細(xì)胞對(duì)物理力量做出響應(yīng)的能力對(duì)于發(fā)育和生理來(lái)說(shuō)都是根本性的,,包括血液、細(xì)胞粘附和遷移的調(diào)控,。難以對(duì)活體細(xì)胞中的分子力進(jìn)行測(cè)量的難度限制了對(duì)此現(xiàn)象的研究,。
現(xiàn)在,Grashoff等人報(bào)告,,他們開(kāi)發(fā)出一個(gè)基因編碼的熒光張力感應(yīng)模塊,,該模塊能夠在活體中測(cè)量穿過(guò)特定蛋白的機(jī)械力。這種傳感器在“粘著斑蛋白”上進(jìn)行了測(cè)試,。該蛋白是一種膜-細(xì)胞骨架蛋白,,它被吸引到粘著斑(焦點(diǎn)粘連)上,并將細(xì)胞粘附分子(整合素)與肌動(dòng)蛋白細(xì)絲相連,。
這些數(shù)據(jù)揭示了一種調(diào)控機(jī)制,,在其中,“粘著斑蛋白”承受力的能力決定粘著斑在力的作用下是整合還是分解。這種新型生物傳感器應(yīng)能應(yīng)用于力傳導(dǎo)中所涉及的其他蛋白,。(生物谷Bioon.net)
生物谷推薦原文出處:
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.