Stability of adhesion clusters and cell reorientation under lateral cyclic tension

Stability of adhesion clusters and cell reorientation under lateral cyclic tension
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横向循环张力下粘附簇的稳定性和细胞重新定向

DOI:
10.1529/biophysj.108.131342
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发表时间:
2008-10-15
影响因子:
3.4
通讯作者:
Dai, Lanhong
Dai, Lanhong
中科院分区:
生物学3区
文献类型:
--
作者:
Kong, Dong;Ji, Baohua;Dai, Lanhong

文献摘要

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这项工作是由实验观察所推动的,即拉伸基底上的细胞对静态和动态载荷表现出不同的反应。通过将粘着斑视为粘着簇,在分子水平上开发了一种能够考虑应力纤维、粘着键和基底力学的粘着斑模型。通过在基底上施加循环外部应变来研究该簇在动态载荷下的稳定性。我们表明存在一个外部应变振幅的阈值,超过该阈值,粘着簇会迅速瓦解。此外,我们的结果表明,粘着簇在高频载荷下容易失去稳定性,因为由于基底的高速变形,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,这导致键发生显著变形。此外,我们发现应力纤维的刚度和松弛时间在粘着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着键的动力学(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。
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.