期刊
JOURNAL OF THE ROYAL SOCIETY INTERFACE
卷 11, 期 99, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rsif.2014.0734
关键词
focal adhesion; mechanosensor; mechanotransduction; substrate stiffness; talin; vinculin
资金
- Seed Fund from the Mechanobiology Institute at the National University of Singapore
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [15086207, 16GS0308, 21247021, 24247028]
- Grants-in-Aid for Scientific Research [21247021, 15086207] Funding Source: KAKEN
At cell-substrate adhesion sites, the linkage between actin filaments and integrin is regulated by mechanical stiffness of the substrate. Of potential molecular regulators, the linker proteins talin and vinculin are of particular interest because mechanical extension of talin induces vinculin binding with talin, which reinforces the actin-integrin linkage. For understanding the molecular and biophysical mechanism of rigidity sensing at cell-substrate adhesion sites, we constructed a simple physical model to examine a role of talin extension in the stiffness-dependent regulation of actin-integrin linkage. We show that talin molecules linking between retrograding actin filaments and substrate-bound integrin are extended in a manner dependent on substrate stiffness. The model predicts that, in adhesion complexes containing approximate to 30 talin links, talin is extended enough for vinculin binding when the substrate is stiffer than 1 kPa. The lifetime of talin links needs to be 2-5 s to achieve an appropriate response of talin extension against substrate stiffness. Furthermore, changes in actin velocity drastically shift the range of substrate stiffness that induces talin-vinculin binding. Our results suggest that talin extension is a key step in sensing and responding to substrate stiffness at cell adhesion sites.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据