Load Adaptation of Lamellipodial Actin Networks
Load Adaptation of Lamellipodial Actin Networks
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DOI：
10.1016/j.cell.2017.07.051
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发表时间：
2017-09-21
期刊：
影响因子：
64.5
通讯作者：
Sixt, Michael
中科院分区：
文献类型：
--
作者：
Mueller, Jan;Szep, Gregory;Sixt, Michael
肌动蛋白细丝对膜进行聚合，促进内吞作用、囊泡运输和细胞运动。体外重建研究表明，肌动蛋白网络的结构和动力学对机械力做出反应。我们证明，当膜张力被调节时，迁移细胞的板脂肌动蛋白对机械负荷做出反应。在稳定状态下，迁移的细胞丝呈现典型的树枝状几何形状，由Arp2/3生成的70度分支点定义。张力的增加会触发具有更宽角度范围的致密网络，而张力的降低会导致由垂直于质膜生长的细丝主导的稀疏构型的转变。我们发现，这些反应来自分支肌动蛋白的几何形状：当每根细丝的负荷减少时，伸长速度加快，垂直细丝逐渐优于其他细丝，因为它们聚合到膜的距离最短，在那里它们受到保护，不会被封顶。这种网络固有的几何适应机制可以调整突出力，以响应机械载荷。
Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70 degrees branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.