Department of Physics, University of California, Merced, California, 95343, USA.
NSF CREST: Center for Cellular and Biomolecular Machines, University of California, Merced, California, 95343, USA.
Sci Rep. 2019 Mar 11;9(1):4104. doi: 10.1038/s41598-019-40550-5.
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.
分子马达（如驱动蛋白-1）可沿细胞中的微管驱动货物进行主动的、长程运输。货物的热扩散会对携带货物的马达施加随机定向、波动的机械负载。最近的实验强调了单驱动蛋白运行长度对负载方向的敏感性存在强烈的不对称性，这提出了一个有趣的可能性，即货物扩散可能会对马达的运行长度产生重要影响。为了验证这种可能性，我们在这里采用基于蒙特卡罗的模拟来评估单个驱动蛋白的货物运输。我们的模拟包括对货物的生理相关粘性阻力，并在细胞质粘度、货物大小和马达速度的大参数空间中进行了询问，这些参数空间涵盖了活细胞中它们各自的范围。我们发现货物扩散会显著缩短单驱动蛋白的运行。这种基于扩散的缩短会被粘性阻力抵消，导致运行长度随着粘性阻力的增加而出现出人意料的非单调变化。据我们所知，这是首次确定货物扩散对基于马达的运输有显著影响。我们的研究强调了在生理相关条件下，货物扩散和负载脱离动力学对单个马达功能的重要性。
