor. We show that the locomotion of nanowire motor is mainly determined by the imbalance forces acting on the catalytic and noncatalytic segments. The average velocity along the axis increases significantly as a function of time prior to reaching equilibrium. The length of nanowire motor shows negligible effect on the velocity of the motor. Preliminary experimental results are provided to validate the current model.

  18. Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning.

    PubMed

    Jiao, Jianwei; Nakajima, Akira; Janssen, William G M; Bindokas, Vytautas P; Xiong, Xiaoli; Morrison, John H; Brorson, James R; Tang, Ya-Ping

    2008-02-27

    It is believed that gene/environment interaction (GEI) plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s) that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning.

  19. Engineering molecular machines

    NASA Astrophysics Data System (ADS)

    Erman, Burak

    2016-04-01

    Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

  20. Gross motor control

    MedlinePlus

    Gross motor control is the ability to make large, general movements (such as waving an arm or lifting a ... Gross motor control is a milestone in the development of an infant. Infants develop gross motor control before they ...

  1. Starting motor

    SciTech Connect

    Tanaka, T.; Hamano, I

    1989-05-23

    This patent describes a starting motor having a housing, planetary reduction gears including an internal gear in the housing. The improvement consists of an elastic member having a first annular portion mounted in engagement with a fixed annular member of the housing and a plurality of protruding axially extending elastic portions providing a corrugated surface pressed into engagement with an end portion of the internal gear, the elastic member being sandwiched between the internal gear and the housing member, the protruding axially extending elastic portions providing resilient means which flex and incline circumferentially under turning force from the internal gear and exert reactive thrust on the internal gear elastically so that the frictional force at the abutting surfaces of the protruding portions holds the internal gear in resilient engagement with the elastic member and the resilient means acts as a buffer to absorb rotary impact force developing in the planetary reduction gears.

  2. Molecular motor KIF17 is fundamental for memory and learning via differential support of synaptic NR2A/2B levels.

    PubMed

    Yin, Xiling; Takei, Yosuke; Kido, Mizuho A; Hirokawa, Nobutaka

    2011-04-28

    Kinesin superfamily motor protein 17 (KIF17) is a candidate transporter of N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). Disruption of the murine kif17 gene inhibits NR2B transport, accompanied by decreased transcription of nr2b, resulting in a loss of synaptic NR2B. In kif17(-/-) hippocampal neurons, the NR2A level is also decreased because of accelerated ubiquitin-proteasome system-dependent degradation. Accordingly, NMDA receptor-mediated synaptic currents, early and late long-term potentiation, long-term depression, and CREB responses are attenuated in kif17(-/-) neurons, concomitant with a hippocampus-dependent memory impairment in knockout mice. In wild-type neurons, CREB is activated by synaptic inputs, which increase the levels of KIF17 and NR2B. Thus, KIF17 differentially maintains the levels of NR2A and NR2B, and, when synapses are stimulated, the NR2B/KIF17 complex is upregulated on demand through CREB activity. These KIF17-based mechanisms for maintaining NR2A/2B levels could underlie multiple phases of memory processes in vivo.

  3. Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury

    PubMed Central

    Casanovas, Anna; Salvany, Sara; Lahoz, Víctor; Tarabal, Olga; Piedrafita, Lídia; Sabater, Raimundo; Hernández, Sara; Calderó, Jordi; Esquerda, Josep E.

    2017-01-01

    The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca2+ activated K+ [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown. We have previously suggested that neuregulin-1 (NRG1)/ErbBs-based retrograde signalling occurs at this synapse. To better understand signalling through C-boutons, we performed an analysis of the distribution of C-bouton-associated signalling proteins. We show that within SSC, S1R, Kv2.1 and NRG1 are clustered in highly specific, non-overlapping, microdomains, whereas ErbB2 and ErbB4 are present in the adjacent presynaptic compartment. This organization may define highly ordered and spatially restricted sites for different signal-transduction pathways. SSC associated proteins are disrupted in axotomised MNs together with the activation of microglia, which display a positive chemotactism to C-bouton sites. This indicates that C-bouton associated molecules are also involved in neuroinflammatory signalling in diseased MNs, emerging as new potential therapeutic targets. PMID:28065942

  4. Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury.

    PubMed

    Casanovas, Anna; Salvany, Sara; Lahoz, Víctor; Tarabal, Olga; Piedrafita, Lídia; Sabater, Raimundo; Hernández, Sara; Calderó, Jordi; Esquerda, Josep E

    2017-01-09

    The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown. We have previously suggested that neuregulin-1 (NRG1)/ErbBs-based retrograde signalling occurs at this synapse. To better understand signalling through C-boutons, we performed an analysis of the distribution of C-bouton-associated signalling proteins. We show that within SSC, S1R, Kv2.1 and NRG1 are clustered in highly specific, non-overlapping, microdomains, whereas ErbB2 and ErbB4 are present in the adjacent presynaptic compartment. This organization may define highly ordered and spatially restricted sites for different signal-transduction pathways. SSC associated proteins are disrupted in axotomised MNs together with the activation of microglia, which display a positive chemotactism to C-bouton sites. This indicates that C-bouton associated molecules are also involved in neuroinflammatory signalling in diseased MNs, emerging as new potential therapeutic targets.

  5. Motor control for a brushless DC motor

    NASA Technical Reports Server (NTRS)

    Peterson, William J. (Inventor); Faulkner, Dennis T. (Inventor)

    1985-01-01

    This invention relates to a motor control system for a brushless DC motor having an inverter responsively coupled to the motor control system and in power transmitting relationship to the motor. The motor control system includes a motor rotor speed detecting unit that provides a pulsed waveform signal proportional to rotor speed. This pulsed waveform signal is delivered to the inverter to thereby cause an inverter fundamental current waveform output to the motor to be switched at a rate proportional to said rotor speed. In addition, the fundamental current waveform is also pulse width modulated at a rate proportional to the rotor speed. A fundamental current waveform phase advance circuit is controllingly coupled to the inverter. The phase advance circuit is coupled to receive the pulsed waveform signal from the motor rotor speed detecting unit and phase advance the pulsed waveform signal as a predetermined function of motor speed to thereby cause the fundamental current waveform to be advanced and thereby compensate for fundamental current waveform lag due to motor winding reactance which allows the motor to operate at higher speeds than the motor is rated while providing optimal torque and therefore increased efficiency.

  6. Effect of the size of solvent molecules on the single-chain mechanics of poly(ethylene glycol): implications on a novel design of a molecular motor.

    PubMed

    Luo, Zhonglong; Zhang, Bo; Qian, Hu-Jun; Lu, Zhong-Yuan; Cui, Shuxun

    2016-10-20

    Excluded-volume (EV) interaction, also known as the EV effect, can drive the collapse of polymer chains in a polymer solution and promote the crystallization of polymer chains. Herein we report, for the first time, the effect of EV interaction on the single-chain mechanics of a polymer, poly(ethylene glycol) (PEG). By using AFM-based single-molecule force spectroscopy, the single-chain mechanics of a PEG chain has been detected in various nonpolar organic solvents with different molecule sizes. It is observed that the nonpolar solvents can be classified into two categories. In the small-sized organic solvents (e.g., tetrachloroethane and n-nonane), PEG presents its inherent elasticity, which is consistent with the theoretical single-chain elasticity from quantum mechanical calculations. However, in the middle-sized solvents (e.g., n-dodecane and n-hexadecane), the single-chain entropic elasticity of PEG is influenced by EV interactions noticeably, which indicates that the PEG chain tends to adopt a compact conformation under these conditions. To stretch a PEG chain from a free state to a fully extended state, more energy (1.54 kBT per repeating unit) is needed in small-sized organic solvents than in middle-sized organic solvents. It is expected that a partially stretched PEG chain would shrink to some extent when the solvent is changed from a middle-sized organic solvent to a small-sized one. Accordingly, a novel design of a PEG-based single-molecule motor that works with solvent stimuli is proposed.

  7. Wind motor

    SciTech Connect

    Biscomb, L. I.

    1985-07-09

    A spider-like carrier having at least three generally horizontal arms has a hub mounted to the vertical, rotary-axis input shaft of a load. Each arm has at least one horizontal cross-arm secured to it near its radially outer end, which is supported from the ground by a low-friction support device such as a wheel or set of wheels. Mounted on each arm at the cross-arm or cross-arms is at least one sail, vane, airfoil or similar working member which is erected or spread generally normally to the wind when the respective arm is located for the working member to be blown downwind and is feathered or headed to the wind when the respective arm is located for the working member to be driven upwind. Horizontal axis and vertical axis journalling options for the working members and various sail shapes are shown, including a concave/convex sail and motor-oriented airfoil shape which provides lift when being driven upwind are shown.

  8. A microrotary motor powered by bacteria

    NASA Astrophysics Data System (ADS)

    Hiratsuka, Yuichi; Miyata, Makoto; Tada, Tetsuya; Uyeda, Taro Q. P.

    2006-09-01

    Biological molecular motors have a number of unique advantages over artificial motors, including efficient conversion of chemical energy into mechanical work and the potential for self-assembly into larger structures, as is seen in muscle sarcomeres and bacterial and eukaryotic flagella. The development of an appropriate interface between such biological materials and synthetic devices should enable us to realize useful hybrid micromachines. Here we describe a microrotary motor composed of a 20-μm-diameter silicon dioxide rotor driven on a silicon track by the gliding bacterium Mycoplasma mobile. This motor is fueled by glucose and inherits some of the properties normally attributed to living systems. glucose | micro actuator | motor protein | nanobiotechnology | Mycoplasma gliding

  9. Na+-driven bacterial flagellar motors.

    PubMed

    Imae, Y; Atsumi, T

    1989-12-01

    Bacterial flagellar motors are the reversible rotary engine which propels the cell by rotating a helical flagellar filament as a screw propeller. The motors are embedded in the cytoplasmic membrane, and the energy for rotation is supplied by the electrochemical potential of specific ions across the membrane. Thus, the analysis of motor rotation at the molecular level is linked to an understanding of how the living system converts chemical energy into mechanical work. Based on the coupling ions, the motors are divided into two types; one is the H+-driven type found in neutrophiles such as Bacillus subtilis and Escherichia coli and the other is the Na+-driven type found in alkalophilic Bacillus and marine Vibrio. In this review, we summarize the current status of research on the rotation mechanism of the Na+-driven flagellar motors, which introduces several new aspects in the analysis.

  10. Dynamic Concentration of Motors in Microtubule Arrays

    NASA Astrophysics Data System (ADS)

    Nédélec, François; Surrey, Thomas; Maggs, A. C.

    2001-04-01

    We present experimental and theoretical studies of the dynamics of molecular motors in microtubule arrays and asters. By solving a convection-diffusion equation we find that the density profile of motors in a two-dimensional aster is characterized by continuously varying exponents. Simulations are used to verify the assumptions of the continuum model. We observe the concentration profiles of kinesin moving in quasi-two-dimensional artificial asters by fluorescent microscopy and compare with our theoretical results.

  11. Molecular hydrogen (H2) emissions and their isotopic signatures (H/D) from a motor vehicle: implications on atmospheric H2

    NASA Astrophysics Data System (ADS)

    Vollmer, M. K.; Walter, S.; Bond, S. W.; Soltic, P.; Röckmann, T.

    2010-06-01

    Molecular hydrogen (H2), its isotopic signature (deuterium/hydrogen, δD), carbon monoxide (CO), and other compounds were studied in the exhaust of a passenger car engine fuelled with gasoline or methane and run under variable air-fuel ratios and operating modes. H2 and CO concentrations were largely reduced downstream of the three-way catalytic converter (TWC) compared to levels upstream, and showed a strong dependence on the air-fuel ratio (expressed as lambda, λ). The isotopic composition of H2 ranged from δD = -140‰ to δD = -195‰ upstream of the TWC but these values decreased to -270‰ to -370‰ after passing through the TWC. Post-TWC δD values for the fuel-rich range showed a strong dependence on TWC temperature with more negative δD for lower temperatures. These effects are attributed to a rapid temperature-dependent H-D isotope equilibration between H2 and water (H2O). In addition, post TWC δD in H2 showed a strong dependence on the fraction of removed H2, suggesting isotopic enrichment during catalytic removal of H2 with enrichment factors (ɛ) ranging from -39.8‰ to -15.5‰ depending on the operating mode. Our results imply that there may be considerable variability in real-world δD emissions from vehicle exhaust, which may mainly depend on TWC technology and exhaust temperature regime. This variability is suggestive of a δD from traffic that varies over time, by season, and by geographical location. An earlier-derived integrated pure (end-member) δD from anthropogenic activities of -270‰ (Rahn et al., 2002) can be explained as a mixture of mainly vehicle emissions from cold starts and fully functional TWCs, but enhanced δD values by >50‰ are likely for regions where TWC technology is not fully implemented. Our results also suggest that a full hydrogen isotope analysis on fuel and exhaust gas may greatly aid at understanding process-level reactions in the exhaust gas, in particular in the TWC.

  12. Molecular hydrogen (H2) emissions and their isotopic signatures (H/D) from a motor vehicle: implications on atmospheric H2

    NASA Astrophysics Data System (ADS)

    Vollmer, M. K.; Walter, S.; Bond, S. W.; Soltic, P.; Röckmann, T.

    2010-02-01

    Molecular hydrogen (H2), its isotopic signature (deuterium/hydrogen, δD), carbon monoxide (CO) and other compounds were studied in the exhaust of a passenger car engine fuelled with gasoline or methane and run under variable air-fuel ratios and operating modes. H2 and CO concentrations were largely reduced downstream of the three-way catalytic converter (TWC) compared to levels upstream, and showed a strong dependence on the air-fuel ratio (expressed as lambda, λ). The isotopic composition of H2 ranged from δD=-140‰ to δD=-195‰ upstream of the TWC but these values decreased to -270‰ to -370‰ after passing through the TWC. Post-TWC δD values for the fuel-rich range showed a strong dependence on TWC temperature with more negative δD for lower temperatures. These effects are attributed to a rapid temperature-dependent H-D isotope equilibration between H2 and water (H2O). In addition, post TWC δD in H2 showed a strong dependence on the fraction of removed H2, suggesting isotopic enrichment during catalytic removal of H2 with enrichment factors (ɛ) ranging from -39.8‰ to -15.5‰ depending on the operating mode. Our results imply that there may be considerable variability in real-world δD emissions from vehicle exhaust, which may mainly depend on TWC technology and exhaust temperature regime. This variability is suggestive of a δD from traffic that varies over time, by season, and by geographical location. An earlier-derived integrated pure (end-member) δD from anthropogenic activities of -270‰ (Rahn et al., 2002) can be explained as a mixture of mainly vehicle emissions from cold starts and fully functional TWCs, but enhanced δD values by >50‰ are likely for regions where TWC technology is not fully implemented. Our results also suggest that a full hydrogen isotope analysis on fuel and exhaust gas may greatly aid at understanding process-level reactions in the exhaust gas, in particular in the TWC.

  13. Directed flux motor

    NASA Technical Reports Server (NTRS)

    Wilson, Andrew (Inventor); Punnoose, Andrew (Inventor); Strausser, Katherine (Inventor); Parikh, Neil (Inventor)

    2011-01-01

    A directed flux motor described utilizes the directed magnetic flux of at least one magnet through ferrous material to drive different planetary gear sets to achieve capabilities in six actuated shafts that are grouped three to a side of the motor. The flux motor also utilizes an interwoven magnet configuration which reduces the overall size of the motor. The motor allows for simple changes to modify the torque to speed ratio of the gearing contained within the motor as well as simple configurations for any number of output shafts up to six. The changes allow for improved manufacturability and reliability within the design.

  14. Stages of motor skill learning.

    PubMed

    Luft, Andreas R; Buitrago, Manuel M

    2005-12-01

    Successful learning of a motor skill requires repetitive training. Once the skill is mastered, it can be remembered for a long period of time. The durable memory makes motor skill learning an interesting paradigm for the study of learning and memory mechanisms. To gain better understanding, one scientific approach is to dissect the process into stages and to study these as well as their interactions. This article covers the growing evidence that motor skill learning advances through stages, in which different storage mechanisms predominate. The acquisition phase is characterized by fast (within session) and slow learning (between sessions). For a short period following the initial training sessions, the skill is labile to interference by other skills and by protein synthesis inhibition, indicating that consolidation processes occur during rest periods between training sessions. During training as well as rest periods, activation in different brain regions changes dynamically. Evidence for stages in motor skill learning is provided by experiments using behavioral, electrophysiological, functional imaging, and cellular/molecular methods.

  15. Sample solution constraints on motor-driven diagnostic nanodevices.

    PubMed

    Korten, Slobodanka; Albet-Torres, Nuria; Paderi, Francesca; ten Siethoff, Lasse; Diez, Stefan; Korten, Till; te Kronnie, Geertruy; Månsson, Alf

    2013-03-07

    The last decade has seen appreciable advancements in efforts towards increased portability of lab-on-a-chip devices by substituting microfluidics with molecular motor-based transportation. As of now, first proof-of-principle devices have analyzed protein mixtures of low complexity, such as target protein molecules in buffer solutions optimized for molecular motor performance. However, in a diagnostic work-up, lab-on-a-chip devices need to be compatible with complex biological samples. While it has been shown that such samples do not interfere with crucial steps in molecular diagnostics (for example antibody-antigen recognition), their effect on molecular motors is unknown. This critical and long overlooked issue is addressed here. In particular, we studied the effects of blood, cell lysates and solutions containing genomic DNA extracts on actomyosin and kinesin-microtubule-based transport, the two biomolecular motor systems that are most promising for lab-on-a-chip applications. We found that motor function is well preserved at defined dilutions of most of the investigated biological samples and demonstrated a molecular motor-driven label-free blood type test. Our results support the feasibility of molecular-motor driven nanodevices for diagnostic point-of-care applications and also demonstrate important constraints imposed by sample composition and device design that apply both to kinesin-microtubule and actomyosin driven applications.

  16. Enhanced conversion of syngas to liquid motor fuels

    DOEpatents

    Coughlin, Peter K.; Rabo, Jule A.

    1986-01-01

    Synthesis gas comprising carbon monoxide and hydrogen is converted to C.sub.5.sup.+ hydrocarbons suitable for use as liquid motor fuels by contact with a dual catalyst system capable of enhancing the selectivity of said conversion to motor fuel range hydrocarbons and the quality of the resulting motor fuel product. The catalyst composition employs a Fischer-Tropsch catalyst, together with a co-catalyst/support component comprising SAPO silicoaluminophosphate, non-zeolitic molecular sieve catalyst.

  17. Enhanced catalyst for conversion of syngas to liquid motor fuels

    DOEpatents

    Coughlin, Peter K.; Rabo, Jule A.

    1985-01-01

    Synthesis gas comprising carbon monoxide and hydrogen is converted to C.sub.5.sup.+ hydrocarbons suitable for use as liquid motor fuels by contact with a dual catalyst system capable of enhancing the selectivity of said conversion to motor fuel range hydrocarbons and the quality of the resulting motor fuel product. The catalyst composition employs a Fischer-Tropsch catalyst, together with a co-catalyst/support component comprising SAPO silicoaluminophosphate, non-zeolitic molecular sieve catalyst.

  18. Enhanced catalyst for conversion of syngas to liquid motor fuels

    DOEpatents

    Coughlin, P.K.; Rabo, J.A.

    1985-12-03

    Synthesis gas comprising carbon monoxide and hydrogen is converted to C[sub 5][sup +] hydrocarbons suitable for use as liquid motor fuels by contact with a dual catalyst system capable of enhancing the selectivity of said conversion to motor fuel range hydrocarbons and the quality of the resulting motor fuel product. The catalyst composition employs a Fischer-Tropsch catalyst, together with a co-catalyst/support component comprising a SAPO silicoaluminophosphate, non-zeolitic molecular sieve catalyst.

