Abstract

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.

Details

Title
Cargo diffusion shortens single-kinesin runs at low viscous drag
Author
Wilson, John O 1 ; Quint, David A 2 ; Gopinathan Ajay 3 ; Xu, Jing 1 

 University of California, Department of Physics, Merced, USA (GRID:grid.266096.d) (ISNI:0000 0001 0049 1282) 
 University of California, NSF CREST: Center for Cellular and Biomolecular Machines, Merced, USA (GRID:grid.266096.d) (ISNI:0000 0001 0049 1282) 
 University of California, Department of Physics, Merced, USA (GRID:grid.266096.d) (ISNI:0000 0001 0049 1282); University of California, NSF CREST: Center for Cellular and Biomolecular Machines, Merced, USA (GRID:grid.266096.d) (ISNI:0000 0001 0049 1282) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2190113038
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.