来自微环境的机械线索在许多生理和病理过程中起着调节作用,如干细胞分化和癌细胞转移。实验表明,粘附在顺应性基底上的细胞可以随着基底中外部施加的应变而改变取向。通过考虑肌动蛋白聚合,肌动蛋白逆行流动,和整合素结合动力学,在这里,我们开发了一个基于机制的张力整体模型,以研究极化细胞在双轴拉伸下在顺应性基底上的取向。我们表明,细胞可以通过沿其极化方向产生不同的牵引力水平来主动调节其机械状态。在静态或超低频循环拉伸下,拉伸较软的基材会导致牵引力的更大增加,并导致细胞排列的分布变窄。与静态载荷相比,高频循环负载对刚性基板上的细胞重新定向有更显著的影响。此外,在静态和循环拉伸下,细胞角分布的宽度与拉伸幅度成反比。我们的结果与广泛的实验观察结果一致,并提供对细胞机械传感系统功能的基本见解。
Mechanical cues from the microenvironments play a regulating role in many physiological and pathological processes, such as stem cell differentiation and cancer cell metastasis. Experiments showed that cells adhered on a compliant substrate may change orientation with an externally applied strain in the substrate. By accounting for actin polymerization, actin retrograde flow, and integrin binding dynamics, here we develop a mechanism-based tensegrity model to
study the orientations of polarized cells on a compliant substrate under biaxial stretches. We show that the cell can actively regulate its mechanical state by generating different traction force levels along its polarized direction. Under static or ultralow-frequency cyclic stretches, stretching a softer substrate leads to a higher increase in the traction force and induces a narrower distribution of cell alignment. Compared to static loadings, high-frequency cyclic loadings have a more significant influence on cell reorientation on a stiff substrate. In addition, the width of the cellular angular distribution scales inversely with the stretch amplitude under both static and cyclic stretches. Our results are in agreement with a wide range of experimental observations, and provide fundamental insights into the functioning of cellular mechanosensing systems.