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细胞外基质弹性介导的整合素激活和内化:一种生物力学模型。

Integrin activation and internalization mediated by extracellular matrix elasticity: a biomechanical model.

机构信息

Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.

Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.

出版信息

J Biomech. 2014 Apr 11;47(6):1479-84. doi: 10.1016/j.jbiomech.2014.01.022. Epub 2014 Jan 20.

DOI:10.1016/j.jbiomech.2014.01.022
PMID:24495754
Abstract

Cells sense and respond to the elasticity of extracellular matrix (ECM) via integrin-mediated adhesion. As a class of well-documented mechanosenors in cells, integrins switch among inactive, bound, and dissociated states, depending upon the variation of forces acting on them. However, it remains unclear how the ECM elasticity directs and affects the states of integrins and, in turn, their cellular functions. On the basis of our recent experiments, a biomechanical model is proposed to reveal the role of ECM elasticity in the state-switching of integrins. It is demonstrated that a soft ECM can increase the activation level of integrins while a stiff ECM has a tendency to prevent the dissociation and internalization of bound integrins. In addition, it is found that more stable focal adhesions can form on stiffer and thinner ECMs. The theoretical results agree well with relevant experiments and shed light on the ECM elasticity-sensing mechanisms of cells.

摘要

细胞通过整合素介导的黏附来感知和响应细胞外基质(ECM)的弹性。作为细胞中一类有充分文献记载的力感受器,整合素根据作用于其上的力的变化,在不活跃、结合和解离状态之间切换。然而,目前尚不清楚 ECM 弹性如何指导和影响整合素的状态,以及它们的细胞功能。基于我们最近的实验,提出了一个生物力学模型来揭示 ECM 弹性在整合素状态转换中的作用。结果表明,软 ECM 可以增加整合素的激活水平,而硬 ECM 则倾向于阻止结合的整合素解离和内化。此外,还发现更稳定的黏附斑可以在更硬和更薄的 ECM 上形成。理论结果与相关实验吻合较好,为细胞的 ECM 弹性感知机制提供了新的见解。

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