The role of the Arp2/3 complex in shaping the dynamics and structures of branched actomyosin networks

Actomyosin networks give cells the ability to move and divide. These networks contract and expand while being driven by active energy-consuming processes such as motor protein walking and actin polymerization. Actin dynamics is also regulated by actin-binding proteins, such as the actin-related protein 2/3 (Arp2/3) complex. This complex generates branched filaments thereby changing the overall organization of the network. In this work, the spatiotemporal patterns of dynamical actin assembly accompanying the branching-induced reorganization caused by Arp2/3 were studied using a computational model (MEDYAN); this model simulates actomyosin network dynamics as a result of chemical reactions whose rates are modulated by rapid mechanical equilibration. We show that branched actomyosin networks relax significantly more slowly than do unbranched networks. Also, branched networks undergo rare convulsive movements, “avalanches”, that release strain in the network. These avalanches are associated with the more heterogeneous distribution of mechanically-linked filaments displayed by branched networks. These far-from equilibrium events arising from the marginal stability of growing actomyosin networks provide a possible mechanism of the “cytoquakes” recently seen in experiments.肌动蛋白-肌球蛋白网络赋予细胞运动与分裂的能力。该网络在马达蛋白行走、肌动蛋白聚合等主动耗能过程的驱动下发生收缩与扩张。肌动蛋白动力学同时受肌动蛋白结合蛋白的调控，例如肌动蛋白相关蛋白2/3（Arp2/3）复合物。该复合物可生成分支状丝状体，进而改变网络的整体组织结构。本研究采用计算模型MEDYAN，对Arp2/3介导的分支诱导重组所伴随的动态肌动蛋白组装时空模式展开了研究；该模型通过速率受快速机械平衡调控的化学反应，模拟肌动蛋白-肌球蛋白网络的动态演化过程。研究结果显示，分支状肌动蛋白-肌球蛋白网络的松弛速率显著慢于无分支网络。此外，分支状网络会出现罕见的痉挛式“雪崩”运动，该过程可释放网络内的蓄积应力。这类雪崩现象与分支状网络所呈现的机械连接丝状体非均匀分布特征紧密相关。由生长中肌动蛋白-肌球蛋白网络的边际稳定性所引发的此类远离平衡态事件，为实验中近期观测到的“细胞震（cytoquakes）”提供了一种潜在的作用机制。