Sun Zhiqi, Guo Shengzhen S, Fässler Reinhard
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
J Cell Biol. 2016 Nov 21;215(4):445-456. doi: 10.1083/jcb.201609037. Epub 2016 Nov 8.
Cells can detect and react to the biophysical properties of the extracellular environment through integrin-based adhesion sites and adapt to the extracellular milieu in a process called mechanotransduction. At these adhesion sites, integrins connect the extracellular matrix (ECM) with the F-actin cytoskeleton and transduce mechanical forces generated by the actin retrograde flow and myosin II to the ECM through mechanosensitive focal adhesion proteins that are collectively termed the "molecular clutch." The transmission of forces across integrin-based adhesions establishes a mechanical reciprocity between the viscoelasticity of the ECM and the cellular tension. During mechanotransduction, force allosterically alters the functions of mechanosensitive proteins within adhesions to elicit biochemical signals that regulate both rapid responses in cellular mechanics and long-term changes in gene expression. Integrin-mediated mechanotransduction plays important roles in development and tissue homeostasis, and its dysregulation is often associated with diseases.
细胞可通过基于整合素的黏附位点检测细胞外环境的生物物理特性并做出反应,在一个称为机械转导的过程中适应细胞外环境。在这些黏附位点,整合素将细胞外基质(ECM)与F-肌动蛋白细胞骨架相连,并通过统称为“分子离合器”的机械敏感黏着斑蛋白,将由肌动蛋白逆行流和肌球蛋白II产生的机械力传递至ECM。跨基于整合素的黏附位点的力传递在ECM的黏弹性和细胞张力之间建立了机械互易性。在机械转导过程中,力通过变构改变黏附位点内机械敏感蛋白的功能,以引发调节细胞力学快速反应和基因表达长期变化的生化信号。整合素介导的机械转导在发育和组织稳态中发挥重要作用,其失调常与疾病相关。