细胞粘附蛋白将不同细胞结合在一起构成生物组织与器官，它们不仅具有交联的功能，也是细胞感知环境力学信号的传感器。单分子操纵技术可以精确地控制作用在单个蛋白分子上的拉力并以纳米精度测量蛋白的伸长变化，是研究细胞粘附蛋白的力学响应的最适合的实验手段。本项目将利用磁镊单分子操纵技术，模拟细胞在受到外力拉伸时的生物过程，对单个细胞粘附蛋白进行力学拉伸，来研究拉力依赖的蛋白构象变化和相互作用的变化。本项目的主要研究目标和研究内容包括：（1）研究细胞粘附蛋白β-catenin，P120ctn的稳定性、拉力导致的构象转变和折叠/去折叠的动力学过程；（2）研究细胞粘附蛋白E-cadherin的胞内结构域与β-catenin蛋白之间相互作用与所受拉力的依赖关系；（3）研究固有无序蛋白的熵弹性和结合诱导的构象转变过程。本项目的意义在于通过在单个蛋白分子水平上的精确力学操纵和测量来揭示细胞力学传感的分子机制。

Cells attach to each other to form tissues and organs through cell-adhesion proteins. Cell-adhesion proteins not only function as cross-linkers, but also work as force sensors to help cell sense their surrounding mechanical environment. Single molecular manipulation techniques can control stretching force on single protein molecule precisely, and measure the extension of single protein with high spatial resolution of nanometers, which makes such methods the most proper experimental techniques to study the force response of cell-adhesion proteins. In this proposal, we will simulate the biological process when cell is stretched by mechanical force by using single molecular manipulation technique magnetic tweezers. Single purified cell-adhesion protein will be stretched and the force-dependent conformation transition and interaction will be studied. The main aims and contents of the proposed project include: (1) study the stability, force-dependent conformation transition, and folding/unfolding dynamics of cell-adhesion proteins β-catenin and P120ctn; (2) study force-dependent interaction between intracellular domain of E-cadherin and β-catenin; (3) study the entropic elasticity of intrinsic disordered protein and its conformation transition induced by protein-binding. This project will disclose the molecular mechanism of mechanical sensing function of cells through quantitative single molecular force manipulation and measurement of cell-adhesion proteins.