运用有限元与MONTE CARLO相耦合的数值方法分析在循环载荷作用下应力纤维的力学行为

Stress fiber (SF) widely exists in eukaryotic cells and is important in morphogenesis, differentiation, development, etc. It is one essential component of cellular mechanosensing apparatus. Experiments showed that, upon cyclic stretch, initially randomly oriented SFs gradually reoriented almost perpendicular to the stretch direction. Further experiments demonstrated that the duration of whole reorientation process strongly depended on the stretch amplitude and stretch frequency and it underwent a phase change around 1 Hz. To better understand these experimental results, here we propose to study the mechanical behavior of SFs upon cyclic stretch. We will build up mechanics models for SFs, which will be implemented within a coupled finite element method and Monte Carlo simulation scheme. We will then investigate the underlying principles of the coordinated action of multiple myosin motors in a SF. We also aim to provide quantitative description of the relation between force and velocity during SF contraction. Our work would provide important insights in understanding cellular mechanosensing, which is critical in various cellular processes.

应力纤维广泛存在于真核细胞中，是细胞感知机械信号的重要组分，在细胞的形态发生、细胞分化、和组织形成等众多生理过程中都起着重要的作用。实验显示初始随机取向的应力纤维在循环载荷作用下逐渐变得很规则。进一步的实验表明，该取向调整所用的时间与循环载荷的幅度和频率密切相关，并在重要的生理频率1Hz 附近出现相变。为了深入理解这些实验结果，我们选择应力纤维在循环载荷下的力学行为作为研究对象，在理论建模的基础上，采用有限元与MONTE CARLO 相耦合的数值研究方案来探索分布于其上的分子马达之间的协调作用的机理，并寻找应力纤维的力与收缩速度的定量关系。我们的研究成果将为理解细胞是如何感知机械信号的这一生理过程提供重要的信息。

应力纤维是细胞感知机械信号的重要组分，在众多生理过程中都起着重要的作用。我们采用多尺度理论建模、数值模拟的方法，研究了与应力纤维相关的结构与过程。利用单个分子马达化学力学循环的动力学模型，我们定量分析了不同核苷酸状态的肌球马达从细纤维上断开的速率。 建立了两种类型的单分子逆锁键模型，分析在各种变载荷条件下单分子逆锁键的力学行为。通过建立了细胞感应机械信号的理论模型，揭示了在循环载荷作用下细胞取向的机理；在Annual Reviews of Biophysics期刊上发表了关于细胞与弹性基体相互作用的综述论文，指出该领域的挑战与今后发展的主要方向。共发表SCI 论文9篇，包括Nano Lett.、Annual Reviews of Biophysics等国际顶级期刊，培养了多名硕博研究生，并多次参与国内与国际的学术交流。