  19. Energy efficient motors

    NASA Astrophysics Data System (ADS)

    1995-01-01

    This TechData Sheet is intended to help activity personnel identify cost effective energy projects for energy efficient motors. With this guide an energy manager can identify when an energy efficient induction motor should be used.

  20. Introduction to ultrasonic motors

    SciTech Connect

    Sashida, Toshiiku; Kenjo, Takashi.

    1993-01-01

    The ultrasonic motor, invented in 1980, utilizes the piezoelectric effect in the ultrasonic frequency range to provide the motive force. (In conventional electric motors the motive force is electromagnetic.) The result is a motor with unusually good low-speed high-torque and power-to-weight characteristics. It has already found applications in camera autofocus mechanisms, medical equipment subject to high magnetic fields, and motorized car accessories. Its applications will increase as designers become more familiar with its unique characteristics. This book is the result of a collaboration between the inventor and an expert in conventional electric motors: the result is an introduction to the general theory presented in a way that links it to conventional motor theory. It will be invaluable both to motor designers and to those who design with and use electric motors as an introduction to this important new invention.

  1. Chronic motor tic disorder

    MedlinePlus

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  2. Sliding of microtubules by a team of dynein motors: Understanding the effect of spatial distribution of motor tails and mutual exclusion of motor heads on microtubules

    NASA Astrophysics Data System (ADS)

    Singh, Hanumant Pratap; Takshak, Anjneya; Mall, Utkarsh; Kunwar, Ambarish

    2016-06-01

    Molecular motors are natural nanomachines that use the free energy released from ATP hydrolysis to generate mechanical forces. Cytoplasmic dynein motors often work collectively as a team to drive important processes such as axonal growth, proplatelet formation and mitosis, as forces generated by single motors are insufficient. A large team of dynein motors is used to slide cytoskeletal microtubules with respect to one another during the process of proplatelet formation and axonal growth. These motors attach to a cargo microtubule via their tail domains, undergo the process of detachment and reattachment of their head domains on another track microtubule, while sliding the cargo microtubule along the track. Traditional continuum/mean-field approaches used in the past are not ideal for studying the sliding mechanism of microtubules, as they ignore spatial and temporal fluctuations due to different possible distributions of motor tails on cargo filament, as well as binding/unbinding of motors from their track. Therefore, these models cannot be used to address important questions such as how the distribution of motor tails on microtubules, or how the mutual exclusion of motor heads on microtubule tracks affects the sliding velocity of cargo microtubule. To answer these, here we use a computational stochastic model where we model each dynein motor explicitly. In our model, we use both random as well as uniform distributions of dynein motors on cargo microtubule, as well as mutual exclusion of motors on microtubule tracks. We find that sliding velocities are least affected by the distribution of motor tails on microtubules, whereas they are greatly affected by mutual exclusion of motor heads on microtubule tracks. We also find that sliding velocity depends on the length of cargo microtubule if mutual exclusion among motor heads is considered.

  3. The Genetic Engineering of Motor Proteins

    NASA Astrophysics Data System (ADS)

    Hartz, Rachael M.

    Molecular motors are a remarkable feature within living organisms that are responsible for directional mechanical motion, which is driven by adenosine triphosphate (ATP) hydrolysis. Actin-binding molecular motors are of specific interest in the field of nanotechnology as filamentous actin is capable of carrying cargo, such as quantum dots, while it is translocated along a motor coated surface. The binding regions of motor proteins, which are known to interact with actin, such as Myosin, have been thoroughly examined and identified. Rapid genetic engineering of the ATP-hydrolyzing enzyme, adenosine kinase, to incorporate these binding regions is possible through the use of site- directed mutagenesis. The sequences, which were mutated into the ADK wt gene, were incorporated in an unstructured loop region. During the phosphate transfer, the mutants switch between open and closed conformational states. The binding affinity of the sequences to the actin is altered during this conformational switch, thus causing the motor to move along actin filament. The ADK mutants and their interaction with filamentous actin was monitored by an in vitro motility assay. Two different mutants of ADK were found to have retained enzymatic functionality after the mutagenesis as well as function as actin-based motor proteins.

  4. Smart motor technology

    NASA Technical Reports Server (NTRS)

    Packard, D.; Schmitt, D.

    1984-01-01

    Current spacecraft design relies upon microprocessor control; however, motors usually require extensive additional electronic circuitry to interface with these microprocessor controls. An improved control technique that allows a smart brushless motor to connect directly to a microprocessor control system is described. An actuator with smart motors receives a spacecraft command directly and responds in a closed loop control mode. In fact, two or more smart motors can be controlled for synchronous operation.

  5. Piezoelectric ultrasonic motors

    SciTech Connect

    Wallaschek, J.

    1994-12-31

    Piezoelectric ultrasonic motors are a new type of actuator. They are characterized by high torque at low rotational speed, simple mechanical design and good controllability. They also provide a high holding torque even if no power is applied. Compared to electromagnetic actuators the torque per volume ratio of piezoelectric ultrasonic motors can be higher by an order of magnitude. Recently various types of piezoelectric ultrasonic motors have been developed for industrial applications. This paper describes several types of piezoelectric ultrasonic motors.

  6. Sticks in honey - Motor-connected Microtubules at low Reynolds number

    NASA Astrophysics Data System (ADS)

    Berman, Rotem S.; Leshansky, Alex; Avron, Joseph E.

    2010-11-01

    It is known that suspensions of microtubules (MTs) and molecular motors spontaneously form ordered asters and vortices. We consider the motion of MTs' assemblages connected by molecular motors at low Reynolds number. The MTs are modeled as rigid sticks and their hydrodynamic interaction with the medium is determined using slender body approximation. The motors are modeled as moving points which provide kinematic constrains for the sticks' motion. The hydrodynamic alignment of a pair of MTs for two possible motor connections is considered: a single head motor connection, in which the motor moves on one of the sticks and carries the other one, and a dual head motor connection whereas the motor advances on both sticks. We further address the formation of an aster from the vortex of inter-connected MTs. The forces the motors need to exert on the MTs in the course of closing the vortex and their dependence on the number of MTs are computed.

  7. A Reconfigurable Stepping Motor

    NASA Astrophysics Data System (ADS)

    Rogers, Charles; Selvaggi, Richard

    2009-04-01

    Multiphase brushless actuators, commonly known as the stepper motors, are ubiquitous for many precision control applications. Developments in the microelectronics have lead to their use as efficient drive motors for modern electric vehicles. Understanding the physics and the control logic for interfacing these transducers continues to be important for scientists and engineers. An overview of the stepping motor principles and interfacing requirements is presented and a simple working model used to teach the concepts of stepper motors is described and demonstrated. This model was used to design a much larger stepper motor required to precisely rotate a massive optical system in the undergraduate advanced physics laboratory.

  8. Motor/generator

    DOEpatents

    Hickam, Christopher Dale

    2008-05-13

    A motor/generator is provided for connecting between a transmission input shaft and an output shaft of a prime mover. The motor/generator may include a motor/generator housing, a stator mounted to the motor/generator housing, a rotor mounted at least partially within the motor/generator housing and rotatable about a rotor rotation axis, and a transmission-shaft coupler drivingly coupled to the rotor. The transmission-shaft coupler may include a clamp, which may include a base attached to the rotor and a plurality of adjustable jaws.

  9. Solid propellant motor

    NASA Technical Reports Server (NTRS)

    Shafer, J. I.; Marsh, H. E., Jr. (Inventor)

    1978-01-01

    A case bonded end burning solid propellant rocket motor is described. A propellant with sufficiently low modulus to avoid chamber buckling on cooling from cure and sufficiently high elongation to sustain the stresses induced without cracking is used. The propellant is zone cured within the motor case at high pressures equal to or approaching the pressure at which the motor will operate during combustion. A solid propellant motor with a burning time long enough that its spacecraft would be limited to a maximum acceleration of less than 1 g is provided by one version of the case bonded end burning solid propellant motor of the invention.

  10. Piezoceramic Ultrasonic Motor Technology

    SciTech Connect

    Burden, J.S.

    1999-02-24

    The objective of this project was to team Aerotech and AlliedSignal FM and T (AS) to develop a cost-efficient process for small-batch, high performance PZT motor production. Aerotech would acquire the basic process expertise in motor fabrication, assembly, and testing from AS. Together, Aerotech and AS were to identify appropriate process improvements, focusing on raw material quality, manufacturing processes, and durability assessment. Aerotech would then design and build a motor in consultation with AS. Aerotech engineering observed motor manufacturing in the AS piezo lab and worked side by side with AS personnel to build and test a prototype motor to facilitate learning the technology. Using information from AS and hands-on experience with the AS motor drive system enabled Aerotech to design and build its own laboratory drive system to operate motors. The team compiled information to establish a potential piezo motor users' list, and an intellectual property search was conducted to understand current patent and IP (intellectual property) status of motor design. Work was initiated to identify and develop an American source for piezo motor elements; however, due to manpower restraints created by the resignation of the AS Ph.D. ceramist responsible for these tasks, the project schedule slipped. The project was subsequently terminated before significant activities were accomplished. AS did, however, provide Aerotech with contacts in Japanese industry that are willing and capable of supplying them with special design motor elements.

  11. Motor degradation prediction methods

    SciTech Connect

    Arnold, J.R.; Kelly, J.F.; Delzingaro, M.J.

    1996-12-01

    Motor Operated Valve (MOV) squirrel cage AC motor rotors are susceptible to degradation under certain conditions. Premature failure can result due to high humidity/temperature environments, high running load conditions, extended periods at locked rotor conditions (i.e. > 15 seconds) or exceeding the motor`s duty cycle by frequent starts or multiple valve stroking. Exposure to high heat and moisture due to packing leaks, pressure seal ring leakage or other causes can significantly accelerate the degradation. ComEd and Liberty Technologies have worked together to provide and validate a non-intrusive method using motor power diagnostics to evaluate MOV rotor condition and predict failure. These techniques have provided a quick, low radiation dose method to evaluate inaccessible motors, identify degradation and allow scheduled replacement of motors prior to catastrophic failures.

  12. Motorized support jack

    DOEpatents

    Haney, Steven J.; Herron, Donald Joe

    2001-01-01

    A compact, vacuum compatible motorized jack for supporting heavy loads and adjusting their positions is provided. The motorized jack includes: (a) a housing having a base; (b) a first roller device that provides a first slidable surface and that is secured to the base; (c) a second roller device that provides a second slidable surface and that has an upper surface; (d) a wedge that is slidably positioned between the first roller device and the second roller device so that the wedge is in contact with the first slidable surface and the second slidable surface; (e) a motor; and (d) a drive mechanism that connects the motor and the wedge to cause the motor to controllably move the wedge forwards or backwards. Individual motorized jacks can support and lift of an object at an angle. Two or more motorized jacks can provide tip, tilt and vertical position adjustment capabilities.

  13. Motorized support jack

    DOEpatents

    Haney, Steven J.; Herron, Donald Joe

    2003-05-13

    A compact, vacuum compatible motorized jack for supporting heavy loads and adjusting their positions is provided. The motorized jack includes: (a) a housing having a base; (b) a first roller device that provides a first slidable surface and that is secured to the base; (c) a second roller device that provides a second slidable surface and that has an upper surface; (d) a wedge that is slidably positioned between the first roller device and the second roller device so that the wedge is in contact with the first slidable surface and the second slidable surface; (e) a motor; and (d) a drive mechanism that connects the motor and the wedge to cause the motor to controllably move the wedge forwards or backwards. Individual motorized jacks can support and lift of an object at an angle. Two or more motorized jacks can provide tip, tilt and vertical position adjustment capabilities.

  14. How molecular motors work in muscle

    NASA Astrophysics Data System (ADS)

    Huxley, Andrew

    1998-01-01

    Much of Howard's Review Article concerns the results of experiments with single myosin molecules and actin filaments. It was a huge surprise when reports of such experiments first appeared (see, for example, ref. 2), and much is being learnt from them that cannot be deduced from experiments on whole muscle fibres, whether intact or after removal of the membrane. But single-molecule experiments do not yet approach the time resolution or the freedom from brownian noise that are easily attainable on larger assemblies of myosin and actin filaments, and their interpretation is subject to many uncertainties - due, for instance, to compliance in the actin filaments and in their attachments to beads or other force-measuring components, and the attachment of myosin molecules or fragments to the base. No doubt the time course of the working stroke of a single myosin head will one day be recorded, but until that is achieved the results of experiments on whole fibres and myofibrils deserve more careful attention than has been given to them by Howard.

  15. Interacting molecular motors: Efficiency and work fluctuations

    NASA Astrophysics Data System (ADS)

    Slanina, František

    2009-12-01

    We investigate the model of “reversible ratchet” with interacting particles, presented by us earlier [F. Slanina, EPL 84, 50009 (2008)]. We further clarify the effect of efficiency enhancement due to interaction and show that it is of energetic origin, rather than a consequence of reduced fluctuations. We also show complicated structures emerging in the interaction and density dependence of the current and response function. The fluctuation properties of the work and input energy indicate in detail the far-from-equilibrium nature of the dynamics.

  16. Dissociating motor cortex from the motor

    PubMed Central

    Schieber, Marc H

    2011-01-01

    Abstract During closed-loop control of a brain–computer interface, neurons in the primary motor cortex can be intensely active even though the subject may be making no detectable movement or muscle contraction. How can neural activity in the primary motor cortex become dissociated from the movements and muscles of the native limb that it normally controls? Here we examine circumstances in which motor cortex activity is known to dissociate from movement – including mental imagery, visuo-motor dissociation and instructed delay. Many such motor cortex neurons may be related to muscle activity only indirectly. Furthermore, the integration of thousands of synaptic inputs by individual α-motoneurons means that under certain circumstances even cortico-motoneuronal cells, which make monosynaptic connections to α-motoneurons, can become dissociated from muscle activity. The natural ability of motor cortex neurons under voluntarily control to become dissociated from bodily movement may underlie the utility of this cortical area for controlling brain–computer interfaces. PMID:22005673

  17. Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA.

    PubMed

    Kawahara, Yukio; Sun, Hui; Ito, Kyoko; Hideyama, Takuto; Aoki, Masashi; Sobue, Gen; Tsuji, Shoji; Kwak, Shin

    2006-01-01

    Deficient RNA editing of the AMPA receptor subunit GluR2 at the Q/R site is a primary cause of neuronal death and recently has been reported to be a tightly linked etiological cause of motor neuron death in sporadic amyotrophic lateral sclerosis (ALS). We quantified the RNA editing efficiency of the GluR2 Q/R site in single motor neurons of rats transgenic for mutant human Cu/Zn-superoxide dismutase (SOD1) as well as patients with spinal and bulbar muscular atrophy (SBMA), and found that GluR2 mRNA was completely edited in all the motor neurons examined. It seems likely that the death cascade is different among the dying motor neurons in sporadic ALS, familial ALS with mutant SOD1 and SBMA.

  18. Theory of self-assembly of microtubules and motors.

    SciTech Connect

    Aranson, I. S.; Tsimring, L. S.; Materials Science Division; Univ. California at San Diego

    2006-01-01

    We derive a model describing spatiotemporal organization of an array of microtubules interacting via molecular motors. Starting from a stochastic model of inelastic polar rods with a generic anisotropic interaction kernel, we obtain a set of equations for the local rods concentration and orientation. At large enough mean density of rods and concentration of motors, the model describes an orientational instability. We demonstrate that the orientational instability leads to the formation of vortices and (for large density and/or kernel anisotropy) asters seen in recent experiments. We derive the specific form of the interaction kernel from the detailed analysis of microscopic interaction of two filaments mediated by a moving molecular motor and extend our results to include variable motor density and motor attachment to the substrate.

  19. Theory of self-assembly of microtubules and motors

    NASA Astrophysics Data System (ADS)

    Aranson, Igor S.; Tsimring, Lev S.

    2006-09-01

    We derive a model describing spatiotemporal organization of an array of microtubules interacting via molecular motors. Starting from a stochastic model of inelastic polar rods with a generic anisotropic interaction kernel, we obtain a set of equations for the local rods concentration and orientation. At large enough mean density of rods and concentration of motors, the model describes an orientational instability. We demonstrate that the orientational instability leads to the formation of vortices and (for large density and/or kernel anisotropy) asters seen in recent experiments. We derive the specific form of the interaction kernel from the detailed analysis of microscopic interaction of two filaments mediated by a moving molecular motor and extend our results to include variable motor density and motor attachment to the substrate.

  20. Piezoelectric Motors and Transformers

    NASA Astrophysics Data System (ADS)

    Uchino, K.

    Piezoelectric ceramics forms a new field between electronic and structural ceramics [1-4]. Application fields are classified into three categories: positioners, motors, and vibration suppressors. From the market research result for 80 Japanese component industries in 1992, tiny motors in the range of 5-8 mm are required in large numbers for office and portable equipment; the conventional electromagnetic (EM) motors are rather difficult to produce in this size with sufficient energy efficiency, while Silicon MEMS actuators are too small to be used in practice. Piezoelectric ultrasonic motors whose efficiency is insensitive to size are superior in the millimeter motor area. The manufacturing precision of optical instruments such as lasers and cameras, and the positioning accuracy for fabricating semiconductor chips are of the order of 0.1μm which is much smaller than the backlash of the EM motors. Vibration suppression in space structures and military vehicles also require compact but mighty piezoelectric actuators.

  1. Molecule concept nanocars: chassis, wheels, and motors?

    PubMed

    Joachim, Christian; Rapenne, Gwénael

    2013-01-22

    The design, synthesis, and running of a molecular nanovehicle on a surface assisted by proper nanocommunication channels for feeding and guiding the vehicle now constitute an active field of research and are no longer a nano-joke. In this Perspective, we describe how this field began, its growth, and problems to be solved. Better molecular wheels, a molecular motor with its own gears assembling for torque transmission must be mounted on (i.e., chemically bonded to) a good molecular chassis for the resulting covalently constructed molecular nanovehicle to run on a surface in a controlled manner at the atomic scale. We propose a yearly molecule concept nanocar contest to boost molecular nanovehicle research.

  2. Cryogenic Electric Motor Tested

    NASA Technical Reports Server (NTRS)

    Brown, Gerald V.

    2004-01-01

    Technology for pollution-free "electric flight" is being evaluated in a number of NASA Glenn Research Center programs. One approach is to drive propulsive fans or propellers with electric motors powered by fuel cells running on hydrogen. For large transport aircraft, conventional electric motors are far too heavy to be feasible. However, since hydrogen fuel would almost surely be carried as liquid, a propulsive electric motor could be cooled to near liquid hydrogen temperature (-423 F) by using the fuel for cooling before it goes to the fuel cells. Motor windings could be either superconducting or high purity normal copper or aluminum. The electrical resistance of pure metals can drop to 1/100th or less of their room-temperature resistance at liquid hydrogen temperature. In either case, super or normal, much higher current density is possible in motor windings. This leads to more compact motors that are projected to produce 20 hp/lb or more in large sizes, in comparison to on the order of 2 hp/lb for large conventional motors. High power density is the major goal. To support cryogenic motor development, we have designed and built in-house a small motor (7-in. outside diameter) for operation in liquid nitrogen.

  3. Sensorless, online motor diagnostics

    SciTech Connect

    Kliman, G.B.; Premerlani, W.J.; Yazici, B.; Koegl, R.A.; Mazereeuw, J.

