Myosin and [Formula: see text]-actinin regulation of stress fiber contractility under tensile stress.
Myosin and [Formula: see text]-actinin regulation of stress fiber contractility under tensile stress.
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DOI：
10.1038/s41598-023-35675-7
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发表时间：
2023-05-29
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
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应力纤维是调节细胞机械感觉和力传导的肌动球蛋白束。应力纤维通过黏附复合物与细胞外基质相互作用，是由肌球蛋白马达和交联蛋白调控的高度动态结构。在外力（如拉力）的作用下，应力纤维的结构会随着外力的变化而改变，表现出粘弹性材料的特性。应力纤维的结构重塑与收缩力的产生之间的关系尚不清楚。在这项工作中，我们使用分子模拟平台MEDYAN模拟应力纤维的机械化学动力学和力的产生。我们将应力纤维建模为两个连接的双极束，两端连接到焦点粘附复合物。模拟应力纤维产生收缩力，收缩力由肌凝蛋白马达和-肌动蛋白交联剂调节。我们发现应力纤维通过减少肌动蛋白丝之间的距离来增加交联剂的结合，从而增强收缩性，而这种结构重塑能力取决于交联剂的周转率。在拉伸拉力作用下，应力纤维收缩力瞬间增大，随后缓慢松弛进入新的稳态。拉力后的新稳态收缩力仅取决于肌动蛋白束之间的重叠，而短期收缩力的增强对拉伸拉力距离敏感。我们进一步表明，这种机械响应对交联剂的周转率也很敏感。我们的研究结果为应力纤维力学提供了新的见解，对理解细胞对机械信号的适应具有重要意义。
Stress fibers are actomyosin bundles that regulate cellular mechanosensation and force transduction. Interacting with the extracellular matrix through focal adhesion complexes, stress fibers are highly dynamic structures regulated by myosin motors and crosslinking proteins. Under external mechanical stimuli such as tensile forces, the stress fiber remodels its architecture to adapt to external cues, displaying properties of viscoelastic materials. How the structural remodeling of stress fibers is related to the generation of contractile force is not well understood. In this work, we simulate mechanochemical dynamics and force generation of stress fibers using the molecular simulation platform MEDYAN. We model stress fiber as two connecting bipolar bundles attached at the ends to focal adhesion complexes. The simulated stress fibers generate contractile force that is regulated by myosin motors and -actinin crosslinkers. We find that stress fibers enhance contractility by reducing the distance between actin filaments to increase crosslinker binding, and this structural remodeling ability depends on the crosslinker turnover rate. Under tensile pulling force, the stress fiber shows an instantaneous increase of the contractile forces followed by a slow relaxation into a new steady state. While the new steady state contractility after pulling depends only on the overlap between actin bundles, the short-term contractility enhancement is sensitive to the tensile pulling distance. We further show that this mechanical response is also sensitive to the crosslinker turnover rate. Our results provide new insights into the stress fiber mechanics that have significant implications for understanding cellular adaptation to mechanical signaling.
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影响因子：
3.4
作者：
Freedman, Simon L.;Banerjee, Shiladitya;Dinner, Aaron R.
通讯作者：
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DOI：
10.1073/pnas.1820814116
发表时间：
2019-08-13
影响因子：
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作者：
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