Cargo diffusion shortens single-kinesin runs at low viscous drag.
Cargo diffusion shortens single-kinesin runs at low viscous drag.
复制标题
货物扩散缩短了单驱动蛋白在低粘滞阻力下的运行时间。
DOI：
10.1038/s41598-019-40550-5
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Xu,Jing
中科院分区：
文献类型：
--
作者：
Wilson,JohnO;Quint,DavidA;Gopinathan,Ajay;Xu,Jing
分子马达如驱动蛋白-1驱动细胞中的货物沿沿着的主动、长距离运输。货物的热扩散可在承载货物的马达上施加随机定向的波动机械负载。最近的实验强调了一个强大的不对称性的敏感性，单驱动蛋白运行长度负载方向，提出了有趣的可能性，货物扩散可能会影响电机运行长度。为了测试这种可能性，在这里，我们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，并询问了细胞质粘度，货物大小和电机速度的大参数空间，这些参数空间捕获了它们在活细胞中的相应范围。我们发现，货物扩散显着缩短单驱动蛋白运行。这种基于扩散的缩短被粘性阻力抵消，导致当粘性阻力增加时运行长度的意外的非单调变化。据我们所知，这是第一次确认货物扩散对机动运输的重大影响。我们的研究强调了在生理相关条件下货物扩散和负荷分离动力学对单运动功能的重要性。
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.