    1997-04-01

    Electric motors play a very important role in the safe and efficient running of any industrial plant. Early detection of abnormalities in the motors will help avoid expensive failures. Motor current signature analysis (MCSA) implemented in a computer-based motor monitor can contribute to such condition-based maintenance functions. Such a system may also detect an abnormality in the process as well as the motor. Extensive online monitoring of the motors can lead to greater plant availability, extended plant life, higher quality product, and smoother plant operation. With advances in digital technology over the last several years, adequate data processing capability is now available on cost-effective, microprocessor-based, protective-relay platforms to monitor motors for a variety of abnormalities in addition to the normal protection functions. Such multifunction monitors, first introduced by Multilin, are displacing the multiplicity of electromechanical devices commonly applied for many years. Following some background information on motor monitoring, this article features recent developments in providing tools for the diagnosis of faults or incipient faults in electric motor drives: Sensorless torque measurement, direct detection of turn-to-turn short circuits, detection of cracked or broken rotor bars, and detection of bearing deterioration.

  4. Hybrid vehicle motor alignment

    DOEpatents

    Levin, Michael Benjamin

    2001-07-03

    A rotor of an electric motor for a motor vehicle is aligned to an axis of rotation for a crankshaft of an internal combustion engine having an internal combustion engine and an electric motor. A locator is provided on the crankshaft, a piloting tool is located radially by the first locator to the crankshaft. A stator of the electric motor is aligned to a second locator provided on the piloting tool. The stator is secured to the engine block. The rotor is aligned to the crankshaft and secured thereto.

  5. Self-assembly of microtubules and motors

    NASA Astrophysics Data System (ADS)

    Aranson, Igor; Tsimring, Lev

    2005-03-01

    We derive a model describing spatio-temporal assembly of an array of microtubules interacting via molecular motors. Starting from a stochastic model of inelastic polar rods with a generic anisotropic interaction kernel we obtain a set of equations for the local rods concentration and orientation. At large enough mean density of rods and concentration of motors, the model describes orientational instability. We demonstrate that the orientational instability leads to the formation of vortices and (for large density and/or kernel anisotropy) asters seen in recent experiments.

  6. Self-organization of microtubules and motors.

    SciTech Connect

    Aranson, I. S.; Tsimring, L. S.; Materials Science Division; Univ. of California at San Diego

    2006-01-01

    Here we introduce a model for spatio-temporal self-organization of an ensemble of microtubules interacting via molecular motors. Starting from a generic stochastic model of inelastic polar rods with an anisotropic interaction kernel we derive a set of equations for the local rods concentration and orientation. At large enough mean density of rods and concentration of motors, the model describes orientational instability. We demonstrate that the orientational instability leads to the formation of vortices and (for large density and/or kernel anisotropy) asters seen in recent experiments. The corresponding phase diagram of vortexasters transitions is in qualitative agreement with experiment.

  7. Roles of the orexin system in central motor control.

    PubMed

    Hu, Bo; Yang, Nian; Qiao, Qi-Cheng; Hu, Zhi-An; Zhang, Jun

    2015-02-01

    The neuropeptides orexin-A and orexin-B are produced by one group of neurons located in the lateral hypothalamic/perifornical area. However, the orexins are widely released in entire brain including various central motor control structures. Especially, the loss of orexins has been demonstrated to associate with several motor deficits. Here, we first summarize the present knowledge that describes the anatomical and morphological connections between the orexin system and various central motor control structures. In the next section, the direct influence of orexins on related central motor control structures is reviewed at molecular, cellular, circuitry, and motor activity levels. After the summarization, the characteristic and functional relevance of the orexin system's direct influence on central motor control function are demonstrated and discussed. We also propose a hypothesis as to how the orexin system orchestrates central motor control in a homeostatic regulation manner. Besides, the importance of the orexin system's phasic modulation on related central motor control structures is highlighted in this regulation manner. Finally, a scheme combining the homeostatic regulation of orexin system on central motor control and its effects on other brain functions is presented to discuss the role of orexin system beyond the pure motor activity level, but at the complex behavioral level.

  8. Models of motor-assisted transport of intracellular particles.

    PubMed Central

    Smith, D A; Simmons, R M

    2001-01-01

    One-dimensional models are presented for the macroscopic intracellular transport of vesicles and organelles by molecular motors on a network of aligned intracellular filaments. A motor-coated vesicle or organelle is described as a diffusing particle binding intermittently to filaments, when it is transported at the motor velocity. Two models are treated in detail: 1) a unidirectional model, where only one kind of motor is operative and all filaments have the same polarity; and 2) a bidirectional model, in which filaments of both polarities exist (for example, a randomly polarized actin network for myosin motors) and/or particles have plus-end and minus-end motors operating on unipolar filaments (kinesin and dynein on microtubules). The unidirectional model provides net particle transport in the absence of a concentration gradient. A symmetric bidirectional model, with equal mixtures of filament polarities or plus-end and minus-end motors of the same characteristics, provides rapid transport down a concentration gradient and enhanced dispersion of particles from a point source by motor-assisted diffusion. Both models are studied in detail as a function of the diffusion constant and motor velocity of bound particles, and their rates of binding to and detachment from filaments. These models can form the basis of more realistic models for particle transport in axons, melanophores, and the dendritic arms of melanocytes, in which networks of actin filaments and microtubules coexist and motors for both types of filament are implicated. PMID:11159382

  9. Kinesin family 17 (osmotic avoidance abnormal-3) is dispensable for photoreceptor morphology and function

    PubMed Central

    Jiang, Li; Tam, Beatrice M.; Ying, Guoxing; Wu, Sen; Hauswirth, William W.; Frederick, Jeanne M.; Moritz, Orson L.; Baehr, Wolfgang

    2015-01-01

    In Caenorhabditis elegans, homodimeric [kinesin family (KIF) 17, osmotic avoidance abnormal-3 (OSM-3)] and heterotrimeric (KIF3) kinesin-2 motors are required to establish sensory cilia by intraflagellar transport (IFT) where KIF3 and KIF17 cooperate to build the axoneme core and KIF17 builds the distal segments. However, the function of KIF17 in vertebrates is unresolved. We expressed full-length and motorless KIF17 constructs in mouse rod photoreceptors using adeno-associated virus in Xenopus laevis rod photoreceptors using a transgene and in ciliated IMCD3 cells. We found that tagged KIF17 localized along the rod outer segment axoneme when expressed in mouse and X. laevis photoreceptors, whereas KIF3A was restricted to the proximal axoneme. Motorless KIF3A and KIF17 mutants caused photoreceptor degeneration, likely through dominant negative effects on IFT. KIF17 mutant lacking the motor domain translocated to nuclei after exposure of a C-terminal nuclear localization signal. Germ-line deletion of Kif17 in mouse did not affect photoreceptor function. A rod-specific Kif3/Kif17 double knockout mouse demonstrated that KIF17 and KIF3 do not act synergistically and did not prevent rhodopsin trafficking to rod outer segments. In summary, the nematode model of KIF3/KIF17 cooperation apparently does not apply to mouse photoreceptors in which the photosensory cilium is built exclusively by KIF3.—Jiang, L., Tam, B. M., Ying, G., Wu, S., Hauswirth, W. W., Frederick, J. M., Moritz, O. L., Baehr, W. Kinesin family 17 (osmotic avoidance abnormal-3) is dispensable for photoreceptor morphology and function. PMID:26229057

  10. Advanced Motor and Motor Control Development

    DTIC Science & Technology

    1988-08-01

    dc motor with electronic controller over a wide load and speed range was demonstrated. A centrifugal pump was used as the loading mechanism and hydraulic fluid was pumped in simulation of an aircraft engine fuel pump requirement. A motor speed of 45,000 rpm was reached and a maximum output of 68.5 hp was demonstrated. The response of the system to step commands for speed change was established. Reduction of size and weight of electronic control was established as a primary future goal. The program system concept with minor rotating machine improvements is viable for

  11. Information on stepping motors

    NASA Astrophysics Data System (ADS)

    Fongarland, G.

    1982-04-01

    The principles of the stepping motors which are often used in servomechanisms are reviewed. Variable reluctance as well as permanent magnet stepping motors are considered. Their operation is explained which includes permanent rotation, starting, stopping, and resonance effects. Several application examples, drawn from problems in automation, are outlined.

  12. Stepping motor controller

    DOEpatents

    Bourret, Steven C.; Swansen, James E.

    1984-01-01

    A stepping motor is microprocessingly controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.

  13. Stepping motor controller

    DOEpatents

    Bourret, S.C.; Swansen, J.E.

    1982-07-02

    A stepping motor is microprocessor controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.

  14. Induction motor control

    NASA Astrophysics Data System (ADS)

    Hansen, Irving G.

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  15. Induction motor control

    NASA Technical Reports Server (NTRS)

    Hansen, Irving G.

    1990-01-01

    Electromechanical actuators developed to date have commonly utilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilizes induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  16. Induction motor control

    NASA Technical Reports Server (NTRS)

    Hansen, Irving G.

    1990-01-01

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  17. ISRO's solid rocket motors

    NASA Astrophysics Data System (ADS)

    Nagappa, R.; Kurup, M. R.; Muthunayagam, A. E.

    1989-08-01

    Solid rocket motors have been the mainstay of ISRO's sounding rockets and the first generation satellite launch vehicles. For the new launch vehicle under development also, the solid rocket motors contribute significantly to the vehicle's total propulsive power. The rocket motors in use and under development have been developed for a variety of applications and range in size from 30 mm dia employing 450 g of solid propellant—employed for providing a spin to the apogee motors—to the giant 2.8 m dia motor employing nearly 130 tonnes of solid propellant. The initial development, undertaken in 1967 was of small calibre motor of 75 mm dia using a double base charge. The development was essentially to understand the technological elements. Extruded aluminium tubes were used as a rocket motor casing. The fore and aft closures were machined from aluminium rods. The grain was a seven-pointed star with an enlargement of the port at the aft end and was charged into the chamber using a polyester resin system. The nozzle was a metallic heat sink type with graphite throat insert. The motor was ignited with a black powder charge and fired for 2.0 s. Subsequent to this, further developmental activities were undertaken using PVC plastisol based propellants. A class of sounding rockets ranging from 125 to 560 mm calibre were realized. These rocket motors employed improved designs and had delivered lsp ranging from 2060 to 2256 Ns/kg. Case bonding could not be adopted due to the higher cure temperatures of the plastisol propellants but improvements were made in the grain charging techniques and in the design of the igniters and the nozzle. Ablative nozzles based on asbestos phenolic and silica phenolic with graphite inserts were used. For the larger calibre rocket motors, the lsp could be improved by metallic additives. In the early 1970s designs were evolved for larger and more efficient motors. A series of 4 motors for the country's first satellite launch vehicle SLV-3 were

  18. Motor Priming in Neurorehabilitation

    PubMed Central

    Stoykov, Mary Ellen; Madhavan, Sangeetha

    2014-01-01

    Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few are practical for the current clinical environment, and the optimal priming modalities for specific clinical presentations are not known. Accordingly, developing an understanding of the various types of motor priming paradigms and their underlying neural mechanisms is an important step for therapists in neurorehabilitation. Most importantly, an understanding of the methods and their underlying mechanisms is essential for optimizing rehabilitation outcomes. The future of neurorehabilitation is likely to include these priming methods, which are delivered prior to or in conjunction with primary neurorehabilitation therapies. In this Special Interest article we discuss those priming paradigms that are supported by the greatest amount of evidence including: (i) stimulation-based priming, (ii) motor imagery and action observation, (iii) sensory priming, (iv) movement-based priming, and (v) pharmacological priming. PMID:25415551

  19. Self-organization of microtubules and motors

    NASA Astrophysics Data System (ADS)

    Ndlec, F. J.; Surrey, T.; Maggs, A. C.; Leibler, S.

    1997-09-01

    Cellular structures are established and maintained through a dynamic interplay between assembly and regulatory processes. Self-organization of molecular components provides a variety of possible spatial structures: the regulatory machinery chooses the most appropriate to express a given cellular function. Here we study the extent and the characteristics of self-organization using microtubules and molecular motors as a model system. These components are known to participate in the formation of many cellular structures, such as the dynamic asters found in mitotic and meiotic spindles. Purified motors and microtubules have previously been observed to form asters in vitro. We have reproduced this result with a simple system consisting solely of multi-headed constructs of the motor protein kinesin and stabilized microtubules. We show that dynamic asters can also be obtained from a homogeneous solution of tubulin and motors. By varying the relative concentrations of the components, we obtain a variety of self-organized structures. Further, by studying this process in a constrained geometry of micro-fabricated glass chambers, we demonstrate that the same final structure can be reached through different assembly `pathways'.

  20. Proteostasis and Diseases of the Motor Unit

    PubMed Central

    Rinaldi, Carlo; Mäger, Imre; Wood, Matthew J.

    2016-01-01

    The accumulation in neurons of aberrant protein species, the pathological hallmark of many neurodegenerative diseases, results from a global impairment of key cellular processes governing protein synthesis/degradation and repair mechanisms, also known as the proteostasis network (PN). The growing number of connections between dysfunction of this intricate network of pathways and diseases of the motor unit, where both motor neurons and muscle are primarily affected, has provided momentum to investigate the muscle- and motor neuron-specific response to physiological and pathological stressors and to explore the therapeutic opportunities that manipulation of this process may offer. Furthermore, these diseases offer an unparalleled opportunity to deepen our understanding of the molecular mechanisms behind the intertissue communication and transfer of signals of proteostasis. The most compelling aspect of these investigations is their immediate potential for therapeutic impact: targeting muscle to stem degeneration of the motor unit would represent a dramatic paradigm therapeutic shift for treating these devastating diseases. Here we will review the current state of the art of the research on the alterations of the PN in diseases of the motor unit and its potential to result in effective treatments for these devastating neuromuscular disorders. PMID:28082869

  1. Physics of protein motility and motor proteins

    NASA Astrophysics Data System (ADS)

    Kolomeisky, Anatoly B.

    2013-09-01

    Motor proteins are enzymatic molecules that transform chemical energy into mechanical motion and work. They are critically important for supporting various cellular activities and functions. In the last 15 years significant progress in understanding the functioning of motor proteins has been achieved due to revolutionary breakthroughs in single-molecule experimental techniques and strong advances in theoretical modelling. However, microscopic mechanisms of protein motility are still not well explained, and the collective efforts of many scientists are needed in order to solve these complex problems. In this special section the reader will find the latest advances on the difficult road to mapping motor proteins dynamics in various systems. Recent experimental developments have allowed researchers to monitor and to influence the activity of single motor proteins with a high spatial and temporal resolution. It has stimulated significant theoretical efforts to understand the non-equilibrium nature of protein motility phenomena. The latest results from all these advances are presented and discussed in this special section. We would like to thank the scientists from all over the world who have reported their latest research results for this special section. We are also grateful to the staff and editors of Journal of Physics: Condensed Matter for their invaluable help in handling all the administrative and refereeing activities. The field of motor proteins and protein motility is fast moving, and we hope that this collection of articles will be a useful source of information in this highly interdisciplinary area. Physics of protein motility and motor proteins contents Physics of protein motility and motor proteinsAnatoly B Kolomeisky Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116 Yuan Zhang, Mirkó Palla, Andrew Sun and Jung-Chi Liao The load dependence of the physical properties of a molecular motor

  2. System and method for motor parameter estimation

    DOEpatents

    Luhrs, Bin; Yan, Ting

    2014-03-18

    A system and method for determining unknown values of certain motor parameters includes a motor input device connectable to an electric motor having associated therewith values for known motor parameters and an unknown value of at least one motor parameter. The motor input device includes a processing unit that receives a first input from the electric motor comprising values for the known motor parameters for the electric motor and receive a second input comprising motor data on a plurality of reference motors, including values for motor parameters corresponding to the known motor parameters of the electric motor and values for motor parameters corresponding to the at least one unknown motor parameter value of the electric motor. The processor determines the unknown value of the at least one motor parameter from the first input and the second input and determines a motor management strategy for the electric motor based thereon.

  3. Advanced motor and motor control development

    NASA Astrophysics Data System (ADS)

    Wuertz, Kenneth L.; Beauchamp, Edward D.

    1988-08-01

    The capability of operating a high speed permanent magnet brushless dc motor with electronic controller over a wide load and speed range was demonstrated. A centrifugal pump was used as the loading mechanism and hydraulic fluid was pumped in simulation of an aircraft engine fuel pump requirement. A motor speed of 45,000 rpm was reached and a maximum output of 68.5 hp was demonstrated. The response of the system to step commands for speed change was established. Reduction of size and weight of electronic control was established as a primary future goal. The program system concept with minor rotating machine improvements is viable for high speed drive applications up to 100-hp level.

  4. Motor Vehicle Safety

    MedlinePlus

    ... these crashes is one part of motor vehicle safety. Here are some things you can do to ... speed or drive aggressively Don't drive impaired Safety also involves being aware of others. Share the ...

  5. Booster separation motor

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The design, development, fabrication, testing, evaluation and flight qualification of the space shuttle booster separation motor is discussed. Delivery of flight hardware to support the research and development flights of the space shuttle is discussed.

  6. MotorWeek

    ScienceCinema

    None

    2016-07-12

    In 2008, PBS's MotorWeek, television's original automotive magazine, visited Argonne's Transportation Technology R&D Center "to learn what it really takes to make clean power sources a viable reality."

  7. MotorWeek

    SciTech Connect

    2009-01-01

    In 2008, PBS's MotorWeek, television's original automotive magazine, visited Argonne's Transportation Technology R&D Center "to learn what it really takes to make clean power sources a viable reality."

  8. Piezoelectric Rotary Tube Motor

    NASA Technical Reports Server (NTRS)

    Fisher, Charles D.; Badescu, Mircea; Braun, David F.; Culhane, Robert

    2011-01-01

    A custom rotary SQUIGGLE(Registered TradeMark) motor has been developed that sets new benchmarks for small motor size, high position resolution, and high torque without gear reduction. Its capabilities cannot be achieved with conventional electromagnetic motors. It consists of piezoelectric plates mounted on a square flexible tube. The plates are actuated via voltage waveforms 90 out of phase at the resonant frequency of the device to create rotary motion. The motors were incorporated into a two-axis postioner that was designed for fiber-fed spectroscopy for ground-based and space-based projects. The positioner enables large-scale celestial object surveys to take place in a practical amount of time.

  9. High Power Density Motors

    NASA Technical Reports Server (NTRS)

    Kascak, Daniel J.

    2004-01-01

    With the growing concerns of global warming, the need for pollution-free vehicles is ever increasing. Pollution-free flight is one of NASA's goals for the 21" Century. , One method of approaching that goal is hydrogen-fueled aircraft that use fuel cells or turbo- generators to develop electric power that can drive electric motors that turn the aircraft's propulsive fans or propellers. Hydrogen fuel would likely be carried as a liquid, stored in tanks at its boiling point of 20.5 K (-422.5 F). Conventional electric motors, however, are far too heavy (for a given horsepower) to use on aircraft. Fortunately the liquid hydrogen fuel can provide essentially free refrigeration that can be used to cool the windings of motors before the hydrogen is used for fuel. Either High Temperature Superconductors (HTS) or high purity metals such as copper or aluminum may be used in the motor windings. Superconductors have essentially zero electrical resistance to steady current. The electrical resistance of high purity aluminum or copper near liquid hydrogen temperature can be l/lOO* or less of the room temperature resistance. These conductors could provide higher motor efficiency than normal room-temperature motors achieve. But much more importantly, these conductors can carry ten to a hundred times more current than copper conductors do in normal motors operating at room temperature. This is a consequence of the low electrical resistance and of good heat transfer coefficients in boiling LH2. Thus the conductors can produce higher magnetic field strengths and consequently higher motor torque and power. Designs, analysis and actual cryogenic motor tests show that such cryogenic motors could produce three or more times as much power per unit weight as turbine engines can, whereas conventional motors produce only 1/5 as much power per weight as turbine engines. This summer work has been done with Litz wire to maximize the current density. The current is limited by the amount of heat it

  10. Rocket Motor Microphone Investigation

    NASA Technical Reports Server (NTRS)

    Pilkey, Debbie; Herrera, Eric; Gee, Kent L.; Giraud, Jerom H.; Young, Devin J.

