The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Ajay Gopinathan - One of the best experts on this subject based on the ideXlab platform.
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Cargo diffusion shortens single-kinesin runs at low Viscous Drag
Scientific reports, 2019Co-Authors: John O. Wilson, David A. Quint, Ajay GopinathanAbstract:Molecular motors such as kinesin-1 drive active, long-range transport of cargos along microtubules in cells. Thermal diffusion of the cargo can impose a randomly directed, fluctuating mechanical load on the motor carrying the cargo. Recent experiments highlighted a strong asymmetry in the sensitivity of single-kinesin run length to load direction, raising the intriguing possibility that cargo diffusion may non-trivially influence motor run length. To test this possibility, here we employed Monte Carlo-based simulations to evaluate the transport of cargo by a single kinesin. Our simulations included physiologically relevant Viscous Drag on the cargo and interrogated a large parameter space of cytoplasmic viscosities, cargo sizes, and motor velocities that captures their respective ranges in living cells. We found that cargo diffusion significantly shortens single-kinesin runs. This diffusion-based shortening is countered by Viscous Drag, leading to an unexpected, non-monotonic variation in run length as Viscous Drag increases. To our knowledge, this is the first identification of a significant effect of cargo diffusion on motor-based transport. Our study highlights the importance of cargo diffusion and load-detachment kinetics on single-motor functions under physiologically relevant conditions.
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Cargo diffusion shortens single-kinesin runs at low Viscous Drag
2018Co-Authors: John O. Wilson, David A. Quint, Ajay GopinathanAbstract:Molecular motors are mechanoenzymes that actively drive long-range transport in cells. Thermal diffusion of the cargo can result in mechanical load on the motor carrying the cargo; the direction of this diffusion-based load is not correlated with motor motion. Recent single molecule-based experiments highlighted a strong asymmetric dependence of the run length of the single kinesin-1 motor on load direction, raising the intriguing possibility that thermal diffusion of the cargo may non-trivially influence the run length of the motor carrying the cargo. To test this possibility, here we employed Monte Carlo-based stochastic simulations to evaluate the transport of single-kinesin cargos over a large parameter space of physiologically relevant solution viscosities, cargo sizes, and motor velocities. Our simulations uncovered a previously unexplored, significant shortening effect of cargo diffusion on single-kinesin run length. This effect is non-monotonically influenced by Viscous Drag force on the cargo, which biases the effect of cargo diffusion toward the hindering direction. The non-monotonic variation of cargo run length with Drag force is the direct result of the asymmetric response of kinesin's run length to load direction. Our findings may be important for understanding the diverse characteristics of cargo transport, including run length, observed in living cells.
John O. Wilson - One of the best experts on this subject based on the ideXlab platform.
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Cargo diffusion shortens single-kinesin runs at low Viscous Drag
Scientific reports, 2019Co-Authors: John O. Wilson, David A. Quint, Ajay GopinathanAbstract:Molecular motors such as kinesin-1 drive active, long-range transport of cargos along microtubules in cells. Thermal diffusion of the cargo can impose a randomly directed, fluctuating mechanical load on the motor carrying the cargo. Recent experiments highlighted a strong asymmetry in the sensitivity of single-kinesin run length to load direction, raising the intriguing possibility that cargo diffusion may non-trivially influence motor run length. To test this possibility, here we employed Monte Carlo-based simulations to evaluate the transport of cargo by a single kinesin. Our simulations included physiologically relevant Viscous Drag on the cargo and interrogated a large parameter space of cytoplasmic viscosities, cargo sizes, and motor velocities that captures their respective ranges in living cells. We found that cargo diffusion significantly shortens single-kinesin runs. This diffusion-based shortening is countered by Viscous Drag, leading to an unexpected, non-monotonic variation in run length as Viscous Drag increases. To our knowledge, this is the first identification of a significant effect of cargo diffusion on motor-based transport. Our study highlights the importance of cargo diffusion and load-detachment kinetics on single-motor functions under physiologically relevant conditions.
