Actin bundle architecture and mechanics regulate myosin II force generation
Actin bundle architecture and mechanics regulate myosin II force generation
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DOI：
10.1016/j.bpj.2021.03.026
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发表时间：
2021-05-18
影响因子：
3.4
通讯作者：
Gardel, Margaret L.
中科院分区：
文献类型：
--
作者：
Weirich, Kimberly L.;Stam, Samantha;Gardel, Margaret L.
肌动蛋白细胞骨架是一种柔软的结构材料，是细胞分裂、运动和货物运输等生物过程的基础。交联的肌动蛋白丝自组织成无数的架构，从无序的网状有序束，这是假设控制肌动球蛋白力的产生，调节细胞迁移，形状和粘附。在这里，我们使用荧光显微镜和模拟研究如何肌动蛋白束结构与不同的极性，间距和刚度的影响肌球蛋白II的动力学和力的产生。显微镜观察显示，刚性交联剂形成的混合极性束支持缓慢的双向肌球蛋白II细丝运动，间断的停滞运动时期。模拟显示，这些位置的停滞肌球蛋白运动对应于持续的，高的力在平衡的肌动蛋白丝极性的区域。相比之下，由顺应性大交联剂形成的混合极性束支持快速、双向运动而没有陷阱。模拟结果表明，陷阱的持续时间是直接相关的力的大小和所观察到的增加的速度对应于较低的力从增加的束顺应性和细丝间距。我们的研究结果表明，肌动蛋白组件的微观结构调节肌球蛋白II力的动态和大小，突出了生物材料中的结构和力学在调节力的重要性。
The actin cytoskeleton is a soft, structural material that underlies biological processes such as cell division, motility, and cargo transport. The cross-linked actin filaments self-organize into a myriad of architectures, from disordered meshworks to ordered bundles, which are hypothesized to control the actomyosin force generation that regulates cell migration, shape, and adhesion. Here, we use fluorescence microscopy and simulations to investigate how actin bundle architectures with varying polarity, spacing, and rigidity impact myosin II dynamics and force generation. Microscopy reveals that mixed-polarity bundles formed by rigid cross-linkers support slow, bidirectional myosin II filament motion, punctuated by periods of stalled motion. Simulations reveal that these locations of stalled myosin motion correspond to sustained, high forces in regions of balanced actin filament polarity. By contrast, mixed-polarity bundles formed by compliant, large cross-linkers support fast, bidirectional motion with no traps. Simulations indicate that trap duration is directly related to force magnitude and that the observed increased velocity corresponds to lower forces resulting from both the increased bundle compliance and filament spacing. Our results indicate that the microstructures of actin assemblies regulate the dynamics and magnitude of myosin II forces, highlighting the importance of architecture and mechanics in regulating forces in biological materials.