    2010-01-01

    At ATK's facility in Utah, large full-scale solid rocket motors are tested. The largest is a five-segment version of the reusable solid rocket motor, which is for use on the Ares I launch vehicle. As a continuous improvement project, ATK and BYU investigated the use of microphones on these static tests, the vibration and temperature to which the instruments are subjected, and in particular the use of vent tubes and the effects these vents have at low frequencies.

  11. Motor Energy Conservation Measures

    SciTech Connect

    Ian Metzger, Jesse Dean

    2010-12-31

    This software requires inputs of simple motor inventory information and calculates the energy and cost benefits of various retrofit opportunities. This tool includes energy conservation measures for: High Efficiency Motor retrofit and Cogged V-belts retrofit. This tool calculates energy savings, demand reduction, cost savings, and building life cycle costs including: simple payback, discounted payback, net-present value, and savings to investment ratio. In addition this tool also displays the environmental benefits of a project.

  12. Maintaining Motor Skill Performance

    DTIC Science & Technology

    1982-06-18

    trials eacb--ac--yIecon- ,, :;. - taed p- --d-t-trias,--P-t- rilk --r. expermenter-difie-d- ovementu con- strained by the stop. The distance between...processing in motor control-i ... and -laIg- e-rr--’- cae -clrsj--98 I Y. ag.L., K. A., & D5oWe-l, M. R. Serial-position effects in motor short-! term

  13. Development Motor-8

    NASA Technical Reports Server (NTRS)

    1980-01-01

    One of the key tests in the effort to return the Space Shuttle to flight following the Challenger accident was testing the development Motor-8 (DM-8). The 126-foot long, 1.2-million-pound motor, designated DM-8, underwent a full-duration horizontal test firing for two minutes at the Thiokol test facility in Utah. It was fitted with more than 500 instruments to measure such things as acceleration, pressure, deflection thrust, strain, temperature, and electrical properties.

  14. Electric vehicle motors and controllers

    NASA Technical Reports Server (NTRS)

    Secunde, R. R.

    1981-01-01

    Improved and advanced components being developed include electronically commutated permanent magnet motors of both drum and disk configuration, an unconventional brush commutated motor, and ac induction motors and various controllers. Test results on developmental motors, controllers, and combinations thereof indicate that efficiencies of 90% and higher for individual components, and 80% to 90% for motor/controller combinations can be obtained at rated power. The simplicity of the developmental motors and the potential for ultimately low cost electronics indicate that one or more of these approaches to electric vehicle propulsion may eventually displace presently used controllers and brush commutated dc motors.

  15. A Delicate Nanoscale Motor Made by Nature—The Bacterial Flagellar Motor

    PubMed Central

    Xue, Ruidong; Ma, Qi

    2015-01-01

    The bacterial flagellar motor (BFM) is a molecular complex ca. 45 nm in diameter that rotates the propeller that makes nearly all bacteria swim. The motor self‐assembles out of ca. 20 different proteins and can not only rotate at up to 50 000 rpm, but can also switch rotational direction in milliseconds and navigate its environment to maneuver, on average, towards regions of greater benefit. The BFM is a pinnacle of evolution that informs and inspires the design of novel nanotechnology in the new era of synthetic biology. PMID:27980978

  16. Nanoconfined catalytic Ångström-size motors.

    PubMed

    Colberg, Peter H; Kapral, Raymond

    2015-11-14

    Self-propelled chemically powered synthetic micron and nano-scale motors are being intensively studied because of the wide range of potential applications that exploit their directed motion. This paper considers even smaller Ångström-size synthetic motors. Such very small motors in bulk solution display effects arising from their self-propulsion. Recent experiments have shown that small-molecule catalysts and single enzyme molecules exhibit properties that have been attributed to their chemical activity. Molecular dynamics is used to investigate the properties of very small Ångström-size synthetic chemically powered sphere-dimer motors in a simple atomic-like solvent confined between walls separated by distances of tens of nanometers. Evidence for strong structural ordering of the motors between the walls, which reflects the finite size of solvent molecules and depends on solvent depletion forces, is provided. Dynamical properties, such as average motor velocity, orientational relaxation, and mean square displacement, are anisotropic and depend on the distance from the walls. This research provides information needed for potential applications that use molecular-scale motors in the complex confined geometries encountered in biology and the laboratory.

  17. Nanoconfined catalytic Ångström-size motors

    SciTech Connect

    Colberg, Peter H. Kapral, Raymond

    2015-11-14

    Self-propelled chemically powered synthetic micron and nano-scale motors are being intensively studied because of the wide range of potential applications that exploit their directed motion. This paper considers even smaller Ångström-size synthetic motors. Such very small motors in bulk solution display effects arising from their self-propulsion. Recent experiments have shown that small-molecule catalysts and single enzyme molecules exhibit properties that have been attributed to their chemical activity. Molecular dynamics is used to investigate the properties of very small Ångström-size synthetic chemically powered sphere-dimer motors in a simple atomic-like solvent confined between walls separated by distances of tens of nanometers. Evidence for strong structural ordering of the motors between the walls, which reflects the finite size of solvent molecules and depends on solvent depletion forces, is provided. Dynamical properties, such as average motor velocity, orientational relaxation, and mean square displacement, are anisotropic and depend on the distance from the walls. This research provides information needed for potential applications that use molecular-scale motors in the complex confined geometries encountered in biology and the laboratory.

  18. Nanoconfined catalytic Ångström-size motors

    NASA Astrophysics Data System (ADS)

    Colberg, Peter H.; Kapral, Raymond

    2015-11-01

    Self-propelled chemically powered synthetic micron and nano-scale motors are being intensively studied because of the wide range of potential applications that exploit their directed motion. This paper considers even smaller Ångström-size synthetic motors. Such very small motors in bulk solution display effects arising from their self-propulsion. Recent experiments have shown that small-molecule catalysts and single enzyme molecules exhibit properties that have been attributed to their chemical activity. Molecular dynamics is used to investigate the properties of very small Ångström-size synthetic chemically powered sphere-dimer motors in a simple atomic-like solvent confined between walls separated by distances of tens of nanometers. Evidence for strong structural ordering of the motors between the walls, which reflects the finite size of solvent molecules and depends on solvent depletion forces, is provided. Dynamical properties, such as average motor velocity, orientational relaxation, and mean square displacement, are anisotropic and depend on the distance from the walls. This research provides information needed for potential applications that use molecular-scale motors in the complex confined geometries encountered in biology and the laboratory.

  19. B13+: Photodriven Molecular Wankel Engine

    SciTech Connect

    Zhang, Jin; Sergeeva, Alina P.; Sparta, Manuel; Alexandrova, Anastassia N.

    2012-07-09

    Synthetic molecular motors that are capable of delivering controlled movement upon energy input are one of the key building blocks in nanomachinery. The major energy sources of molecular motors are from chemical reactions, photon beams, or electric current, which are converted into mechanical forces through the excitation of the electronic states of the molecule. The energy scale of the electronic excitation is normally two orders of magnitude larger than the molecular vibrational frequencies. To reduce the heat dissipation and increase the energy utilization efficiency, a motor running purely on the electronic ground-state (GS) potential energy surfaces is highly desirable.

  20. Cargo Transport by Two Coupled Myosin Va Motors on Actin Filaments and Bundles.

    PubMed

    Ali, M Yusuf; Vilfan, Andrej; Trybus, Kathleen M; Warshaw, David M

    2016-11-15

    Myosin Va (myoVa) is a processive, actin-based molecular motor essential for intracellular cargo transport. When a cargo is transported by an ensemble of myoVa motors, each motor faces significant physical barriers and directional challenges created by the complex actin cytoskeleton, a network of actin filaments and actin bundles. The principles that govern the interaction of multiple motors attached to the same cargo are still poorly understood. To understand the mechanical interactions between multiple motors, we developed a simple in vitro model in which two individual myoVa motors labeled with different-colored Qdots are linked via a third Qdot that acts as a cargo. The velocity of this two-motor complex was reduced by 27% as compared to a single motor, whereas run length was increased by only 37%, much less than expected from multimotor transport models. Therefore, at low ATP, which allowed us to identify individual motor steps, we investigated the intermotor dynamics within the two-motor complex. The randomness of stepping leads to a buildup of tension in the linkage between motors-which in turn slows down the leading motor-and increases the frequency of backward steps and the detachment rate. We establish a direct relationship between the velocity reduction and the distribution of intermotor distances. The analysis of run lengths and dwell times for the two-motor complex, which has only one motor engaged with the actin track, reveals that half of the runs are terminated by almost simultaneous detachment of both motors. This finding challenges the assumptions of conventional multimotor models based on consecutive motor detachment. Similar, but even more drastic, results were observed with two-motor complexes on actin bundles, which showed a run length that was even shorter than that of a single motor.

  1. A New Type of Motor: Pneumatic Step Motor

    PubMed Central

    Stoianovici, Dan; Patriciu, Alexandru; Petrisor, Doru; Mazilu, Dumitru; Kavoussi, Louis

    2011-01-01

    This paper presents a new type of pneumatic motor, a pneumatic step motor (PneuStep). Directional rotary motion of discrete displacement is achieved by sequentially pressurizing the three ports of the motor. Pulsed pressure waves are generated by a remote pneumatic distributor. The motor assembly includes a motor, gearhead, and incremental position encoder in a compact, central bore construction. A special electronic driver is used to control the new motor with electric stepper indexers and standard motion control cards. The motor accepts open-loop step operation as well as closed-loop control with position feedback from the enclosed sensor. A special control feature is implemented to adapt classic control algorithms to the new motor, and is experimentally validated. The speed performance of the motor degrades with the length of the pneumatic hoses between the distributor and motor. Experimental results are presented to reveal this behavior and set the expectation level. Nevertheless, the stepper achieves easily controllable precise motion unlike other pneumatic motors. The motor was designed to be compatible with magnetic resonance medical imaging equipment, for actuating an image-guided intervention robot, for medical applications. For this reason, the motors were entirely made of nonmagnetic and dielectric materials such as plastics, ceramics, and rubbers. Encoding was performed with fiber optics, so that the motors are electricity free, exclusively using pressure and light. PneuStep is readily applicable to other pneumatic or hydraulic precision-motion applications. PMID:21528106

  2. Robust transport by multiple motors with nonlinear force-velocity relations and stochastic load sharing

    NASA Astrophysics Data System (ADS)

    Kunwar, Ambarish; Mogilner, Alexander

    2010-03-01

    Transport by processive molecular motors plays an important role in many cell biological phenomena. In many cases, motors work together to transport cargos in the cell, so it is important to understand the mechanics of the multiple motors. Based on earlier modeling efforts, here we study effects of nonlinear force-velocity relations and stochastic load sharing on multiple motor transport. We find that when two or three motors transport the cargo, then the nonlinear and stochastic effects compensate so that the mechanical properties of the transport are robust. Similarly, the transport is insensitive to compliance of the cargo-motor links. Furthermore, the rate of movement against moderate loads is not improved by increasing the small number of motors. When the motor number is greater than 4, correlations between the motors become negligible, and the earlier analytical mean-field theory of the multiple motor transport holds. We predict that the effective diffusion of the cargo driven by the multiple motors under load increases by an order of magnitude compared to that for the single motor. Finally, our simulations predict that the stochastic effects are responsible for a significant dispersion of velocities generated by the 'tug-of-war' of the multiple opposing motors.

  3. Robust transport by multiple motors with nonlinear force-velocity relations and stochastic load sharing.

    PubMed

    Kunwar, Ambarish; Mogilner, Alexander

    2010-02-10

    Transport by processive molecular motors plays an important role in many cell biological phenomena. In many cases, motors work together to transport cargos in the cell, so it is important to understand the mechanics of the multiple motors. Based on earlier modeling efforts, here we study effects of nonlinear force-velocity relations and stochastic load sharing on multiple motor transport. We find that when two or three motors transport the cargo, then the nonlinear and stochastic effects compensate so that the mechanical properties of the transport are robust. Similarly, the transport is insensitive to compliance of the cargo-motor links. Furthermore, the rate of movement against moderate loads is not improved by increasing the small number of motors. When the motor number is greater than 4, correlations between the motors become negligible, and the earlier analytical mean-field theory of the multiple motor transport holds. We predict that the effective diffusion of the cargo driven by the multiple motors under load increases by an order of magnitude compared to that for the single motor. Finally, our simulations predict that the stochastic effects are responsible for a significant dispersion of velocities generated by the 'tug-of-war' of the multiple opposing motors.

  4. Robust transport by multiple motors with nonlinear force–velocity relations and stochastic load sharing

    PubMed Central

    Kunwar, Ambarish; Mogilner, Alexander

    2010-01-01

    Transport by processive molecular motors plays an important role in many cell biological phenomena. In many cases, motors work together to transport cargos in the cell, so it is important to understand the mechanics of the multiple motors. Based on earlier modeling efforts, here we study effects of nonlinear force–velocity relations and stochastic load sharing on multiple motor transport. We find that when two or three motors transport the cargo, then the nonlinear and stochastic effects compensate so that the mechanical properties of the transport are robust. Similarly, the transport is insensitive to compliance of the cargo-motor links. Furthermore, the rate of movement against moderate loads is not improved by increasing the small number of motors. When the motor number is greater than 4, correlations between the motors become negligible, and the earlier analytical mean-field theory of the multiple motor transport holds. We predict that the effective diffusion of the cargo driven by the multiple motors under load increases by an order of magnitude compared to that for the single motor. Finally, our simulations predict that the stochastic effects are responsible for a significant dispersion of velocities generated by the ‘tug-of-war’ of the multiple opposing motors. PMID:20147778

  5. Transcriptional regulation of mouse hypoglossal motor neuron somatotopic map formation.

    PubMed

    Chen, Xin; Wang, Jae Woong; Salin-Cantegrel, Adele; Dali, Rola; Stifani, Stefano

    2016-11-01

    Somatic motor neurons in the hypoglossal nucleus innervate tongue muscles controlling vital functions such as chewing, swallowing and respiration. Formation of functional hypoglossal nerve circuits depends on the establishment of precise hypoglossal motor neuron maps correlating with specific tongue muscle innervations. Little is known about the molecular mechanisms controlling mammalian hypoglossal motor neuron topographic map formation. Here we show that combinatorial expression of transcription factors Runx1, SCIP and FoxP1 defines separate mouse hypoglossal motor neuron groups with different topological, neurotransmitter and calcium-buffering phenotypes. Runx1 and SCIP are coexpressed in ventromedial hypoglossal motor neurons involved in control of tongue protrusion whereas FoxP1 is expressed in dorsomedial motor neurons associated with tongue retraction. Establishment of separate hypoglossal motor neuron maps depends in part on Runx1-mediated suppression of ventrolateral and dorsomedial motor neuron phenotypes and regulation of FoxP1 expression pattern. These findings suggest that combinatorial actions of Runx1, SCIP and FoxP1 are important for mouse hypoglossal nucleus somatotopic map formation.

  6. Dualities in the analysis of phage DNA packaging motors

    PubMed Central

    Serwer, Philip; Jiang, Wen

    2012-01-01

    The DNA packaging motors of double-stranded DNA phages are models for analysis of all multi-molecular motors and for analysis of several fundamental aspects of biology, including early evolution, relationship of in vivo to in vitro biochemistry and targets for anti-virals. Work on phage DNA packaging motors both has produced and is producing dualities in the interpretation of data obtained by use of both traditional techniques and the more recently developed procedures of single-molecule analysis. The dualities include (1) reductive vs. accretive evolution, (2) rotation vs. stasis of sub-assemblies of the motor, (3) thermal ratcheting vs. power stroking in generating force, (4) complete motor vs. spark plug role for the packaging ATPase, (5) use of previously isolated vs. new intermediates for analysis of the intermediate states of the motor and (6) a motor with one cycle vs. a motor with two cycles. We provide background for these dualities, some of which are under-emphasized in the literature. We suggest directions for future research. PMID:23532204

  7. Role of motor unit structure in defining function

    NASA Technical Reports Server (NTRS)

    Monti, R. J.; Roy, R. R.; Edgerton, V. R.

    2001-01-01

    Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge. Copyright 2001 John Wiley & Sons, Inc.

  8. A structural pathway for activation of the kinesin motor ATPase

    PubMed Central

    Yun, Mikyung; Zhang, Xiaohua; Park, Cheon-Gil; Park, Hee-Won; Endow, Sharyn A.

    2001-01-01

    Molecular motors move along actin or microtubules by rapidly hydrolyzing ATP and undergoing changes in filament-binding affinity with steps of the nucleotide hydrolysis cycle. It is generally accepted that motor binding to its filament greatly increases the rate of ATP hydrolysis, but the structural changes in the motor associated with ATPase activation are not known. To identify the conformational changes underlying motor movement on its filament, we solved the crystal structures of three kinesin mutants that decouple nucleotide and microtubule binding by the motor, and block microtubule-activated, but not basal, ATPase activity. Conformational changes in the structures include a disordered loop and helices in the switch I region and a visible switch II loop, which is disordered in wild-type structures. Switch I moved closer to the bound nucleotide in two mutant structures, perturbing water-mediated interactions with the Mg2+. This could weaken Mg2+ binding and accelerate ADP release to activate the motor ATPase. The structural changes we observe define a signaling pathway within the motor for ATPase activation that is likely to be essential for motor movement on microtubules. PMID:11387196

  9. A catalytic oligomeric motor that walks along a filament track

    SciTech Connect

    Huang, Mu-Jie Kapral, Raymond

    2015-06-28

    Most biological motors in the cell execute chemically powered conformational changes as they walk on biopolymer filaments in order to carry out directed transport functions. Synthetic motors that operate in a similar manner are being studied since they have the potential to perform similar tasks in a variety of applications. In this paper, a synthetic nanomotor that moves along a filament track, without invoking motor conformational changes, is constructed and its properties are studied in detail. The motor is an oligomer comprising three linked beads with specific binding properties. The filament track is a stiff polymer chain, also described by a linear chain of linked coarse-grained molecular groups modeled as beads. Reactions on the filament that are catalyzed by a motor bead and use fuel in the environment, in conjunction within the binding affinities of the motor beads to the filament beads, lead to directed motion. The system operates out of equilibrium due to the state of the filament and supply of fuel. The motor, filament, and surrounding medium are all described at microscopic level that permits a full analysis of the motor motion. A stochastic model that captures the main trends seen in the simulations is also presented. The results of this study point to some of the key features that could be used to construct nanomotors that undergo biased walks powered by chemical reactions on filaments.

  10. An autonomous chemically fuelled small-molecule motor

    NASA Astrophysics Data System (ADS)

    Wilson, Miriam R.; Solà, Jordi; Carlone, Armando; Goldup, Stephen M.; Lebrasseur, Nathalie; Leigh, David A.

    2016-06-01

    Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.

  11. An autonomous chemically fuelled small-molecule motor.

    PubMed

    Wilson, Miriam R; Solà, Jordi; Carlone, Armando; Goldup, Stephen M; Lebrasseur, Nathalie; Leigh, David A

    2016-06-09

    Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.

  12. Magnetostrictive direct drive motor

    NASA Technical Reports Server (NTRS)

    Naik, Dipak; Dehoff, P. H.

