Analyzing the spatiotemporal regulation of intracellular force transduction in living cells

细胞感知和响应机械力的能力是发育、生理和病理过程的核心。然而，我们刚刚开始了解机械信息是如何被细胞转化为生化反应的，机械转导的分子机制在很大程度上是难以捉摸的。我们对分子水平上的力传导理解有限的一个原因是缺乏合适的技术来研究生理相关情况下的细胞内力传播。因此，我们最近开发了一种显微镜方法，可以可视化和测量活细胞中单个蛋白质的机械张力，具有皮牛顿灵敏度。我们将使用这项新技术来测量与整合素相关的蛋白质之间的机械张力，整合素是一类细胞表面受体，介导细胞与细胞外基质的相互作用。我们的实验将揭示对独立力转导的分子过程的基本见解，从而增加我们对细胞迁移的机械方面的理解。

The ability of cells to sense and respond to mechanical forces is central to developmental, physiological and pathological processes. However, we just begin to understand how mechanical information is translated by cells into a biochemical response, and the molecular mechanisms of mechanotransduction are largely elusive. One reason for our limited understanding of force transduction on the molecular level is the lack of suitable techniques to study intracellular force propagation under physiologically relevant situations. Therefore, we recently developed a microscopic method that allows visualization and measurement of mechanical tension across single proteins in live cells with pico-Newton sensitivity. We will use this new technique to measure mechanical tension across proteins that associate with integrins, a class of cell surface receptors which mediate the interaction of cells with the extracellular matrix. Our experiments will reveal fundamental insights into the molecular processes of integrindependent force transduction and, as a result, increase our understanding of the mechanical aspects of cell migration.