The role of the Arp2/3 complex in shaping the dynamics and structures of branched actomyosin networks
The role of the Arp2/3 complex in shaping the dynamics and structures of branched actomyosin networks
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DOI：
10.1073/pnas.1922494117
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发表时间：
2020-05-19
影响因子：
11.1
通讯作者：
Cheung, Margaret S.
中科院分区：
文献类型：
--
作者：
Liman, James;Bueno, Carlos;Cheung, Margaret S.
肌动球蛋白网络赋予细胞移动和分裂的能力。这些网络在运动、蛋白质行走和肌动蛋白聚合等活跃的耗能过程的推动下收缩和扩张。肌动蛋白的动态也受肌动蛋白结合蛋白的调节，例如肌动蛋白相关蛋白2/3(Arp2/3)复合体。这种复合体产生分枝的细丝，从而改变网络的整体组织。在这项工作中，使用一个计算模型(活性网络的机械力化学动力学[Medyan])研究了Arp2/3引起的分支诱导的重组过程中肌动蛋白动态组装的时空模式；该模型模拟了由于化学反应而导致的肌动蛋白网络动力学，其速率受到快速机械平衡的调节。我们发现，分支的肌球蛋白网络的松弛速度明显慢于未分支的网络。此外，分支网络会经历罕见的抽搐运动，即“雪崩”，从而释放网络中的压力。这些雪崩与分支网络显示的机械连接细丝的更不均匀分布有关。这些由不断增长的肌动球蛋白网络的边际稳定性引起的远离平衡的事件，为最近在实验中看到的“细胞地震”提供了一种可能的机制。
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 (mechanochemical dynamics of active networks [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.