    1991-01-01

    Highly magnetostrictive materials such as Tb.3Dy.7Fe2, commercially known as TERFENOL-D, have been used to date in a variety of devices such as high power actuators and linear motors. The larger magnetostriction available in twinned single crystal TERFENOL-D, approx. 2000 ppm at moderate magnetic field strengths, makes possible a new generation of magnetomechanical devices. NASA researchers are studying the potential of this material as the basis for a direct microstepping rotary motor with torque densities on the order of industrial hydraulics and five times greater than that of the most efficient, high power electric motors. Such a motor would be a micro-radian stepper, capable of precision movements and self-braking in the power-off state. Innovative mechanical engineering techniques are juxtaposed on proper magnetic circuit design to reduce losses in structural flexures, inertias, thermal expansions, eddy currents, and magneto-mechanical coupling, thus optimizing motor performance and efficiency. Mathematical models are presented, including magnetic, structural, and both linear and nonlinear dynamic calculations and simulations. In addition, test results on prototypes are presented.

  13. Molecular-beam gas-sampling system

    NASA Technical Reports Server (NTRS)

    Young, W. S.; Knuth, E. L.

    1972-01-01

    A molecular beam mass spectrometer system for rocket motor combustion chamber sampling is described. The history of the sampling system is reviewed. The problems associated with rocket motor combustion chamber sampling are reported. Several design equations are presented. The results of the experiments include the effects of cooling water flow rates, the optimum separation gap between the end plate and sampling nozzle, and preliminary data on compositions in a rocket motor combustion chamber.

  14. Magnetostrictive direct drive motors

    NASA Technical Reports Server (NTRS)

    Naik, Dipak; Dehoff, P. H.

    1990-01-01

    Developing magnetostrictive direct drive research motors to power robot joints is discussed. These type motors are expected to produce extraordinary torque density, to be able to perform microradian incremental steps and to be self-braking and safe with the power off. Several types of motor designs have been attempted using magnetostrictive materials. One of the candidate approaches (the magnetostrictive roller drive) is described. The method in which the design will function is described as is the reason why this approach is inherently superior to the other approaches. Following this, the design will be modelled and its expected performance predicted. This particular candidate design is currently undergoing detailed engineering with prototype construction and testing scheduled for mid 1991.

  15. Micromachine Wedge Stepping Motor

    SciTech Connect

    Allen, J.J.; Schriner, H.K.

    1998-11-04

    A wedge stepping motor, which will index a mechanism, has been designed and fabricated in the surface rnicromachine SUMMiT process. This device has demonstrated the ability to index one gear tooth at a time with speeds up to 205 teeth/see. The wedge stepper motor has the following features, whi:h will be useful in a number of applications. o The ability to precisely position mechanical components. . Simple pulse signals can be used for operation. o Only 2 drive signals are requixed for operation. o Torque and precision capabilities increase with device size . The device to be indexed is restrained at all times by the wedge shaped tooth that is used for actuation. This paper will discuss the theory of operation and desi=m of the wedge stepping motor. The fabrication and testing of I he device will also be presented.

  16. Bent shaft motor

    DOEpatents

    Benavides, Gilbert L.

    1998-01-01

    A nonelectromagnetic motor comprising a base, a bent shaft which is rotable relative to the base wherein the bent shaft comprises a straight portion aligned with a main axis and an offset portion that is offset with respect to the main axis; and a drive means for driving the offset portion of the bent shaft along a generally circular path in a plane perpendicular to the main axis to rotate the bent shaft. The bent shaft and drive means for driving the bent shaft can be selected from piezoelectric, magnetostrictive, rheological and shape memory alloys. The drive means of the nonelectromagnetic motor can additionally comprise a shell which shell surrounds and houses the bent shaft and precesses or gyrates which in turn causes the bent drive shaft to rotate. The nonelectromagnetic motor does not rely on friction for the application of torque upon a rotor.

  17. Bent shaft motor

    DOEpatents

    Benavides, G.L.

    1998-05-05

    A nonelectromagnetic motor comprising a base, a bent shaft which is rotatable relative to the base wherein the bent shaft comprises a straight portion aligned with a main axis and an offset portion that is offset with respect to the main axis; and a drive means for driving the offset portion of the bent shaft along a generally circular path in a plane perpendicular to the main axis to rotate the bent shaft. The bent shaft and drive means for driving the bent shaft can be selected from piezoelectric, magnetostrictive, rheological and shape memory alloys. The drive means of the nonelectromagnetic motor can additionally comprise a shell which shell surrounds and houses the bent shaft and precesses or gyrates which in turn causes the bent drive shaft to rotate. The nonelectromagnetic motor does not rely on friction for the application of torque upon a rotor. 11 figs.

  18. The functional alterations associated with motor imagery training: a comparison between motor execution and motor imagery of sequential finger tapping

    NASA Astrophysics Data System (ADS)

    Zhang, Hang; Yao, Li; Long, Zhiying

    2011-03-01

    Motor imagery training, as an effective strategy, has been more and more applied to mental disorders rehabilitation and motor skill learning. Studies on the neural mechanism underlying motor imagery have suggested that such effectiveness may be related to the functional congruence between motor execution and motor imagery. However, as compared to the studies on motor imagery, the studies on motor imagery training are much fewer. The functional alterations associated with motor imagery training and the effectiveness of motor imagery training on motor performance improvement still needs further investigation. Using fMRI, we employed a sequential finger tapping paradigm to explore the functional alterations associated with motor imagery training in both motor execution and motor imagery task. We hypothesized through 14 consecutive days motor imagery training, the motor performance could be improved and the functional congruence between motor execution and motor imagery would be sustained form pre-training phase to post-training phase. Our results confirmed the effectiveness of motor imagery training in improving motor performance and demonstrated in both pre and post-training phases, motor imagery and motor execution consistently sustained the congruence in functional neuroanatomy, including SMA (supplementary motor cortex), PMA (premotor area); M1( primary motor cortex) and cerebellum. Moreover, for both execution and imagery tasks, a similar functional alteration was observed in fusiform through motor imagery training. These findings provided an insight into the effectiveness of motor imagery training and suggested its potential therapeutic value in motor rehabilitation.

  19. ac bidirectional motor controller

    NASA Technical Reports Server (NTRS)

    Schreiner, K.

    1988-01-01

    Test data are presented and the design of a high-efficiency motor/generator controller at NASA-Lewis for use with the Space Station power system testbed is described. The bidirectional motor driver is a 20 kHz to variable frequency three-phase ac converter that operates from the high-frequency ac bus being designed for the Space Station. A zero-voltage-switching pulse-density-modulation technique is used in the converter to shape the low-frequency output waveform.

  20. Motor current signature analysis method for diagnosing motor operated devices

    DOEpatents

    Haynes, Howard D.; Eissenberg, David M.

    1990-01-01

    A motor current noise signature analysis method and apparatus for remotely monitoring the operating characteristics of an electric motor-operated device such as a motor-operated valve. Frequency domain signal analysis techniques are applied to a conditioned motor current signal to distinctly identify various operating parameters of the motor driven device from the motor current signature. The signature may be recorded and compared with subsequent signatures to detect operating abnormalities and degradation of the device. This diagnostic method does not require special equipment to be installed on the motor-operated device, and the current sensing may be performed at remote control locations, e.g., where the motor-operated devices are used in accessible or hostile environments.

  1. 46 CFR 169.684 - Overcurrent protection for motors and motor branch circuits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Overcurrent protection for motors and motor branch... motors and motor branch circuits. (a) Except as provided in paragraph (d) of this section, each motor... motor that is responsive to motor current or to both motor current and temperature may be used. (b)...

  2. 46 CFR 169.684 - Overcurrent protection for motors and motor branch circuits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Overcurrent protection for motors and motor branch... motors and motor branch circuits. (a) Except as provided in paragraph (d) of this section, each motor... motor that is responsive to motor current or to both motor current and temperature may be used. (b)...

  3. Magnetically Coupled Adjustable Speed Motor Drives - Motor Tip Sheet #13

    SciTech Connect

    2008-07-01

    Alternating current electric motors rotate at a nearly constant speed that is determined by motor design and line frequency. Energy savings of 50% or more may be available when fixed speed systems are modified to allow the motor speed to match variable load requirements of a centrifugal fan or pump.

  4. Method for assessing motor insulation on operating motors

    DOEpatents

    Kueck, J.D.; Otaduy, P.J.

    1997-03-18

    A method for monitoring the condition of electrical-motor-driven devices is disclosed. The method is achieved by monitoring electrical variables associated with the functioning of an operating motor, applying these electrical variables to a three phase equivalent circuit and determining non-symmetrical faults in the operating motor based upon symmetrical components analysis techniques. 15 figs.

  5. Method for assessing motor insulation on operating motors

    DOEpatents

    Kueck, John D.; Otaduy, Pedro J.

    1997-01-01

    A method for monitoring the condition of electrical-motor-driven devices. The method is achieved by monitoring electrical variables associated with the functioning of an operating motor, applying these electrical variables to a three phase equivalent circuit and determining non-symmetrical faults in the operating motor based upon symmetrical components analysis techniques.

  6. 'TRPing' synaptic ribbon function in the rat pineal gland: neuroendocrine regulation involves the capsaicin receptor TRPV1.

    PubMed

    Reuss, Stefan; Disque-Kaiser, Ursula; Binzen, Uta; Greffrath, Wolfgang; Peschke, Elmar

    2010-01-01

    Synaptic ribbons (SRs) are presynaptic structures thought to regulate and facilitate multivesicular release. In the pineal gland, they display a circadian rhythm with higher levels at night paralleling melatonin synthesis. To gain more insight into the processes involved and the possible functions of these structures, a series of experiments were conducted in rodents. We studied the regional distribution of a molecular marker of pineal SRs, the kinesin motor KIF3A in the gland. Respective immunoreactivity was abundant in central regions of the gland where sympathetic fibers were less dense, and vice versa, revealing that intercellular communication between adjacent pinealocytes is enhanced under low sympathetic influence. KIF3A was found to be colocalized to the transient receptor potential channel of the vanilloid receptor family, subtype 1 (TRPV1). The TRPV1 agonist capsaicin increased melatonin secretion from perifused pineals in a dose-dependent manner that was blocked by the competitive TRPV1 antagonist capsazepine. No change in free intracellular calcium was observed in response to TRPV1 ligands applied to pinealocytes responding to norepinephrine, bradykinin and/or depolarization. These data clearly indicate that TRPV1 actively regulates pineal gland function.

  7. Electric motor model repair specifications

    SciTech Connect

    1995-08-01

    These model repair specifications list the minimum requirements for repair and overhaul of polyphase AC squireel cage induction motors. All power ranges, voltages, and speeds of squirrel cage motors are covered.

  8. Reciprocating Linear Electric Motor

    NASA Technical Reports Server (NTRS)

    Goldowsky, M. P.

    1984-01-01

    Features include structural simplicity and good force/displacement characteristics. Reciprocating motor has simple, rugged construction, relatively low reciprocating weight, improved power delivery, and improved force control. Wear reduced by use of magnetic bearings. Intended to provide drivers for long-lived Stirling-cycle cryogenic refrigerators, concept has less exotic applications, such as fuel pumps.

  9. Perceptual-Motor Dysfunction.

    ERIC Educational Resources Information Center

    Pyfer, Jean L.

    Discussed are theoretical and treatment aspects of perceptual motor dysfunction and rehabilitation in 4- to 12-year-old academically failing children involved in a 3-year investigation at the University of Kansas. The program is said to stress increasing the amount of stimulation received by sensory receptors of the vestibular, reflex, and haptic…

  10. Thiokol Solid Rocket Motors

    NASA Technical Reports Server (NTRS)

    Graves, S. R.

    2000-01-01

    This paper presents viewgraphs on thiokol solid rocket motors. The topics include: 1) Communications; 2) Military and government intelligence; 3) Positioning satellites; 4) Remote sensing; 5) Space burial; 6) Science; 7) Space manufacturing; 8) Advertising; 9) Space rescue space debris management; 10) Space tourism; 11) Space settlements; 12) Hazardous waste disposal; 13) Extraterrestrial resources; 14) Fast package delivery; and 15) Space utilities.

  11. The St. Louis Motor

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    2011-01-01

    The St. Louis Motor, invented in 1909, is unique among physics apparatus for being named for a geographical place rather than a physicist. The sturdy little device (Fig. 1) has never been out of production. Any older school or physics department that has not done a catastrophic housecleaning in the last 20 years will certainly have a small flock…

  12. Velocity Fluctuations in Kinesin-1 Gliding Motility Assays Originate in Motor Attachment Geometry Variations.

    PubMed

    Palacci, Henri; Idan, Ofer; Armstrong, Megan J; Agarwal, Ashutosh; Nitta, Takahiro; Hess, Henry

    2016-08-09

    Motor proteins such as myosin and kinesin play a major role in cellular cargo transport, muscle contraction, cell division, and engineered nanodevices. Quantifying the collective behavior of coupled motors is critical to our understanding of these systems. An excellent model system is the gliding motility assay, where hundreds of surface-adhered motors propel one cytoskeletal filament such as an actin filament or a microtubule. The filament motion can be observed using fluorescence microscopy, revealing fluctuations in gliding velocity. These velocity fluctuations have been previously quantified by a motional diffusion coefficient, which Sekimoto and Tawada explained as arising from the addition and removal of motors from the linear array of motors propelling the filament as it advances, assuming that different motors are not equally efficient in their force generation. A computational model of kinesin head diffusion and binding to the microtubule allowed us to quantify the heterogeneity of motor efficiency arising from the combination of anharmonic tail stiffness and varying attachment geometries assuming random motor locations on the surface and an absence of coordination between motors. Knowledge of the heterogeneity allows the calculation of the proportionality constant between the motional diffusion coefficient and the motor density. The calculated value (0.3) is within a standard error of our measurements of the motional diffusion coefficient on surfaces with varying motor densities calibrated by landing rate experiments. This allowed us to quantify the loss in efficiency of coupled molecular motors arising from heterogeneity in the attachment geometry.

  13. Self-organized pattern formation in motor-microtubule mixtures

    NASA Astrophysics Data System (ADS)

    Sankararaman, Sumithra; Menon, Gautam I.; Sunil Kumar, P. B.

    2004-09-01

    We model the stable self-organized patterns obtained in the nonequilibrium steady states of mixtures of molecular motors and microtubules. In experiments [Nédélec , Nature (London) 389, 305 (1997); Surrey , Science 292, 1167 (2001)] performed in a quasi-two-dimensional geometry, microtubules are oriented by complexes of motor proteins. This interaction yields a variety of patterns, including arrangements of asters, vortices, and disordered configurations. We model this system via a two-dimensional vector field describing the local coarse-grained microtubule orientation and two scalar density fields associated to molecular motors. These scalar fields describe motors which either attach to and move along microtubules or diffuse freely within the solvent. Transitions between single aster, spiral, and vortex states are obtained as a consequence of confinement, as parameters in our model are varied. For systems in which the effects of confinement can be neglected, we present a map of nonequilibrium steady states, which includes arrangements of asters and vortices separately as well as aster-vortex mixtures and fully disordered states. We calculate the steady state distribution of bound and free motors in aster and vortex configurations of microtubules and compare these to our simulation results, providing qualitative arguments for the stability of different patterns in various regimes of parameter space. We study the role of crowding or “saturation” effects on the density profiles of motors in asters, discussing the role of such effects in stabilizing single asters. We also comment on the implications of our results for experiments.

  14. [The neuronal level of motor activity: determination of motor cortex excitability by TMS].

    PubMed

    Eichhammer, Peter; Langguth, Berthold; Müller, Jürgen; Hajak, Göran

    2005-04-01

    Transcranial magnetic stimulation as mapping method offers the possibility to measure aspects of motor cortex excitability painlessly and non-invasively. Using this neurophysiological tool, new insights into the effects of central-acting drugs are possible. Particularly striking seems to be the potential of this approach to gain new insights into neurobiological processes associated with neuropsychiatric diseases like schizophrenia or major depression. In combination with genetic aspects, TMS is able to bridge the gap between molecular research and clinical approach.

  15. Rotary torque produced by proton motive force in FoF{sub 1} motor

    SciTech Connect

    Zhang Yinghao; Wang Jun; Cui Yuanbo; Yue Jiachang . E-mail: yuejc@sun5.ibp.ac.cn; Fang Xiaohong

    2005-05-27

    We have attempted direct observation of the light-driven rotation of a FoF{sub 1}-ATP motor. The FoF{sub 1}-ATP motor was co-reconstituted by the deletion-{delta} subunit of FoF{sub 1}-ATP synthase with bacteriorhodopsins (BRs) into a liposome. The BR converts radiation energy into electrochemical gradient of proton to drive the FoF{sub 1}-ATP motor. Therefore, the light-driven rotation of FoF{sub 1}-ATP motor has been directly observed by a fluorescence microscopy using a fluorescent actin filament connected to {beta}-subunit as a marker of its orientation. The rotational torque value of the Fo motor was calculated as 27.93 {+-} 1.88 pN nm. The ATP motor is expected to be a promising rotary molecular motor in the development of nanodevices.

  16. Tandem motors reduce well costs

    SciTech Connect

    Hooper, M.; Daigle, C.; Crowe, R.

    1995-10-01

    The new generation of tandem mud motors that recently appeared on the drilling scene is significantly affecting drilling efficiency worldwide. These motors provide drillers with increased horsepower at the bit, higher torque, and faster rates of penetration (ROP). With advanced engineering and more durable materials, motor life is being extended, thereby increasing the time between bit trips and reducing drilling costs. This article reviews the performance, design, and operation of these motors.

  17. Motor Vehicle Theft. Special Report.

    ERIC Educational Resources Information Center

    Harlow, Caroline Wolf

    Thirteen years of data from the National Crime Survey were analyzed to examine the characteristics of motor vehicle theft, to identify trends during the past 13 years, and to determine who are most likely to be victims of motor vehicle theft. All motor vehicle thefts reported to the National Crime Survey from 1973 through 1985 were examined.…

  18. Speed control for synchronous motors

    NASA Technical Reports Server (NTRS)

    Packard, H.; Schott, J.

    1981-01-01

    Feedback circuit controls fluctuations in speed of synchronous ac motor. Voltage proportional to phase angle is developed by phase detector, rectified, amplified, compared to threshold, and reapplied positively or negatively to motor excitation circuit. Speed control reduces wow and flutter of audio turntables and tape recorders, and enhances hunting in gyroscope motors.

  19. Experiments with a DC Motor

    ERIC Educational Resources Information Center

    Kraftmakher, Yaakov

    2010-01-01

    Experiments with an electric motor provide good opportunity to demonstrate some basic laws of electricity and magnetism. The aim of the experiments with a low-power dc motor is to show how the motor approaches its steady rotation and how its torque, mechanical power and efficiency depend on the rotation velocity. The tight relationship between the…

  20. Brushless direct-current motors

    NASA Technical Reports Server (NTRS)

    Bahm, E. J.

    1970-01-01

    Survey results are presented on the use of unconventional motor windings and switching sequences to optimize performance of brushless dc motors. A motor was built, each coil terminal having a separate, accessible lead. With the shaft and all electronics excluded, length and outside diameter measured 1.25 and 0.75 in., respectively.

  1. Motor Education: Educational Development Programs.

    ERIC Educational Resources Information Center

    Tansley, A. E.

    This booklet presents educational programs and activities focusing on motor skills for 5- to 9-year-old children and older children with learning problems. The premise of the activities is that the acquisition of motor skills is essential to basic learning. The role of language as a mediator and controller of motor development is emphasized. The…

  2. Multiple stage miniature stepping motor

    DOEpatents

    Niven, William A.; Shikany, S. David; Shira, Michael L.

    1981-01-01

    A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

  3. Sufficient conditions for the additivity of stall forces generated by multiple filaments or motors

    NASA Astrophysics Data System (ADS)

    Bameta, Tripti; Das, Dipjyoti; Das, Dibyendu; Padinhateeri, Ranjith; Inamdar, Mandar M.

