Collective dynamics of kinesin
Collective dynamics of kinesin
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DOI：
10.1103/physreve.79.031929
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发表时间：
2009-03-01
影响因子：
2.4
通讯作者：
Meyhofer, Edgar
中科院分区：
文献类型：
--
作者：
Hendricks, Adam G.;Epureanu, Bogdan I.;Meyhofer, Edgar
马达蛋白是生物酶，在细胞中将化学能转化为机械功。驱动蛋白-1是一种沿沿着微管转运囊泡的运动蛋白，被广泛认为负责神经元中突触囊泡的顺行转运。单分子技术的进展表明，单个驱动蛋白马达能够以约1 μ m/s的最大速度沿微管沿着进行运动。速度响应于载荷大致线性地减小，直到在约6pN的载荷下达到失速。已经提出了几个理论模型来描述单驱动蛋白马达的稳态运动。越来越多的证据表明，驱动蛋白在细胞中集体发挥作用，从而几个马达以协调的方式工作以运输囊泡。一个瞬态的描述是必要的，以描述集体的动态，耦合电机之间的相互作用，诱导每个电机上的时变力。本文提出了一种能够准确描述瞬态和稳态动力学的驱动蛋白机理模型。蛋白质的每个结构域通过机械势建模。机械电位与每个运动域的化学动力学明确相关。机械模型被用来模拟集体行为的耦合驱动蛋白电机在不同的负载，货物链接器刚度，和电机的数量。为了分析协调运输的模拟，开发了几个度量标准，这些度量标准专门用于表征非线性非光滑振荡器（如驱动蛋白）的同步。模型结果表明，在细胞中，低负载下的耦合电机的动态是松散相关的。当负载增加时，例如当货物遇到障碍物（如另一个囊泡或细胞骨架）时，马达响应于增加的负载而变得更加相关，从而允许它们产生更大的力。增加参与运输的马达的数量并不会明显增加轨迹的尺寸，这意味着大量的马达能够以高度相关的方式运行，而不会完全同步。
Motor proteins are biological enzymes that convert chemical energy to mechanical work in cells. Kinesin-1 is a motor protein that transports vesicles along microtubules and is widely believed to be responsible for anterograde transport of synaptic vesicles in neurons. Advances in single-molecule techniques have shown that single kinesin motors are capable of processive movement along the microtubule at a maximum velocity of approximately 1 mu m/s. The velocity decreases roughly linearly in response to load until reaching stall at a load of approximately 6 pN. Several theoretical models have been proposed that describe the steady-state motion of single kinesin motors. Growing evidence suggests that kinesin functions collectively in cells, whereby several motors work in a coordinated manner to transport a vesicle. A transient description is required to describe collective dynamics, as the interactions among coupled motors induce time-varying forces on each motor. Herein a mechanistic model of kinesin is proposed that is capable of accurately describing transient and steady-state dynamics. Each domain of the protein is modeled via a mechanical potential. The mechanical potentials are related explicitly to the chemical kinetics of each motor domain. The mechanistic model was used to simulate the collective behavior of coupled kinesin motors under varying loads, cargo linker stiffnesses, and numbers of motors. To analyze the simulations of coordinated transport, several metrics were developed that are specifically tailored to characterizing the synchronization of nonlinear nonsmooth oscillators such as kinesin. The model results suggest that, in the cell, the dynamics of coupled motors under low loads are loosely correlated. When the load is increased, such as when the cargo encounters an obstacle such as another vesicle or the cytoskeleton, motors become more correlated in response to increased loads, allowing them to produce greater forces. Increasing the number of motors involved in the transport does not appreciably increase the dimension of the trajectory, implying large numbers of motors are able to function in a highly correlated manner without becoming fully synchronized.