Branching and capping determine the force-velocity relationships of branching actin networks.
Branching and capping determine the force-velocity relationships of branching actin networks.
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DOI：
10.1088/1478-3975/10/1/016004
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发表时间：
2013-02
期刊：
影响因子：
2
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Smith DB;Liu J
分支肌动蛋白网络是驱动细胞运动的主要引擎。衡量发动机有效性的标准是发动机在给定阻力下能够产生的速度，即力-速度关系。凹形力-速度关系由力不敏感区域组成，表明自适应响应。相反，凸的力-速度关系将反映被动响应。即使在体外实验中，分支肌动蛋白网络也可以表现出凹形和凸形的力-速度曲线。然而，能够解释这两条力-速度曲线的确切机制尚不清楚。我们进行了基于代理的随机模拟来探索这样的机制。我们发现了分支肌动蛋白网络的一种新兴行为：在抵抗时，它通过增加与负载接触的细丝数量来重塑自身。重塑受到分支事件的青睐并受到上限的限制。力-速度关系取决于分支肌动蛋白网络的内在动力学和负载之间的相对时间尺度。在遇到阻力后不久（~秒），肌动蛋白网络的力-速度关系总是凸的，因为它没有足够的时间来重塑自身。凹力-速度关系需要在较长的时间尺度（约几十秒到几分钟）内进行网络重塑，并且相对于上限而言，需要更快的分支事件。此外，我们的模型解释了肌动蛋白网络的力-速度关系中观察到的滞后现象。因此，我们的模型建立了一个统一的机制，可以解释在分支肌动蛋白网络中观察到的凸和凹力-速度关系。
A branching actin network is the major engine that drives cell motility. A measure of the effectiveness of an engine is the velocity the engine is able to produce at a given resistance – the force-velocity relationship. Concave force-velocity relationships consist of a force-insensitive region, indicative of an adaptive response. In contrast, convex force-velocity relationships would reflect a passive response. Even in in vitro experiments, branching actin networks can exhibit both concave and convex force-velocity curves. However, the exact mechanism that can explain both force-velocity curves is not yet known. We carried out an agent-based stochastic simulation to explore such a mechanism. We discovered an emergent behavior of a branching actin network: Upon resistance, it remodels itself by increasing the number of filaments growing in contact with the load. The remodeling is favored by branching events and limited by capping. The force-velocity relationship hinges on the relative time-scale between the intrinsic kinetics of the branching actin network and the loading. Shortly after encountering resistance (~ seconds), the force-velocity relationship of the actin network is always convex, as it does not have enough time to remodel itself. A concave force-velocity relationship requires network remodeling at longer time-scales (~ tens of seconds to minutes) and the faster branching event relative to capping. Furthermore, our model explains the observed hysteresis in the force-velocity relationship of actin networks. Our model thus establishes a unified mechanism that can account for both convex and concave force-velocity relationships observed in branching actin networks.
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