    2017-02-01

    Molecular motors and cytoskeletal filaments work collectively most of the time under opposing forces. This opposing force may be due to cargo carried by motors or resistance coming from the cell membrane pressing against the cytoskeletal filaments. Some recent studies have shown that the collective maximum force (stall force) generated by multiple cytoskeletal filaments or molecular motors may not always be just a simple sum of the stall forces of the individual filaments or motors. To understand this excess or deficit in the collective force, we study a broad class of models of both cytoskeletal filaments and molecular motors. We argue that the stall force generated by a group of filaments or motors is additive, that is, the stall force of N number of filaments (motors) is N times the stall force of one filament (motor), when the system is reversible at stall. Conversely, we show that this additive property typically does not hold true when the system is irreversible at stall. We thus present a novel and unified understanding of the existing models exhibiting such non-addivity, and generalise our arguments by developing new models that demonstrate this phenomena. We also propose a quantity similar to thermodynamic efficiency to easily predict this deviation from stall-force additivity for filament and motor collectives.

  4. Motor sequence learning and motor adaptation in primary cervical dystonia.

    PubMed

    Katschnig-Winter, Petra; Schwingenschuh, Petra; Davare, Marco; Sadnicka, Anna; Schmidt, Reinhold; Rothwell, John C; Bhatia, Kailash P; Edwards, Mark J

    2014-06-01

    Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning and motor adaptation in patients with primary cervical dystonia. We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor from a central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Patients with cervical dystonia had a significantly higher peak velocity than controls. Baseline performance with random target presentation was otherwise normal. Patients and controls had similar levels of motor sequence learning and motor adaptation. Our patients had significantly higher peak velocity compared to controls, with similar movement times, implying a different performance strategy. The preservation of motor sequence learning in cervical dystonia patients contrasts with the previously observed deficit seen in patients with DYT1 gene mutations, supporting the hypothesis of differing pathophysiology in different forms of primary dystonia. Normal motor adaptation is an interesting finding. With our paradigm we did not find evidence that the previously documented cerebellar abnormalities in cervical dystonia have a behavioral correlate, and thus could be compensatory or reflect "contamination" rather than being directly pathological.

  5. Processive cytoskeletal motors studied with single-molecule fluorescence techniques.

    PubMed

    Belyy, Vladislav; Yildiz, Ahmet

    2014-10-01

    Processive cytoskeletal motors from the myosin, kinesin, and dynein families walk on actin filaments and microtubules to drive cellular transport and organization in eukaryotic cells. These remarkable molecular machines are able to take hundreds of successive steps at speeds of up to several microns per second, allowing them to effectively move vesicles and organelles throughout the cytoplasm. Here, we focus on single-molecule fluorescence techniques and discuss their wide-ranging applications to the field of cytoskeletal motor research. We cover both traditional fluorescence and sub-diffraction imaging of motors, providing examples of how fluorescence data can be used to measure biophysical parameters of motors such as coordination, stepping mechanism, gating, and processivity. We also outline some remaining challenges in the field and suggest future directions.

  6. A synthetic DNA motor that transports nanoparticles along carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Cha, Tae-Gon; Pan, Jing; Chen, Haorong; Salgado, Janette; Li, Xiang; Mao, Chengde; Choi, Jong Hyun

    2014-01-01

    Intracellular protein motors have evolved to perform specific tasks critical to the function of cells such as intracellular trafficking and cell division. Kinesin and dynein motors, for example, transport cargoes in living cells by walking along microtubules powered by adenosine triphosphate hydrolysis. These motors can make discrete 8 nm centre-of-mass steps and can travel over 1 µm by changing their conformations during the course of adenosine triphosphate binding, hydrolysis and product release. Inspired by such biological machines, synthetic analogues have been developed including self-assembled DNA walkers that can make stepwise movements on RNA/DNA substrates or can function as programmable assembly lines. Here, we show that motors based on RNA-cleaving DNA enzymes can transport nanoparticle cargoes--CdS nanocrystals in this case--along single-walled carbon nanotubes. Our motors extract chemical energy from RNA molecules decorated on the nanotubes and use that energy to fuel autonomous, processive walking through a series of conformational changes along the one-dimensional track. The walking is controllable and adapts to changes in the local environment, which allows us to remotely direct `go' and `stop' actions. The translocation of individual motors can be visualized in real time using the visible fluorescence of the cargo nanoparticle and the near-infared emission of the carbon-nanotube track. We observed unidirectional movements of the molecular motors over 3 µm with a translocation velocity on the order of 1 nm min-1 under our experimental conditions.

  7. Variation in motor output and motor performance in a centrally generated motor pattern.

    PubMed

    Wenning, Angela; Norris, Brian J; Doloc-Mihu, Anca; Calabrese, Ronald L

    2014-07-01

    Central pattern generators (CPGs) produce motor patterns that ultimately drive motor outputs. We studied how functional motor performance is achieved, specifically, whether the variation seen in motor patterns is reflected in motor performance and whether fictive motor patterns differ from those in vivo. We used the leech heartbeat system in which a bilaterally symmetrical CPG coordinates segmental heart motor neurons and two segmented heart tubes into two mutually exclusive coordination modes: rear-to-front peristaltic on one side and nearly synchronous on the other, with regular side-to-side switches. We assessed individual variability of the motor pattern and the beat pattern in vivo. To quantify the beat pattern we imaged intact adults. To quantify the phase relations between motor neurons and heart constrictions we recorded extracellularly from two heart motor neurons and movement from the corresponding heart segments in minimally dissected leeches. Variation in the motor pattern was reflected in motor performance only in the peristaltic mode, where larger intersegmental phase differences in the motor neurons resulted in larger phase differences between heart constrictions. Fictive motor patterns differed from those in vivo only in the synchronous mode, where intersegmental phase differences in vivo had a larger front-to-rear bias and were more constrained. Additionally, load-influenced constriction timing might explain the amplification of the phase differences between heart segments in the peristaltic mode and the higher variability in motor output due to body shape assumed in this soft-bodied animal. The motor pattern determines the beat pattern, peristaltic or synchronous, but heart mechanics influence the phase relations achieved.

  8. Motor technology for mining applications advances

    SciTech Connect

    Fiscor, S.

    2009-08-15

    AC motors are steadily replacing DC motors in mining and mineral processing equipment, requiring less maintenance. The permanent magnet rotor, or the synchronous motor, has enabled Blador to introduce a line of cooling tower motors. Synchronous motors are soon likely to take over from the induction motor. 1 photo.

  9. Big Savings from Smart Motors

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Chesebrough-Pond's operates 32 plants across the nation and in those plants are more than 10,000 electric motors. In an effort to cut down on waste of electrical power used by these motors, Chesebrough organized a Corporate Advanced Technology Group to devise ways of improving productivity and cut manufacturing costs. Chesebrough used NASA's Marshall Space Flight Center's Power Factor Controller technology as a departure point for development of their own computerized motor controller that enables motors to operate at maximum efficiency regardless of the motor's applications or operating condition.

  10. Single molecule thermodynamics in biological motors.

    PubMed

    Taniguchi, Yuichi; Karagiannis, Peter; Nishiyama, Masayoshi; Ishii, Yoshiharu; Yanagida, Toshio

    2007-04-01

    Biological molecular machines use thermal activation energy to carry out various functions. The process of thermal activation has the stochastic nature of output events that can be described according to the laws of thermodynamics. Recently developed single molecule detection techniques have allowed each distinct enzymatic event of single biological machines to be characterized providing clues to the underlying thermodynamics. In this study, the thermodynamic properties in the stepping movement of a biological molecular motor have been examined. A single molecule detection technique was used to measure the stepping movements at various loads and temperatures and a range of thermodynamic parameters associated with the production of each forward and backward step including free energy, enthalpy, entropy and characteristic distance were obtained. The results show that an asymmetry in entropy is a primary factor that controls the direction in which the motor will step. The investigation on single molecule thermodynamics has the potential to reveal dynamic properties underlying the mechanisms of how biological molecular machines work.

  11. Prospective errors determine motor learning

    PubMed Central

    Takiyama, Ken; Hirashima, Masaya; Nozaki, Daichi

    2015-01-01

    Diverse features of motor learning have been reported by numerous studies, but no single theoretical framework concurrently accounts for these features. Here, we propose a model for motor learning to explain these features in a unified way by extending a motor primitive framework. The model assumes that the recruitment pattern of motor primitives is determined by the predicted movement error of an upcoming movement (prospective error). To validate this idea, we perform a behavioural experiment to examine the model’s novel prediction: after experiencing an environment in which the movement error is more easily predictable, subsequent motor learning should become faster. The experimental results support our prediction, suggesting that the prospective error might be encoded in the motor primitives. Furthermore, we demonstrate that this model has a strong explanatory power to reproduce a wide variety of motor-learning-related phenomena that have been separately explained by different computational models. PMID:25635628

  12. Magnetostrictive direct drive motors

    NASA Technical Reports Server (NTRS)

    Naik, Dipak; Dehoff, P. H.

    1992-01-01

    A new rare earth alloy, Terfenol-D, combines low frequency operation and extremely high energy density with high magnetostriction. Its material properties make it suitable as a drive element for actuators requiring high output torque. The high strains, the high forces and the high controllability of Terfenol alloys provide a powerful and challenging basis for new ways to generate motion in actuators. Two prototypes of motors using Terfenol-D rods were developed at NASA Goddard. The basic principles of operation are provided of the motor along with other relevant details. A conceptual design of a torque limiting safety clutch/brake under development is illustrated. Also, preliminary design drawings of a linear actuator using Terfenol-D is shown.

  13. Ironless armature torque motor

    NASA Technical Reports Server (NTRS)

    Fisher, R. L.

    1972-01-01

    Four iron-less armature torque motors, four Hall device position sensor assemblies, and two test fixtures were fabricated. The design approach utilized samarium cobalt permanent magnets, a large airgap, and a three-phase winding in a stationary ironless armature. Hall devices were employed to sense rotor position. An ironless armature torque motor having an outer diameter of 4.25 inches was developed to produce a torque constant of 65 ounce-inches per ampere with a resistance of 20.5 ohms. The total weight, including structural elements, was 1.58 pounds. Test results indicated that all specifications were met except for generated voltage waveform. It is recommended that investigations be made concerning the generated voltage waveform to determine if it may be improved.

  14. Advanced Motor Drives Studies

    NASA Technical Reports Server (NTRS)

    Ehsani, M.; Tchamdjou, A.

    1997-01-01

    This report presents an evaluation of advanced motor drive systems as a replacement for the hydrazine fueled APU units. The replacement technology must meet several requirements which are particular to the space applications and the Orbiter in general. Some of these requirements are high efficiency, small size, high power density. In the first part of the study several motors are compared, based on their characteristics and in light of the Orbiter requirements. The best candidate, the brushless DC is chosen because of its particularly good performance with regards to efficiency. Several power electronics drive technologies including the conventional three-phase hard switched and several soft-switched inverters are then presented. In the last part of the study, a soft-switched inverter is analyzed and compared to its conventional hard-switched counterpart. Optimal efficiency is a basic requirement for space applications and the soft-switched technology represents an unavoidable trend for the future.

  15. The St. Louis Motor

    NASA Astrophysics Data System (ADS)

    Greenslade, Thomas B.

    2011-10-01

    The St. Louis Motor, invented in 1909, is unique among physics apparatus for being named for a geographical place rather than a physicist. The sturdy little device (Fig. 1) has never been out of production. Any older school or physics department that has not done a catastrophic housecleaning in the last 20 years will certainly have a small flock of them in the back room.

  16. Motor neurone disease.

    PubMed

    2016-03-23

    Essential facts Motor neurone disease describes a group of related diseases, affecting the neurones in the brain and spinal cord. Progressive, incurable and life-limiting, MND is rare, with about 1,100 people developing it each year in the UK and up to 5,000 people affected at any one time. One third of people will die within a year of diagnosis and more than half within two years. About 5% to 10% are alive at ten years.

  17. EPDM rocket motor insulation

    NASA Technical Reports Server (NTRS)

    Guillot, David G. (Inventor); Harvey, Albert R. (Inventor)

    2004-01-01

    A novel and improved EPDM formulation for a solid propellant rocket motor is described wherein hexadiene EPDM monomer components are replaced by alkylidene norbornene components, and, with appropriate adjustment of curing and other additives, functionally required rheological and physical characteristics are achieved with the desired compatibility with any one of a plurality of solid filler materials, e.g., powder silica, carbon fibers or aramid fibers, and with appropriate adhesion and extended storage or shelf-life characteristics.

  18. Libert-E Motor

    ERIC Educational Resources Information Center

    Sieloff, Susan F.; Kinnunen, Raymond; Chevarley, Joseph

    2011-01-01

    Kei Yun Wong has big dreams. She has been entrusted with the United States launch of Libert-E Motor, a new line of Chinese-manufactured electric scooters. With only $750,000 of her original budget of $3 million left, she needs to make sure that the launch succeeds, as it represents the initial step in her desire to create the first Chinese global…

  19. EPDM rocket motor insulation

    NASA Technical Reports Server (NTRS)

    Guillot, David G. (Inventor); Harvey, Albert R. (Inventor)

    2008-01-01

    A novel and improved EPDM formulation for a solid propellant rocket motor is described wherein hexadiene EPDM monomer components are replaced by alkylidene norbornene components, and, with appropriate adjustment of curing and other additives, functionally required rheological and physical characteristics are achieved with the desired compatibility with any one of a plurality of solid filler materials, e.g., powder silica, carbon fibers or aramid fibers, and with appropriate adhesion and extended storage or shelf-life characteristics.

  20. EPDM rocket motor insulation

    NASA Technical Reports Server (NTRS)

    Guillot, David G. (Inventor); Harvey, Albert R. (Inventor)

    2003-01-01

    A novel and improved EPDM formulation for a solid propellant rocket motor is described wherein hexadiene EPDM monomer components are replaced by alkylidene norbornene components and with appropriate adjustment of curing and other additives functionally-required rheological and physical characteristics are achieved with the desired compatibility with any one of a plurality of solid filler materials, e.g. powder silica, carbon fibers or aramid fibers, and with appropriate adhesion and extended storage or shelf life characteristics.

  1. Dyspraxia, motor function and visual-motor integration in autism.

    PubMed

    Miller, M; Chukoskie, L; Zinni, M; Townsend, J; Trauner, D

    2014-08-01

    This project assessed dyspraxia in high-functioning school aged children with autism with a focus on Ideational Praxis. We examined the association of specific underlying motor function including eye movement with ideational dyspraxia (sequences of skilled movements) as well as the possible role of visual-motor integration in dyspraxia. We found that compared to IQ-, sex- and age-matched typically developing children, the children with autism performed significantly worse on: Ideational and Buccofacial praxis; a broad range of motor tests, including measures of simple motor skill, timing and accuracy of saccadic eye movements and motor coordination; and tests of visual-motor integration. Impairments in individual children with autism were heterogeneous in nature, although when we examined the praxis data as a function of a qualitative measure representing motor timing, we found that children with poor motor timing performed worse on all praxis categories and had slower and less accurate eye movements while those with regular timing performed as well as typical children on those same tasks. Our data provide evidence that both motor function and visual-motor integration contribute to dyspraxia. We suggest that dyspraxia in autism involves cerebellar mechanisms of movement control and the integration of these mechanisms with cortical networks implicated in praxis.

  2. Motor Fuel Excise Taxes

    SciTech Connect

    2015-09-01

    A new report from the National Renewable Energy Laboratory (NREL) explores the role of alternative fuels and energy efficient vehicles in motor fuel taxes. Throughout the United States, it is common practice for federal, state, and local governments to tax motor fuels on a per gallon basis to fund construction and maintenance of our transportation infrastructure. In recent years, however, expenses have outpaced revenues creating substantial funding shortfalls that have required supplemental funding sources. While rising infrastructure costs and the decreasing purchasing power of the gas tax are significant factors contributing to the shortfall, the increased use of alternative fuels and more stringent fuel economy standards are also exacerbating revenue shortfalls. The current dynamic places vehicle efficiency and petroleum use reduction polices at direct odds with policies promoting robust transportation infrastructure. Understanding the energy, transportation, and environmental tradeoffs of motor fuel tax policies can be complicated, but recent experiences at the state level are helping policymakers align their energy and environmental priorities with highway funding requirements.

  3. Motor actuated vacuum door

    NASA Astrophysics Data System (ADS)

    Hanagud, A. V.

    1986-10-01

    Doors that allow scientific instruments to record and retrieve the observed data are often required to be designed and installed as a part of sounding rocket hardware. The motor-actuated vacuum door was designed to maintain a medium vacuum of the order of 0.0001 torr or better while closed, and to provide an opening 15 inches long x 8.5 inches wide while open for cameras to image Halley's comet. When the electric motor receives the instruction to open the door through the payload battery, timer, and relay circuit, the first operation is to unlock the door. After unlatching, the torque transmitted by the motor to the main shaft through the links opens the door. A microswitch actuator, which rides on the linear motion conversion mechanism, is adjusted to trip the limit switch at the end of the travel. The process is repeated in the reverse order to close the door. 'O' rings are designed to maintain the seal. Door mechanisms similar to the one described have flown on Aerobee 17.018 and Black Brant 27.047 payloads.

  4. Five-site model for a motor protein walking on a bead-spring substrate

    NASA Astrophysics Data System (ADS)

    Paudyal, Nabina; Adeli Koudehi, Maral; Luettmer-Strathmann, Jutta

    2014-03-01

    Motor proteins play an important role in many biological processes. For example, kinesin molecules are responsible for the transport of vesicles in nerve cells and their malfunction has been linked to neurodegenerative diseases. Motor proteins are also responsible for the unique mechanical properties of active matter. To study non-equilibrium aspects of motor-substrate systems, biological chain molecules interacting with motor proteins have been investigated in single-chain pulling experiments. Unfortunately, the complexity of motor proteins and their environment makes it difficult to model the detailed dynamics of molecular motors over long time scales. In this work, we develop a simple coarse-grained model for a motor protein on a bead-spring substrate under tension. In our model, different pair potentials describe interactions between substrate and motor, motor components and substrate components. The movement of motor proteins entails ATP hydrolysis, which is modeled in terms of mechano-chemical states that couple positional and chemical degrees of freedom. The goal of this work is to simulate cargo transport in confined geometries and to investigate the mechanical response of a single chain interacting with motor proteins.

  5. Coordinated Switching of Bacterial Flagellar Motors: Evidence for Direct Motor-Motor Coupling?

    NASA Astrophysics Data System (ADS)

    Hu, Bo; Tu, Yuhai

    2013-04-01

    The swimming of Escherichia coli is powered by its multiple flagellar motors. Each motor spins either clockwise or counterclockwise, under the control of an intracellular regulator, CheY-P. There can be two mechanisms (extrinsic and intrinsic) to coordinate the switching of bacterial motors. The extrinsic one arises from the fact that different motors in the same cell sense a common input (CheY-P) which fluctuates near the motors’ response threshold. An alternative, intrinsic mechanism is direct motor-motor coupling which makes synchronized switching energetically favorable. Here, we develop simple models for both mechanisms and uncover their different hallmarks. A quantitative comparison to the recent experiments suggests that the direct coupling mechanism may be accountable for the observed sharp correlation between motors in a single Escherichia coli. Possible origins of this coupling (e.g., hydrodynamic interaction) are discussed.

  6. How Biophysics May Help Us Understand the Flagellar Motor of Bacteria Which Cause Infections.

    PubMed

    Baker, Matthew A B

    2016-01-01

    Motor proteins are molecules which convert chemical energy to mechanical work and are responsible for motility across all levels: for transport within a cell, for the motion of an individual cell in its surroundings, and for movement in multicellular aggregates, such as muscles. The bacterial flagellar motor is one of the canonical examples of a molecular complex made from several motor proteins, which self-assembles on demand and provides the locomotive force for bacteria. This locomotion provides a key aspect of bacteria's prevalence. Here, we outline the biophysics behind the assembly, the energetics, the switching and the rotation of this remarkable nanoscale electric motor that is Nature's first wheel.