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Cargo diffusion shortens single-kinesin runs at low Viscous Drag
2018Co-Authors: John O. Wilson, David A. Quint, Ajay GopinathanAbstract:Molecular motors are mechanoenzymes that actively drive long-range transport in cells. Thermal diffusion of the cargo can result in mechanical load on the motor carrying the cargo; the direction of this diffusion-based load is not correlated with motor motion. Recent single molecule-based experiments highlighted a strong asymmetric dependence of the run length of the single kinesin-1 motor on load direction, raising the intriguing possibility that thermal diffusion of the cargo may non-trivially influence the run length of the motor carrying the cargo. To test this possibility, here we employed Monte Carlo-based stochastic simulations to evaluate the transport of single-kinesin cargos over a large parameter space of physiologically relevant solution viscosities, cargo sizes, and motor velocities. Our simulations uncovered a previously unexplored, significant shortening effect of cargo diffusion on single-kinesin run length. This effect is non-monotonically influenced by Viscous Drag force on the cargo, which biases the effect of cargo diffusion toward the hindering direction. The non-monotonic variation of cargo run length with Drag force is the direct result of the asymmetric response of kinesin's run length to load direction. Our findings may be important for understanding the diverse characteristics of cargo transport, including run length, observed in living cells.
Sandip Ghosal - One of the best experts on this subject based on the ideXlab platform.
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Electrokinetic-flow-induced Viscous Drag on a tethered DNA inside a nanopore.
Physical review. E Statistical nonlinear and soft matter physics, 2007Co-Authors: Sandip GhosalAbstract:Recent work has shown that the resistive force arising from Viscous effects within the pore region could explain observed translocation times in certain experiments involving voltage-driven translocations of DNA through nanopores [Ghosal, Phys. Rev. E 71, 051904 (2006); Phys. Rev. Lett. 98, 238104 (2007)]. The electrokinetic flow inside the pore and the accompanying Viscous effects also play a crucial role in the interpretation of experiments where the DNA is immobilized inside a nanopore [Keyser, Nat. Phys. 2, 473 (2006)]. In this paper the Viscous force is explicitly calculated for a nanopore of cylindrical geometry. It is found that the reductions of the tether force due to Viscous Drag and due to charge reduction by Manning condensation are of similar size. The result is of importance in the interpretation of experimental data on tethered DNA.
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Electrokinetic-flow-induced Viscous Drag on a tethered DNA inside a nanopore.
Physical Review E, 2007Co-Authors: Sandip GhosalAbstract:Recent work has shown that the resistive force arising from Viscous effects within the pore region could explain observed translocation times in certain experiments involving voltage-driven translocations of DNA through nanopores [Ghosal, Phys. Rev. E 71, 051904 (2006); Phys. Rev. Lett. 98, 238104 (2007)]. The electrokinetic flow inside the pore and the accompanying Viscous effects also play a crucial role in the interpretation of experiments where the DNA is immobilized inside a nanopore [Keyser et al., Nat. Phys. 2, 473 (2006)]. In this paper the Viscous force is explicitly calculated for a nanopore of cylindrical geometry. It is found that the reductions of the tether force due to Viscous Drag and due to charge reduction by Manning condensation are of similar size. The result is of importance in the interpretation of experimental data on tethered DNA.
David A. Quint - One of the best experts on this subject based on the ideXlab platform.
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Cargo diffusion shortens single-kinesin runs at low Viscous Drag
Scientific reports, 2019Co-Authors: John O. Wilson, David A. Quint, Ajay GopinathanAbstract:Molecular motors such as kinesin-1 drive active, long-range transport of cargos along microtubules in cells. Thermal diffusion of the cargo can impose a randomly directed, fluctuating mechanical load on the motor carrying the cargo. Recent experiments highlighted a strong asymmetry in the sensitivity of single-kinesin run length to load direction, raising the intriguing possibility that cargo diffusion may non-trivially influence motor run length. To test this possibility, here we employed Monte Carlo-based simulations to evaluate the transport of cargo by a single kinesin. Our simulations included physiologically relevant Viscous Drag on the cargo and interrogated a large parameter space of cytoplasmic viscosities, cargo sizes, and motor velocities that captures their respective ranges in living cells. We found that cargo diffusion significantly shortens single-kinesin runs. This diffusion-based shortening is countered by Viscous Drag, leading to an unexpected, non-monotonic variation in run length as Viscous Drag increases. To our knowledge, this is the first identification of a significant effect of cargo diffusion on motor-based transport. Our study highlights the importance of cargo diffusion and load-detachment kinetics on single-motor functions under physiologically relevant conditions.
