Das Shuvrangsu, Ippolito Alberto, McGarry Patrick, Deshpande Vikram S
Department of Engineering, Cambridge University, Trumpington St, Cambridge CB2 1PZ, UK.
Department of Mechanical and Biomedical Engineering, National University of Ireland, University Road, Galway H91 CF50, Ireland.
PNAS Nexus. 2022 Sep 22;1(5):pgac199. doi: 10.1093/pnasnexus/pgac199. eCollection 2022 Nov.
Cyclic strain avoidance, the phenomenon of cell and cytoskeleton alignment perpendicular to the direction of cyclic strain of the underlying 2D substrate, is an important characteristic of the adherent cell organization. This alignment has typically been attributed to the stress-fiber reorganization although observations clearly show that stress-fiber reorganization under cyclic loading is closely coupled to cell morphology and reorientation of the cells. Here, we develop a statistical mechanics framework that couples the cytoskeletal stress-fiber organization with cell morphology under imposed cyclic straining and make quantitative comparisons with observations. The framework accurately predicts that cyclic strain avoidance stems primarily from cell reorientation away from the cyclic straining rather than cytoskeletal reorganization within the cell. The reorientation of the cell is a consequence of the cell lowering its free energy by largely avoiding the imposed cyclic straining. Furthermore, we investigate the kinetics of the cyclic strain avoidance mechanism and demonstrate that it emerges primarily due to the rigid body rotation of the cell rather than via a trajectory involving cell straining. Our results provide clear physical insights into the coupled dynamics of cell morphology and stress-fibers, which ultimately leads to cellular organization in cyclically strained tissues.
循环应变规避，即细胞和细胞骨架垂直于二维基底循环应变方向排列的现象，是贴壁细胞组织的一个重要特征。这种排列通常归因于应力纤维的重组，尽管观察结果清楚地表明，循环加载下的应力纤维重组与细胞形态和细胞重定向密切相关。在这里，我们开发了一个统计力学框架，该框架将细胞骨架应力纤维组织与施加循环应变下的细胞形态联系起来，并与观察结果进行定量比较。该框架准确地预测，循环应变规避主要源于细胞远离循环应变的重定向，而不是细胞内的细胞骨架重组。细胞的重定向是细胞通过很大程度上避免施加的循环应变来降低其自由能的结果。此外，我们研究了循环应变规避机制的动力学，并证明它主要是由于细胞的刚体旋转而出现的，而不是通过涉及细胞应变的轨迹。我们的结果为细胞形态和应力纤维的耦合动力学提供了清晰的物理见解，这最终导致了循环应变组织中的细胞组织。
