Kong Dong, Ji Baohua, Dai Lanhong
State Key Laboratory of Nonlinear Mechanics, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
Biophys J. 2008 Oct;95(8):4034-44. doi: 10.1529/biophysj.108.131342. Epub 2008 Jul 11.
This work is motivated by experimental observations that cells on stretched substrate exhibit different responses to static and dynamic loads. A model of focal adhesion that can consider the mechanics of stress fiber, adhesion bonds, and substrate was developed at the molecular level by treating the focal adhesion as an adhesion cluster. The stability of the cluster under dynamic load was studied by applying cyclic external strain on the substrate. We show that a threshold value of external strain amplitude exists beyond which the adhesion cluster disrupts quickly. In addition, our results show that the adhesion cluster is prone to losing stability under high-frequency loading, because the receptors and ligands cannot get enough contact time to form bonds due to the high-speed deformation of the substrate. At the same time, the viscoelastic stress fiber becomes rigid at high frequency, which leads to significant deformation of the bonds. Furthermore, we find that the stiffness and relaxation time of stress fibers play important roles in the stability of the adhesion cluster. The essence of this work is to connect the dynamics of the adhesion bonds (molecular level) with the cell's behavior during reorientation (cell level) through the mechanics of stress fiber. The predictions of the cluster model are consistent with experimental observations.
这项工作是由实验观察结果推动的,即在拉伸基质上的细胞对静态和动态载荷表现出不同的反应。通过将粘着斑视为一个粘附簇,在分子水平上建立了一个能够考虑应力纤维、粘附键和基质力学的粘着斑模型。通过在基质上施加循环外部应变,研究了动态载荷下簇的稳定性。我们表明,存在一个外部应变幅度的阈值,超过该阈值,粘附簇会迅速破坏。此外,我们的结果表明,粘附簇在高频加载下容易失去稳定性,因为由于基质的高速变形,受体和配体无法获得足够的接触时间来形成键。同时,粘弹性应力纤维在高频下变得刚性,这导致键的显著变形。此外,我们发现应力纤维的刚度和松弛时间在粘附簇的稳定性中起着重要作用。这项工作的本质是通过应力纤维的力学将粘附键的动力学(分子水平)与细胞重新定向过程中的行为(细胞水平)联系起来。簇模型的预测与实验观察结果一致。