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Cargo diffusion shortens single-kinesin runs at low Viscous Drag
2018Co-Authors: John O. Wilson, David A. Quint, Ajay GopinathanAbstract:Molecular motors are mechanoenzymes that actively drive long-range transport in cells. Thermal diffusion of the cargo can result in mechanical load on the motor carrying the cargo; the direction of this diffusion-based load is not correlated with motor motion. Recent single molecule-based experiments highlighted a strong asymmetric dependence of the run length of the single kinesin-1 motor on load direction, raising the intriguing possibility that thermal diffusion of the cargo may non-trivially influence the run length of the motor carrying the cargo. To test this possibility, here we employed Monte Carlo-based stochastic simulations to evaluate the transport of single-kinesin cargos over a large parameter space of physiologically relevant solution viscosities, cargo sizes, and motor velocities. Our simulations uncovered a previously unexplored, significant shortening effect of cargo diffusion on single-kinesin run length. This effect is non-monotonically influenced by Viscous Drag force on the cargo, which biases the effect of cargo diffusion toward the hindering direction. The non-monotonic variation of cargo run length with Drag force is the direct result of the asymmetric response of kinesin's run length to load direction. Our findings may be important for understanding the diverse characteristics of cargo transport, including run length, observed in living cells.
Christoph A. Naumann - One of the best experts on this subject based on the ideXlab platform.
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Cellular Mechano-Stimulation by Adjusting the Viscous Drag of Cell-Substrate Linkers in Biomembrane-Mimicking Cell Substrates
Biophysical Journal, 2012Co-Authors: Yu-hung Lin, Daniel E. Minner, Lena Lautscham, Andreas Schoenborn, Wolfgang H. Goldmann, Ben Fabry, Christoph A. NaumannAbstract:It is now widely recognized that substrate viscoelasticity may have a profound impact on cellular fate and function. However, the underlying mechanisms of cellular mechano-sensing remain a topic of open debate. Traditionally, cellular mechano-regulation was accomplished using polymeric substrates of adjustable viscoelasticity with immobilized cell linkers. Here, we present an alternative strategy of cellular mechano-regulation, in which the Viscous Drag of cell-substrate linkers is altered by the number of lipid bilayers in a polymer-tethered multi-bilayer stack.
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Mechano-Stimulation of Fibroblasts by Adjusting Viscous Drag of Mobile Cell Linkers in Biomembrane-Mimicking Substrates
Biophysical Journal, 2011Co-Authors: Daniel E. Minner, Yu-hung Lin, Andreas Schoenborn, Wolfgang H. Goldmann, Ben Fabry, Christoph A. NaumannAbstract:Recent advancements in the design of polymeric substrates of tunable rigidity have shown that cells probe the viscoelasticity of their environment through an adaptive process of focal contact assembly/disassembly that critically affects cell adhesion and morphology. However, the specific mechanisms of this process of mechano-sensitivity have not yet been fully uncovered, in part due to the limitations of existing engineered cell substrates, which are characterized by immobilized cell linkers. To overcome this limitation, we here present a biomembrane-mimicking cell substrate based on polymer-tethered lipid muli-bilayers, in which laterally mobile cell linkers enable the free assembly and disassembly of focal adhesions. In this experimental platform, the mechano-stimulation of plated cells is accomplished by altering the Viscous Drag of cell linkers through the number of lipid bilayers in the solid-supported multi-bilayer stack. Results from microscopy experiments are discussed, which illustrate that the number of bilayers in the multi-bilayer stack has a profound impact on various cellular properties of plated 3T3 fibroblasts, including adhesion, morphology, shape fluctuations, migration, and cytoskeletal organization.Furthermore, this biomembrane-mimicking substrate is integrated into a force traction microscopy assay, which confirms that the presence of the fluid multi-bilayer system leads to a notable reduction in cellular traction forces. Our experiments illustrate that the described biomembrane-mimicking cell substrate is particularly well suited to monitor plated cells under conditions of weak force transduction conditions between cells and underlying substrate.