  7. Wind motor applications for transportation

    SciTech Connect

    Lysenko, G.P.; Grigoriev, B.V.; Karpin, K.B.

    1996-12-31

    Motion equation for a vehicle equipped with a wind motor allows, taking into account the drag coefficients, to determine the optimal wind drag velocity in the wind motor`s plane, and hence, obtain all the necessary data for the wind wheel blades geometrical parameters definition. This optimal drag velocity significantly differs from the flow drag velocity which determines the maximum wind motor power. Solution of the motion equation with low drag coefficients indicates that the vehicle speed against the wind may be twice as the wind speed. One of possible transportation wind motor applications is its use on various ships. A ship with such a wind motor may be substantially easier to steer, and if certain devices are available, may proceed in autonomous control mode. Besides, it is capable of moving within narrow fairways. The cruise speed of a sailing boat and wind-motored ship were compared provided that the wind velocity direction changes along a harmonic law with regard to the motion direction. Mean dimensionless speed of the wind-motored ship appears to be by 20--25% higher than that of a sailing boat. There was analyzed a possibility of using the wind motors on planet rovers in Mars or Venus atmospheric conditions. A Mars rover power and motor system has been assessed for the power level of 3 kW.

  8. Comparison of capabilities of reluctance synchronous motor and induction motor

    NASA Astrophysics Data System (ADS)

    Štumberger, Gorazd; Hadžiselimović, Miralem; Štumberger, Bojan; Miljavec, Damijan; Dolinar, Drago; Zagradišnik, Ivan

    2006-09-01

    This paper compares the capabilities of a reluctance synchronous motor (RSM) with those of an induction motor (IM). An RSM and IM were designed and made, with the same rated power and speed. They differ only in the rotor portion while their stators, housings and cooling systems are identical. The capabilities of both motors in a variable speed drive are evaluated by comparison of the results obtained by magnetically nonlinear models and by measurements.

  9. Messengers, motors and mysteries: sorting of eukaryotic mRNAs by cytoskeletal transport.

    PubMed

    Bullock, Simon L

    2011-10-01

    It has become increasingly apparent in recent years that the subcellular localization of specific mRNAs is a prevalent method for spatially controlling gene expression. In most cases, targeting of mRNAs is mediated by transport along cytoskeletal filaments by molecular motors. However, the means by which specific messages are recognized and linked to the motors are poorly understood. Here, I will provide an overview of recent progress in elucidating the molecular mechanisms and principles of mRNA transport, including several studies highlighting the co-operation of different motors during the localization process. Important outstanding questions will also be highlighted.

  10. Chopped molecular beam multiplexing system

    NASA Technical Reports Server (NTRS)

    Adams, Billy R. (Inventor)

    1986-01-01

    The integration of a chopped molecular beam mass spectrometer with a time multiplexing system is described. The chopping of the molecular beam is synchronized with the time intervals by a phase detector and a synchronous motor. Arithmetic means are generated for phase shifting the chopper with respect to the multiplexer. A four channel amplifier provides the capacity to independently vary the baseline and amplitude in each channel of the multiplexing system.

  11. Force per cross-sectional area from molecules to muscles: a general property of biological motors.

    PubMed

    Rospars, Jean-Pierre; Meyer-Vernet, Nicole

    2016-07-01

    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area-classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 10(19) mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as M(α) with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result.

  12. Force per cross-sectional area from molecules to muscles: a general property of biological motors

    PubMed Central

    Meyer-Vernet, Nicole

    2016-01-01

    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area—classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 1019 mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as Mα with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result. PMID:27493785

  13. Sensory change following motor learning.

    PubMed

    Mattar, Andrew A G; Nasir, Sazzad M; Darainy, Mohammad; Ostry, David J

    2011-01-01

    Here we describe two studies linking perceptual change with motor learning. In the first, we document persistent changes in somatosensory perception that occur following force field learning. Subjects learned to control a robotic device that applied forces to the hand during arm movements. This led to a change in the sensed position of the limb that lasted at least 24 h. Control experiments revealed that the sensory change depended on motor learning. In the second study, we describe changes in the perception of speech sounds that occur following speech motor learning. Subjects adapted control of speech movements to compensate for loads applied to the jaw by a robot. Perception of speech sounds was measured before and after motor learning. Adapted subjects showed a consistent shift in perception. In contrast, no consistent shift was seen in control subjects and subjects that did not adapt to the load. These studies suggest that motor learning changes both sensory and motor function.

  14. Sport expert's motor imagery: functional imaging of professional motor skills and simple motor skills.

    PubMed

    Wei, Gaoxia; Luo, Jing

    2010-06-23

    Numerous studies provide evidence that motor skill acquisition is associated with dynamic changes in cortical and subcortical regions. Athletes are a professional population who are engaged in extensive motor training for long periods. However, the neural substrates of extreme level motor performance have not been clarified. We used kinesthetic imagery task to induce the mental representation of sport expert's extraordinary performance in view of the shared substrates of executing movement and motor imagery. For the first time, we compared, through functional magnetic resonance imaging (fMRI), the pattern of cerebral activations in 12 professional divers and 12 normal people without extensive training, during imagery of professional skills and imagery of simple motor skills. The sport experts showed significant activation in the parahippocampus during imagery of professional skills relative to the novices, which might reflect the representation adapted to experience-related motor tasks. No significant difference was found between experts and novices when they imagined simple motor skills. These results indicated the experts might utilize their kinesthetic imagery more efficiently than novices, but only for the activity in which they had expertise. The sport experts also demonstrated more focused activation patterns in prefrontal areas in both of imagery tasks, which may be relevant to higher order of motor control during motor imagery. Moreover, this study suggested that the brains of sport experts could be regarded as the ideal subjects to explore the relationship between cerebral plasticity and learning of complex motor skills.

  15. Dissociation of motor maturation.

    PubMed

    DiMario, Francis J

    2003-06-01

    We prospectively acquired clinical data regarding the presentation, evaluation, and developmental progress of all patients identified with dissociated motor maturation to define their clinical outcomes. Children (N = 8) referred for evaluation of suspected cerebral palsy because of delayed sitting or walking and identified to have dissociated motor maturation were followed with serial clinical examination. All displayed the characteristic "sitting on air" posture while held in vertical suspension and had otherwise normal developmental assessments. This posture is composed of the hips held in flexion and abduction with the knees extended and feet plantar or dorsiflexed. Three children were initially evaluated at 10 months of age owing to absence of sitting and five other children were evaluated at a mean of 14 months (range 12-19 months) owing to inability to stand. Follow-up evaluations were conducted over a mean of 10.5 months (range 5-34 months). Five children were born prematurely at 34 to 36 weeks gestation. Denver Developmental Screening Test and general and neurologic examinations were normal except to note hypotonia in six children and the "sitting on air" posture in all of the children. Four children have older siblings or parents who "walked late" (after 15 months). On average, the children attained sitting by 8 months (range 7-10 months). One child did not crawl prior to independent walking, two children scooted rather than crawled, and five children crawled at an average of 13.5 months (range 10-16 months). All children cruised by a mean of 18 months (range 16-21.5 months) and attained independent walking by 20.1 months (range 18-25 months). Neuroimaging and serum creatine kinase enzyme testing were normal in two children who were tested. These eight children conform to the syndrome of dissociated motor maturation. The "sitting on air" posture serves as a diagnostic sign and anticipated excellent prognosis, but follow-up is required to ensure a normal

  16. Electric motor analysis at Dofasco

    SciTech Connect

    Brooks, D.; Morgan, V.A.; Nicholas, J.R. Jr.

    1997-03-01

    Initiatives adopted by Dofasco to enhance electric motor reliability and availability include: Enhancement of the electrical repair shop testing and repair capabilities; More stringent standards for motor repair service vendors; Application of predictive technologies to motors in service within manufacturing units; Training of personnel in electrical predictive condition monitoring and analysis methods; and Periodic audit and comparison of central support and operating unit predictive technology application and integration. The basis for the initiative is discussed together with illustrative case histories.

  17. Torque-Summing Brushless Motor

    NASA Technical Reports Server (NTRS)

    Vaidya, J. G.

    1986-01-01

    Torque channels function cooperatively but electrically independent for reliability. Brushless, electronically-commutated dc motor sums electromagnetic torques on four channels and applies them to single shaft. Motor operates with any combination of channels and continues if one or more of channels fail electrically. Motor employs single stator and rotor and mechanically simple; however, each of channels electrically isolated from other so that failure of one does not adversely affect others.

  18. How Actin Initiates the Motor Activity of Myosin

    PubMed Central

    Llinas, Paola; Isabet, Tatiana; Song, Lin; Ropars, Virginie; Zong, Bin; Benisty, Hannah; Sirigu, Serena; Morris, Carl; Kikuti, Carlos; Safer, Dan; Sweeney, H. Lee; Houdusse, Anne

    2015-01-01

    SUMMARY Fundamental to cellular processes are directional movements driven by molecular motors. A common theme for these and other molecular machines driven by ATP is that controlled release of hydrolysis products is essential to use the chemical energy efficiently. Mechanochemical transduction by myosin motors on actin is coupled to unknown structural changes that result in the sequential release of inorganic phosphate (Pi) and MgADP. We present here a myosin structure possessing an actin-binding interface and a tunnel (back door) that creates an escape route for Pi with a minimal rotation of the myosin lever arm that drives movements. We propose that this state represents the beginning of the powerstroke on actin, and that Pi translocation from the nucleotide pocket triggered by actin binding initiates myosin force generation. This elucidates how actin initiates force generation and movement, and may represent a strategy common to many molecular machines. PMID:25936506

  19. How actin initiates the motor activity of Myosin.

    PubMed

    Llinas, Paola; Isabet, Tatiana; Song, Lin; Ropars, Virginie; Zong, Bin; Benisty, Hannah; Sirigu, Serena; Morris, Carl; Kikuti, Carlos; Safer, Dan; Sweeney, H Lee; Houdusse, Anne

    2015-05-26

    Fundamental to cellular processes are directional movements driven by molecular motors. A common theme for these and other molecular machines driven by ATP is that controlled release of hydrolysis products is essential for using the chemical energy efficiently. Mechanochemical transduction by myosin motors on actin is coupled to unknown structural changes that result in the sequential release of inorganic phosphate (Pi) and MgADP. We present here a myosin structure possessing an actin-binding interface and a tunnel (back door) that creates an escape route for Pi with a minimal rotation of the myosin lever arm that drives movements. We propose that this state represents the beginning of the powerstroke on actin and that Pi translocation from the nucleotide pocket triggered by actin binding initiates myosin force generation. This elucidates how actin initiates force generation and movement and may represent a strategy common to many molecular machines.

  20. Motor timing under microgravity.

    PubMed

    Semjen, A; Leone, G; Lipshits, M

    1998-01-01

    Five participants were tested on their ability to produce accurate and regular inter-response intervals in the 350 to 530 ms time range. Three of them were members of the French-Russian CASSIOPEE 96 spaceflight mission, and the other two were control subjects tested on the ground. During spaceflight, the target inter-response intervals were increasingly undershot and the timing became more variable (less regular). The increase in the timing variability was mostly attributable to the internal timekeeping processes rather than those involved in motor execution. The results are discussed with reference to the physiological mechanisms possibly underlying the timing of fast serial movements.

  1. Model Studies of the Dynamics of Bacterial Flagellar Motors

    SciTech Connect

    Bai, F; Lo, C; Berry, R; Xing, J

    2009-03-19

    The Bacterial Flagellar Motor is a rotary molecular machine that rotates the helical filaments which propel swimming bacteria. Extensive experimental and theoretical studies exist on the structure, assembly, energy input, power generation and switching mechanism of the motor. In our previous paper, we explained the general physics underneath the observed torque-speed curves with a simple two-state Fokker-Planck model. Here we further analyze this model. In this paper we show (1) the model predicts that the two components of the ion motive force can affect the motor dynamics differently, in agreement with the latest experiment by Lo et al.; (2) with explicit consideration of the stator spring, the model also explains the lack of dependence of the zero-load speed on stator number in the proton motor, recently observed by Yuan and Berg; (3) the model reproduces the stepping behavior of the motor even with the existence of the stator springs and predicts the dwelling time distribution. Predicted stepping behavior of motors with two stators is discussed, and we suggest future experimental verification.

  2. Concentration dependent red shift: qualitative and quantitative investigation of motor oils by synchronous fluorescence scan.

    PubMed

    Patra, D; Mishra, A K

    2001-01-05

    Synchronous fluorescence scan (SFS) has been described as a successful technique to characterize Motor oils like diesel, petrol, kerosene, 2T oil and Mobil. The concentration dependent investigation of Motor oils shows a red shift in lambda(SFS)(max). Using red shift of lambda(SFS)(max), a method has been developed to quantify Motor oil in the concentration range 5-100% v/v. The concentration dependent overall rate of energy transfer of Motor oil gives a unique behavioral change according to the oil type and SFS is a simpler spectroscopic method to qualitatively differentiate between heavy and light oil. The molecular interaction of polycyclic aromatic compounds (PACs) in fluorophoric mixtures like resonance energy transfer and self-quenching via solvent collision has been clearly explained by SFS method. Effect of solvent and external quencher molecule on Motor oils has also been studied. Nitrobenzene is found to be a selective quencher for PACs of Motor oils.

  3. A Stochastic Model for Microtubule Motors Describes the In Vivo Cytoplasmic Transport of Human Adenovirus

    PubMed Central

    Gazzola, Mattia; Burckhardt, Christoph J.; Bayati, Basil; Engelke, Martin; Greber, Urs F.; Koumoutsakos, Petros

    2009-01-01

    Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors. PMID:20041204

  4. A stochastic model for microtubule motors describes the in vivo cytoplasmic transport of human adenovirus.

    PubMed

    Gazzola, Mattia; Burckhardt, Christoph J; Bayati, Basil; Engelke, Martin; Greber, Urs F; Koumoutsakos, Petros

    2009-12-01

    Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors.

  5. Catch-slip bonds can be dispensable for motor force regulation during skeletal muscle contraction

    NASA Astrophysics Data System (ADS)

    Dong, Chenling; Chen, Bin

    2015-07-01

    It is intriguing how multiple molecular motors can perform coordinated and synchronous functions, which is essential in various cellular processes. Recent studies on skeletal muscle might have shed light on this issue, where rather precise motor force regulation was partly attributed to the specific stochastic features of a single attached myosin motor. Though attached motors can randomly detach from actin filaments either through an adenosine triphosphate (ATP) hydrolysis cycle or through "catch-slip bond" breaking, their respective contribution in motor force regulation has not been clarified. Here, through simulating a mechanical model of sarcomere with a coupled Monte Carlo method and finite element method, we find that the stochastic features of an ATP hydrolysis cycle can be sufficient while those of catch-slip bonds can be dispensable for motor force regulation.

  6. Modeling neck linker of kinesin motor movement with MRSR stochastic differential equation

    NASA Astrophysics Data System (ADS)

    Razali, Wan Qashishah Akmal Wan; Ramli, Siti Norafidah Mohd; Radiman, Shahidan

    2016-11-01

    Stochastic differential equation has a significant role in a range of biological areas including molecular motor like kinesin motor. Mean-reverting square root (MRSR) stochastic differential equation is commonly used in economics and finance areas. In this study, we use the MRSR stochastic differential equation to model neck linker motion of kinesin motor by considering the possibilities of rightward direction and occasionally in the leftward direction of kinesin movements. This neck linker docking model of kinesin motor incorporates the conformational change in the chemical kinetics and the tethered diffusion of the free head of kinesin motor. Here, we demonstrate this model by using Hookean spring method which referred to the stiffness model of neck linker. The motion of kinesin motor seems to be well described to move in unidirectional way with volatile behavior based on MRSR rather than common stochastic differential equation [DOI 10.1007/s11538-011-9697-6].

  7. Effect of fuel concentration on cargo transport by a team of Kinesin motors

    NASA Astrophysics Data System (ADS)

    Takshak, Anjneya; Mishra, Nirvantosh; Kulkarni, Aditi; Kunwar, Ambarish

    2017-02-01

    Eukaryotic cells employ specialized proteins called molecular motors for transporting organelles and vesicles from one location to another in a regulated and directed manner. These molecular motors often work collectively in a team while transporting cargos. Molecular motors use cytoplasmic ATP as fuel, which is hydrolyzed to generate mechanical force. While the effect of ATP concentration on cargo transport by single Kinesin motor function is well understood, it is still unexplored, both theoretically and experimentally, how ATP concentration would affect cargo transport by a team of Kinesin motors. For instance, how does fuel concentration affect the travel distances and travel velocities of cargo? How cooperativity of Kinesin motors engaged on a cargo is affected by ATP concentration? To answer these questions, here we develop mechano-chemical models of cargo transport by a team of Kinesin motors. To develop these models we use experimentally-constrained mechano-chemical model of a single Kinesin motor as well as earlier developed mean-field and stochastic models of load sharing for cargo transport. Thus, our new models for cargo transport by a team of Kinesin motors include fuel concentration explicitly, which was not considered in earlier models. We make several interesting predictions which can be tested experimentally. For instance, the travel distances of cargos are very large at limited ATP concentrations in spite of very small travel velocity. Velocities of cargos driven by multiple Kinesin have a Michaelis-Menten dependence on ATP concentration. Similarly, cooperativity among the engaged Kinesin motors on the cargo shows a Michaelis-Menten type dependence, which attains a maximum value near physiological ATP concentrations. Our new results can be potentially useful in controlling artificial nano-molecular shuttles precisely for targeted delivery in various nano-technological applications.

  8. Experimental demonstration of a single-molecule electric motor

    NASA Astrophysics Data System (ADS)

    Tierney, Heather L.; Murphy, Colin J.; Jewell, April D.; Baber, Ashleigh E.; Iski, Erin V.; Khodaverdian, Harout Y.; McGuire, Allister F.; Klebanov, Nikolai; Sykes, E. Charles H.

    2011-10-01

    For molecules to be used as components in molecular machines, methods that couple individual molecules to external energy sources and that selectively excite motion in a given direction are required. Significant progress has been made in the construction of molecular motors powered by light and by chemical reactions, but electrically driven motors have not yet been built, despite several theoretical proposals for such motors. Here we report that a butyl methyl sulphide molecule adsorbed on a copper surface can be operated as a single-molecule electric motor. Electrons from a scanning tunnelling microscope are used to drive the directional motion of the molecule in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. The direction and rate of the rotation are related to the chiralities of both the molecule and the tip of the microscope (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices.

  9. Experimental demonstration of a single-molecule electric motor.

    PubMed

    Tierney, Heather L; Murphy, Colin J; Jewell, April D; Baber, Ashleigh E; Iski, Erin V; Khodaverdian, Harout Y; McGuire, Allister F; Klebanov, Nikolai; Sykes, E Charles H

    2011-09-04

    For molecules to be used as components in molecular machines, methods that couple individual molecules to external energy sources and that selectively excite motion in a given direction are required. Significant progress has been made in the construction of molecular motors powered by light and by chemical reactions, but electrically driven motors have not yet been built, despite several theoretical proposals for such motors. Here we report that a butyl methyl sulphide molecule adsorbed on a copper surface can be operated as a single-molecule electric motor. Electrons from a scanning tunnelling microscope are used to drive the directional motion of the molecule in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. The direction and rate of the rotation are related to the chiralities of both the molecule and the tip of the microscope (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices.

  10. Cytoskeletal motor-driven active self-assembly in in vitro systems

    DOE PAGES

    Lam, A. T.; VanDelinder, V.; Kabir, A. M. R.; ...

