细胞对物理力量做出响应的能力对于发育和生理来说都是根本性的,包括血液、细胞粘附和迁移的调控。难以对活体细胞中的分子力进行测量的难度限制了对此现象的研究。
现在,Grashoff等人报告,他们开发出一个基因编码的荧光张力感应模块,该模块能够在活体中测量穿过特定蛋白的机械力。这种传感器在“粘着斑蛋白”上进行了测试。该蛋白是一种膜-细胞骨架蛋白,它被吸引到粘着斑(焦点粘连)上,并将细胞粘附分子(整合素)与肌动蛋白细丝相连。
这些数据揭示了一种调控机制,在其中,“粘着斑蛋白”承受力的能力决定粘着斑在力的作用下是整合还是分解。这种新型生物传感器应能应用于力传导中所涉及的其他蛋白。(生物谷Bioon.net)
生物谷推荐原文出处:
Nature doi:10.1038/nature09198
Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics
Carsten Grashoff,Brenton D. Hoffman,Michael D. Brenner,Ruobo Zhou,Maddy Parsons,Michael T. Yang,Mark A. McLean,Stephen G. Sligar,Christopher S. Chen,Taekjip Ha& Martin A. Schwartz
Mechanical forces are central to developmental, physiological and pathological processes1. However, limited understanding of force transmission within sub-cellular structures is a major obstacle to unravelling molecular mechanisms. Here we describe the development of a calibrated biosensor that measures forces across specific proteins in cells with piconewton (pN) sensitivity, as demonstrated by single molecule fluorescence force spectroscopy2. The method is applied to vinculin, a protein that connects integrins to actin filaments and whose recruitment to focal adhesions (FAs) is force-dependent3. We show that tension across vinculin in stable FAs is ~2.5?pN and that vinculin recruitment to FAs and force transmission across vinculin are regulated separately. Highest tension across vinculin is associated with adhesion assembly and enlargement. Conversely, vinculin is under low force in disassembling or sliding FAs at the trailing edge of migrating cells. Furthermore, vinculin is required for stabilizing adhesions under force. Together, these data reveal that FA stabilization under force requires both vinculin recruitment and force transmission, and that, surprisingly, these processes can be controlled independently.