Determinants of contractile forces generated in disorganized actomyosin bundles
Determinants of contractile forces generated in disorganized actomyosin bundles
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DOI：
10.1007/s10237-014-0608-2
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发表时间：
2015-04-01
影响因子：
3.5
通讯作者：
Kim, Taeyoon
中科院分区：
文献类型：
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作者：
Kim, Taeyoon
肌动球蛋白机制是一种基本的引擎，主要由肌动蛋白丝，分子马达和被动交联剂组成，产生非肌肉细胞生物过程所需的机械力，如细胞迁移，胞质分裂和形态发生。虽然肌动球蛋白机制中的关键元素的分子和物理性质已经得到了很好的表征，但仍不清楚肌动球蛋白网络和束中的宏观力的建立和消散如何取决于单个细胞骨架组分及其局部相互作用的微观性质。为了弥合宏观和微观尺度之间的差距，我们已经开发了一个三维计算模型的肌动球蛋白束夹在弹性基板与最小的组件：肌动蛋白丝，被动交联剂，和主动马达。我们的模型考虑了以前的研究所忽略的几个关键特征，尽管它们对力的产生具有重要意义，例如电机的现实结构和动力学。使用该模型，我们系统地研究了如何在肌动球蛋白束的净张力是通过电机和交联剂之间的相互作用。我们证明了电机可以在没有交联剂的情况下以非常低效、不稳定的方式在束上产生大的张力。交联剂有助于电机产生最大的势能，并增强整体连接性，从而提高效率和稳定性。我们进一步表明，交联剂的行为作为一个分子离合器与可调摩擦，这有相当明显的影响，根据其交联角的净张力。我们还研究了在张力产生过程中张力和压缩力之间的对称性破缺的来源，并讨论了肌动蛋白丝的长度和动力学以及弹性基底的刚度如何影响所产生的张力。
Actomyosin machinery is a fundamental engine consisting mostly of actin filaments, molecular motors, and passive cross-linkers, generating mechanical forces required for biological processes of non-muscle cells such as cell migration, cytokinesis, and morphogenesis. Although the molecular and physical properties of key elements in the actomyosin machinery have been characterized well, it still remains unclear how macroscopic force buildup and dissipation in actomyosin networks and bundles depend on the microscopic properties of individual cytoskeletal components and their local interactions. To bridge such a gap between macroscopic and microscopic scales, we have developed a three-dimensional computational model of actomyosin bundles clamped to an elastic substrate with minimal components: actin filaments, passive cross-linkers, and active motors. Our model accounts for several key features neglected by previous studies despite their significance for force generation, such as realistic structure and kinetics of the motors. Using the model, we systematically investigated how net tension in actomyosin bundles is governed via interplay between motors and cross-linkers. We demonstrated motors can generate large tension on a bundle in the absence of cross-linkers in a very inefficient, unstable manner. Cross-linkers help motors to generate their maximum potential forces as well as enhance overall connectivity, leading to much higher efficiency and stability. We showed further that the cross-linkers behave as a molecular clutch with tunable friction which has quite distinct effects on net tension depending on their cross-linking angles. We also examined the source of symmetry breaking between tensile and compressive forces during tension generation process and discussed how the length and dynamics of actin filaments and the stiffness of the elastic substrate can affect the generated tension.