Institute for Physical Science and Technology, University of Maryland, College Park, MD, USA.
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Sci Rep. 2023 May 29;13(1):8662. doi: 10.1038/s41598-023-35675-7.
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 [Formula: see text]-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.
应力纤维是肌动球蛋白纤维束，可调节细胞机械感觉和力转导。通过粘着斑复合物与细胞外基质相互作用，应力纤维是由肌球蛋白马达和交联蛋白调节的高度动态结构。在外部机械刺激（如张力）下，应力纤维重塑其结构以适应外部线索，表现出粘弹性材料的特性。应力纤维的结构重塑如何与收缩力的产生相关，目前还不太清楚。在这项工作中，我们使用分子模拟平台 MEDYAN 模拟了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，两端附着在粘着斑复合物上。模拟的应力纤维产生的收缩力受肌球蛋白马达和 α-辅肌动蛋白交联剂的调节。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，从而增强收缩力，这种结构重塑能力取决于交联剂的周转率。在拉伸拉力下，应力纤维表现出收缩力的瞬时增加，随后缓慢松弛到新的稳定状态。虽然拉伸后的新稳定状态收缩力仅取决于肌动蛋白束的重叠，但短期收缩力增强对拉伸距离敏感。我们进一步表明，这种机械响应也对交联剂周转率敏感。我们的结果为理解细胞对机械信号的适应提供了应力纤维力学的新见解。
