力敏感受体介导细胞功能调控的力学生物学研究

细胞膜是细胞与外部环境进行物质与能量交换的界面,是调节细胞正常生命活动的重要结构基础.细胞膜上力敏感受体可通过力学作用方式参与并影响细胞的力信号转导等功能.整合素和钙黏素是细胞膜上典型的力敏感受体,可介导细胞与细胞周围基质或邻近细胞发生力学作用,并将力学刺激信号转导为生化信号,进而激活细胞内一系列应答反应,最终影响细胞生长、分化、增殖、凋亡和迁移等功能.力敏感受体介导细胞功能调控研究已成为探索细胞主动响应外界复杂力学微环境的力学生物学机制的关键,为进一步深入认识生理和病理状态下细胞功能变化规律,为揭示疾病的发生、发展机制提供重要的力学生物学理论与实验依据.本文总结了力敏感受体介导细胞功能调控的国内外研究进展;介绍了黏附界面处典型力敏感受体的结构和功能;总结了这些力敏感受体参与的细胞力信号感知与响应的数理模型;概述了细胞通过力敏感受体进行力学信号转导的过程;介绍了黏附介导细胞功能调控的力学生物学过程和机制;简述了体外构建模拟细胞力学微环境中细胞-细胞外基质和细胞-细胞力学相互作用的技术;指出了力敏感受体介导细胞功能调控的力学生物学研究发展趋势和未来方向.

Cellular mechanobiology: Mediated by force-sensitive adhesion receptors

As the interface between cells and their external environment for materials and energy exchange, the cell membrane is an important structure that regulates cellular activities. Representative transmembrane force-sensitive receptors, such as integrins and cadherins, are found to play key roles in mediating cellular interactions with the ECM or adjacent cells. These interactions will then transduce mechanical stimuli into biochemical signals, which in turn activate a series of intracellular signaling cascade, and ultimately affect cell growth, differentiation, proliferation, migration and apoptosis etc. The investigation of cellular mechanobiology regulated by force-sensitive adhesion receptors has thus become the key to explore the mechanobiological mechanisms of cellular actively in response to complex mechanical microenvironments. This provides valuable theoretical and experimental basis for further understanding of the changes in cell functions under physiological and pathological conditions, as well as for revealing the mechanism of disease development. This review summarizes the cutting-edge progresses in cellular mechanobiology regulated force-sensitive adhesion receptors. This review begins by introducing the structure and function of force-sensitive receptors at the adhesion interface, and followed by elaborating systematic mathematical models of how cells sense and respond to mechanical signals mediated by these receptors. It also outlines the processes of mechanical signal transduction through force-sensitive receptors, and the mechanobiological mechanism of adhesion-mediated changes in cell functions. In addition, the techniques for constructing of in vitro mechanical microenvironment that mimic cell-ECM (via integrin ligation) and cell-cell (via cadherin ligation) interactions are described. Finally, we identify the future directions of mechanobiology in terms of force-sensitive receptors regulated cell functions.