    2015-11-11

    Molecular motor-driven self-assembly has been an active area of soft matter research for the past decade. Because molecular motors transform chemical energy into mechanical work, systems which employ molecular motors to drive self-assembly processes are able to overcome kinetic and thermodynamic limits on assembly time, size, complexity, and structure. Here, we review the progress in elucidating and demonstrating the rules and capabilities of motor-driven active self-assembly. Lastly, we focus on the types of structures created and the degree of control realized over these structures, and discuss the next steps necessary to achieve the full potential of this assembly mode whichmore » complements robotic manipulation and passive self-assembly.« less

  11. Cytoskeletal motor-driven active self-assembly in in vitro systems

    SciTech Connect

    Lam, A. T.; VanDelinder, V.; Hess, H.; Bachand, G. D.

    2015-11-11

    Molecular motor-driven self-assembly has been an active area of soft matter research for the past decade. Because molecular motors transform chemical energy into mechanical work, systems which employ molecular motors to drive self-assembly processes are able to overcome kinetic and thermodynamic limits on assembly time, size, complexity, and structure. Here, we review the progress in elucidating and demonstrating the rules and capabilities of motor-driven active self-assembly. Lastly, we focus on the types of structures created and the degree of control realized over these structures, and discuss the next steps necessary to achieve the full potential of this assembly mode which complements robotic manipulation and passive self-assembly.

  12. 76 FR 12792 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; General...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ... TRANSPORTATION National Highway Traffic Safety Administration Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; General Motors Corporation AGENCY: National Highway Traffic.... SUMMARY: This document grants in full the petition of General Motors Corporation's (GM) petition for...

  13. Motor power control circuit for ac induction motors

    NASA Technical Reports Server (NTRS)

    Nola, F. J. (Inventor)

    1983-01-01

    A motor power control of the type which functions by controlling the power factor wherein one of the parameters of power factor current on time is determined by the on time of a triac through which current is supplied to the motor. By means of a positive feedback circuit, a wider range of control is effected.

  14. 27. View, looking north, of motor house; the electric motor ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. View, looking north, of motor house; the electric motor and electric-powered winch are housed in section of building to the left. Photo by Jet Lowe, HAER, 1989. - Puget Sound Power & Light Company, White River Hydroelectric Project, 600 North River Avenue, Dieringer, Pierce County, WA

  15. Motor vehicle drivers' injuries in train-motor vehicle crashes.

    PubMed

    Zhao, Shanshan; Khattak, Aemal

    2015-01-01

    The objectives of this research were to: (1) identify a more suitable model for modeling injury severity of motor vehicle drivers involved in train-motor vehicle crashes at highway-rail grade crossings from among three commonly used injury severity models and (2) to investigate factors associated with injury severity levels of motor vehicle drivers involved in train-motor vehicle crashes at such crossings. The 2009-2013 highway-rail grade crossing crash data and the national highway-rail crossing inventory data were combined to produce the analysis dataset. Four-year (2009-2012) data were used for model estimation while 2013 data were used for model validation. The three injury severity levels-fatal, injury and no injury-were based on the reported intensity of motor-vehicle drivers' injuries at highway-rail grade crossings. The three injury severity models evaluated were: ordered probit, multinomial logit and random parameter logit. A comparison of the three models based on different criteria showed that the random parameter logit model and multinomial logit model were more suitable for injury severity analysis of motor vehicle drivers involved in crashes at highway-rail grade crossings. Some of the factors that increased the likelihood of more severe crashes included higher train and vehicle speeds, freight trains, older drivers, and female drivers. Where feasible, reducing train and motor vehicle speeds and nighttime lighting may help reduce injury severities of motor vehicle drivers.

  16. To What Extent Can Motor Imagery Replace Motor Execution While Learning a Fine Motor Skill?

    PubMed Central

    Sobierajewicz, Jagna; Szarkiewicz, Sylwia; Przekoracka-Krawczyk, Anna; Jaśkowski, Wojciech; van der Lubbe, Rob

    2016-01-01

    Motor imagery is generally thought to share common mechanisms with motor execution. In the present study, we examined to what extent learning a fine motor skill by motor imagery may substitute physical practice. Learning effects were assessed by manipulating the proportion of motor execution and motor imagery trials. Additionally, learning effects were compared between participants with an explicit motor imagery instruction and a control group. A Go/NoGo discrete sequence production (DSP) task was employed, wherein a five-stimulus sequence presented on each trial indicated the required sequence of finger movements after a Go signal. In the case of a NoGo signal, participants either had to imagine carrying out the response sequence (the motor imagery group), or the response sequence had to be withheld (the control group). Two practice days were followed by a final test day on which all sequences had to be executed. Learning effects were assessed by computing response times (RTs) and the percentages of correct responses (PCs). The electroencephalogram (EEG ) was additionally measured on this test day to examine whether motor preparation and the involvement of visual short term memory (VST M) depended on the amount of physical/mental practice. Accuracy data indicated strong learning effects. However, a substantial amount of physical practice was required to reach an optimal speed. EEG results suggest the involvement of VST M for sequences that had less or no physical practice in both groups. The absence of differences between the motor imagery and the control group underlines the possibility that motor preparation may actually resemble motor imagery. PMID:28154614

  17. To What Extent Can Motor Imagery Replace Motor Execution While Learning a Fine Motor Skill?

    PubMed

    Sobierajewicz, Jagna; Szarkiewicz, Sylwia; Przekoracka-Krawczyk, Anna; Jaśkowski, Wojciech; van der Lubbe, Rob

    2016-01-01

    Motor imagery is generally thought to share common mechanisms with motor execution. In the present study, we examined to what extent learning a fine motor skill by motor imagery may substitute physical practice. Learning effects were assessed by manipulating the proportion of motor execution and motor imagery trials. Additionally, learning effects were compared between participants with an explicit motor imagery instruction and a control group. A Go/NoGo discrete sequence production (DSP) task was employed, wherein a five-stimulus sequence presented on each trial indicated the required sequence of finger movements after a Go signal. In the case of a NoGo signal, participants either had to imagine carrying out the response sequence (the motor imagery group), or the response sequence had to be withheld (the control group). Two practice days were followed by a final test day on which all sequences had to be executed. Learning effects were assessed by computing response times (RTs) and the percentages of correct responses (PCs). The electroencephalogram (EEG ) was additionally measured on this test day to examine whether motor preparation and the involvement of visual short term memory (VST M) depended on the amount of physical/mental practice. Accuracy data indicated strong learning effects. However, a substantial amount of physical practice was required to reach an optimal speed. EEG results suggest the involvement of VST M for sequences that had less or no physical practice in both groups. The absence of differences between the motor imagery and the control group underlines the possibility that motor preparation may actually resemble motor imagery.

  18. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.

    PubMed

    Voon, Valerie; Brezing, Christina; Gallea, Cecile; Hallett, Mark

    2011-11-01

    Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation.

  19. Motor neurons and the generation of spinal motor neuron diversity

    PubMed Central

    Stifani, Nicolas

    2014-01-01

    Motor neurons (MNs) are neuronal cells located in the central nervous system (CNS) controlling a variety of downstream targets. This function infers the existence of MN subtypes matching the identity of the targets they innervate. To illustrate the mechanism involved in the generation of cellular diversity and the acquisition of specific identity, this review will focus on spinal MNs (SpMNs) that have been the core of significant work and discoveries during the last decades. SpMNs are responsible for the contraction of effector muscles in the periphery. Humans possess more than 500 different skeletal muscles capable to work in a precise time and space coordination to generate complex movements such as walking or grasping. To ensure such refined coordination, SpMNs must retain the identity of the muscle they innervate. Within the last two decades, scientists around the world have produced considerable efforts to elucidate several critical steps of SpMNs differentiation. During development, SpMNs emerge from dividing progenitor cells located in the medial portion of the ventral neural tube. MN identities are established by patterning cues working in cooperation with intrinsic sets of transcription factors. As the embryo develop, MNs further differentiate in a stepwise manner to form compact anatomical groups termed pools connecting to a unique muscle target. MN pools are not homogeneous and comprise subtypes according to the muscle fibers they innervate. This article aims to provide a global view of MN classification as well as an up-to-date review of the molecular mechanisms involved in the generation of SpMN diversity. Remaining conundrums will be discussed since a complete understanding of those mechanisms constitutes the foundation required for the elaboration of prospective MN regeneration therapies. PMID:25346659

  20. 46 CFR 111.70-3 - Motor controllers and motor-control centers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Motor controllers and motor-control centers. 111.70-3... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motor Circuits, Controllers, and Protection § 111.70-3 Motor controllers and motor-control centers. (a) General. The enclosure for each motor controller or...

  1. 46 CFR 111.70-3 - Motor controllers and motor-control centers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Motor controllers and motor-control centers. 111.70-3... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motor Circuits, Controllers, and Protection § 111.70-3 Motor controllers and motor-control centers. (a) General. The enclosure for each motor controller or...

  2. 46 CFR 111.70-3 - Motor controllers and motor-control centers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Motor controllers and motor-control centers. 111.70-3... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motor Circuits, Controllers, and Protection § 111.70-3 Motor controllers and motor-control centers. (a) General. The enclosure for each motor controller or...

  3. 46 CFR 111.70-3 - Motor controllers and motor-control centers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Motor controllers and motor-control centers. 111.70-3... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motor Circuits, Controllers, and Protection § 111.70-3 Motor controllers and motor-control centers. (a) General. The enclosure for each motor controller or...

  4. 46 CFR 111.70-3 - Motor controllers and motor-control centers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Motor controllers and motor-control centers. 111.70-3... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motor Circuits, Controllers, and Protection § 111.70-3 Motor controllers and motor-control centers. (a) General. The enclosure for each motor controller or...

  5. Advanced solid propellant motor insulation

    NASA Technical Reports Server (NTRS)

    Smith, P. L.; Russ, R. F.

    1972-01-01

    An advanced lightweight insulation system suitable for use in long duration, low pressure planetary orbiter-type motor applications was developed. Experiments included the screening of various filler and binder materials with optimization studies combining the best of each. Small scale test motor data were used to judge the degree of success.

  6. Computational approaches to motor control.

    PubMed

    Flash, T; Sejnowski, T J

    2001-12-01

    New concepts and computational models that integrate behavioral and neurophysiological observations have addressed several of the most fundamental long-standing problems in motor control. These problems include the selection of particular trajectories among the large number of possibilities, the solution of inverse kinematics and dynamics problems, motor adaptation and the learning of sequential behaviors.

  7. Motors and Bulbs in Series

    ERIC Educational Resources Information Center

    Whitaker, Robert J.

    2009-01-01

    One of Paul Hewitt's "Figuring Physics" that appeared in this journal dealt with the heating of a motor. This phenomenon can be demonstrated with a miniature motor and a bulb as part of a series of activities with "batteries and bulbs." Students examine the effect on the brightness of a single bulb when a second, identical bulb is placed in series…

  8. Motor Coordination and Executive Functions

    ERIC Educational Resources Information Center

    Michel, Eva

    2012-01-01

    Since Piaget, the view that motor and cognitive development are interrelated has gained wide acceptance. However, empirical research on this issue is still rare. Few studies show a correlation of performance in cognitive and motor tasks in typically developing children. More specifically, Diamond A. (2000) hypothesizes an involvement of executive…

  9. Conical Bearingless Motor/Generators

    NASA Technical Reports Server (NTRS)

    Kascak, P.; Jansen, R.; Dever, T.

    2008-01-01

    Motor/generators based on conical magnetic bearings have been invented as an improved alternative to prior such machines based, variously, on radial and/or axial magnetic bearings. Both the present and prior machines are members of the class of so-called bearingless or self bearing (in the sense of not containing mechanical bearings) rotary machines. Each motor/generator provides both a torque and force allowing it to either function as a motor and magnetic bearing or a generator and magnetic bearing concurrently. Because they are not subject to mechanical bearing wear, these machines have potentially long operational lives and can function without lubrication and over wide ranges of speed and temperature that include conditions under which lubricants would become depleted, degraded, or ineffective and mechanical bearings would fail. The figure shows three typical configurations of conical bearingless motor/generators. The main elements of each motor/generator are concentric rotor and stator portions having conically tapered surfaces facing each other across a gap. Because a conical motor/generator imposes both radial and axial magnetic forces, it acts, in effect, as a combination of an axial and a radial magnetic bearing. Therefore, only two conical motor/generators - one at each end of a rotor - are needed to effect complete magnetic leviation of the rotor, whereas previously, it was necessary to use a combination of an axial and a radial magnetic bearing at each end of the rotor to achieve complete magnetic levitation and a separate motor to provide torque.

  10. Power control for ac motor

    NASA Technical Reports Server (NTRS)

    Dabney, R. W. (Inventor)

    1984-01-01

    A motor controller employing a triac through which power is supplied to a motor is described. The open circuit voltage appearing across the triac controls the operation of a timing circuit. This timing circuit triggers on the triac at a time following turn off which varies inversely as a function of the amplitude of the open circuit voltage of the triac.

  11. Individualized Motor-Perceptual Study.

    ERIC Educational Resources Information Center

    Portland Public Schools, OR.

    This guide is being used in the Individualized Motor-Perceptual Study to determine whether working directly with kindergarten children to improve performance on motor-perceptual tasks will affect reading ability at the end of grades one, two, and three. The 5-year project involves six schools. In this guide, there are tips for teaching, suggested…

  12. Torque control for electric motors

    NASA Technical Reports Server (NTRS)

    Bernard, C. A.

    1980-01-01

    Method for adjusting electric-motor torque output to accomodate various loads utilizes phase-lock loop to control relay connected to starting circuit. As load is imposed, motor slows down, and phase lock is lost. Phase-lock signal triggers relay to power starting coil and generate additional torque. Once phase lock is recoverd, relay restores starting circuit to its normal operating mode.

  13. High efficiency motor rewind study

    NASA Astrophysics Data System (ADS)

    Wallace, A. K.; Spee, R.

    1991-02-01

    The objective of performing this work was to evaluate a new technology used for rewinding electric motors. Motor performance evaluation was conducted at the motor test facility at Oregon State University. The test program consisted of comparing new high efficiency motor technology and standard rewind technology with the Unity-Plus system. The Unity-Plus configuration exhibited reduced efficiency over the complete load range compared to the other motors. Appropriately sized capacitors connected to the terminals of the conventional induction motor produced the same power factor improvement as the Unity-Plus system. Torque production and torque pulsation were very similar for all systems. The Unity-Plus configuration drew lower starting currents but the duration of the starting transient was increased. Motor temperature rise was about the same for all systems. Noise levels were about the same in all systems. Although determination of time to failure was not undertaken, the expected lifetime of the Unit-Plus system is probably less due to higher capacitor stress and higher insulation stress. The investigation concludes that a conventional induction motor with terminal capacitors is the most acceptable way of obtaining good efficiency and power factor and the Unity-Plus system cannot be recommended on the basis of any of the evaluation criteria used in this study.

  14. Activities for a Perceptual Motor Program.

    ERIC Educational Resources Information Center

    Brinning, Dorothy; And Others

    Perceptual motor activities for physically handicapped children are presented in the areas of fine and gross motor skills. Also detailed are activities to develop body image, visual motor skills, and tactile and auditory perception. (JD)

  15. Industrial motor repair in the United States

    SciTech Connect

    Schueler, V.; Leistner, P.; Douglass, J.

    1994-09-01

    This report characterizes the motor repair industry in the United States; summarizes current motor repair and testing practice; and identifies barriers to energy motor repair practice and recommends strategies for overcoming those barriers.

  16. An interacting adiabatic quantum motor

    NASA Astrophysics Data System (ADS)

    Viola Kusminskiy, Silvia; Bruch, Anton; von Oppen, Felix

    We consider the effect of electron-electron interactions on the performance of an adiabatic quantum motor based on a Thouless pump operating in reverse. We model such a device by electrons in a 1d wire coupled to a slowly moving periodic potential associated with the classical mechanical degree of freedom of the motor. This periodic degree of freedom is set into motion by a bias voltage applied to the 1d electron channel. We investigate the Thouless motor with interacting leads modeled as Luttinger liquids. We show that interactions enhance the energy gap opened by the periodic potential and thus the robustness of the Thouless motor against variations in the chemical potential. We show that the motor degree of freedom can be described as a mobile impurity in a Luttinger liquid obeying Langevin dynamics with renormalized coefficients due to interactions, for which we give explicit expressions.

  17. Motor-operated gearbox efficiency

    SciTech Connect

    DeWall, K.G.; Watkins, J.C.; Bramwell, D.; Weidenhamer, G.H.

    1996-12-01

    Researchers at the Idaho National Engineering Laboratory recently conducted tests investigating the operating efficiency of the power train (gearbox) in motor-operators typically used in nuclear power plants to power motor-operated valves. Actual efficiency ratios were determined from in-line measurements of electric motor torque (input to the operator gearbox) and valve stem torque (output from the gearbox) while the operators were subjected to gradually increasing loads until the electric motor stalled. The testing included parametric studies under reduced voltage and elevated temperature conditions. As part of the analysis of the results, the authors compared efficiency values determined from testing to the values published by the operator manufacturer and typically used by the industry in calculations for estimating motor-operator capabilities. The operators they tested under load ran at efficiencies lower than the running efficiency (typically 50%) published by the operator manufacturer.

  18. New approach to capture and characterize synaptic proteome

    PubMed Central

    Liu, Xin-An; Kadakkuzha, Beena; Pascal, Bruce; Steckler, Caitlin; Akhmedov, Komolitdin; Yan, Long; Chalmers, Michael; Puthanveettil, Sathyanarayanan V.

    2014-01-01

    Little is known regarding the identity of the population of proteins that are transported and localized to synapses. Here we describe a new approach that involves the isolation and systematic proteomic characterization of molecular motor kinesins to identify the populations of proteins transported to synapses. We used this approach to identify and compare proteins transported to synapses by kinesin (Kif) complexes Kif5C and Kif3A in the mouse hippocampus and prefrontal cortex. Approximately 40–50% of the protein cargos identified in our proteomics analysis of kinesin complexes are known synaptic proteins. We also found that the identity of kinesins and where they are expressed determine what proteins they transport. Our results reveal a previously unappreciated role of kinesins in regulating the composition of synaptic proteome. PMID:25352669

  19. Magnetic bearing and motor

    NASA Technical Reports Server (NTRS)

    Studer, Philip A. (Inventor)

    1983-01-01

    A magnetic bearing assembly (10) has an intermediate rotatable section (33) having an outer cylindrical member (30) coaxially suspended by a torsion wire (72) around an axially polarized cylindrical magnet (32). Axial alignment between the pole faces (40-43) of the intermediate section (33) and end surfaces (50-53) of opposed end bells (20, 22) provides a path of least reluctance across intervening air gaps (60-63) for the magnetic flux emanating from magnet (32). Radial dislocation increases the reluctance and creates a radial restoring force. Substitution of radially polarized magnets 107 fixed to a magnetically permeable cylinder (32') and insertion of pairs of armature coil windings (109-112) between the cylinder pair (33') provides an integral magnetic bearing and torsion motor (100) able to provide arcuately limited rotational drive.

  20. Piezoelectric wave motor

    DOEpatents

    Yerganian, Simon Scott

    2003-02-11

    A piezoelectric motor having a stator in which piezoelectric elements are contained in slots formed in the stator transverse to the desired wave motion. When an electric field is imposed on the elements, deformation of the elements imposes a force perpendicular to the sides of the slot, deforming the stator. Appropriate frequency and phase-shifting of the electric field will produce a wave in the stator and motion in a rotor. In a preferred aspect, the piezoelectric elements are configured so that deformation of the elements in the direction of an imposed electric field, generally referred to as the d.sub.33 direction, is utilized to produce wave motion in the stator. In a further aspect, the elements are compressed into the slots so as to minimize tensile stresses on the elements in use.