International Center for Applied Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi'an Jiaotong University, Xi'an, China.
Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
Biophys J. 2018 Feb 6;114(3):701-710. doi: 10.1016/j.bpj.2017.12.002.
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.
微环境中的力学线索在许多生理和病理过程中发挥着调节作用，例如干细胞分化和癌细胞转移。实验表明，细胞黏附在顺应性基底上时，可能会随着基底中施加的外部应变而改变方向。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，我们在这里开发了一种基于机制的张拉整体模型，以研究双轴拉伸下极化细胞在顺应性基底上的取向。我们表明，细胞可以通过在其极化方向上产生不同的牵引力水平来主动调节其力学状态。在静态或超低频率循环拉伸下，拉伸较软的基底会导致牵引力更大的增加，并诱导细胞排列的分布变窄。与静态加载相比，高频循环加载对刚性基底上细胞的重新取向有更显著的影响。此外，在静态和循环拉伸下，细胞角分布的宽度与拉伸幅度呈反比。我们的结果与广泛的实验观察结果一致，并为细胞机械感受系统的功能提供了基本的见解。
