All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing
All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing
复制标题
DOI：
10.1021/acsnano.6b01658
复制
发表时间：
2016-07-01
期刊：
影响因子：
17.1
通讯作者：
Hernandez, Armando del Rio
中科院分区：
文献类型：
--
作者：
Haining, Alexander William M.;von Essen, Magdalena;Hernandez, Armando del Rio
尽管目前已经认识到机械转导在细胞信号传导中的相关性，但驱动这一过程的机制在很大程度上仍然未知。蛋白质的机械解折叠可以在细胞中触发不同的下游信号，为细胞机械转导提供机制。力诱导展开的塔林，一个突出的粘着斑蛋白，已被证明以前的一小部分杆域。在这里，使用单分子原子力显微镜（smAFM），我们表明，整个塔林杆可以展开的机械延伸，在10和40 pN之间的力的生理范围。我们还表明，通过smAFM和转向分子动力学的组合，塔林杆内的不同束表现出不同层次的机械稳定性。这些结果提供了一种机制，通过这种机制，细胞内不同的力条件控制塔林杆的逐渐展开。杆亚结构域的机械展开，以及随后对塔林结合相互作用的影响，将允许对内部或外部施加的力进行微调的细胞反应。
Although the relevance of mechanotransduction in cell signaling is currently appreciated, the mechanisms that drive this process remain largely unknown. Mechanical unfolding of proteins may trigger distinct downstream signals in cells, providing a mechanism for cellular mechanotransduction. Force-induced unfolding of talin, a prominent focal adhesion protein, has been demonstrated previously for a small portion of its rod domain. Here, using single-molecule atomic force microscopy (smAFM), we show that the entire talin rod can be unfolded by mechanical extension, over a physiological range of forces between 10 and 40 pN. We also demonstrate, through a combination of smAFM and steered molecular dynamics, that the different bundles within the talin rod exhibit a distinct hierarchy of mechanical stability. These results provide a mechanism by which different force conditions within the cell control a graduated unfolding of the talin rod. Mechanical unfolding of the rod subdomains, and the subsequent effect on talin's binding interactions, would allow for a finely tuned cellular response to internally or externally applied forces.