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标题：A model for cyclic mechanical reinforcement
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作者：Zhenhai Li ; Fang Kong ; Cheng Zhu 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep35954
语种：English
出版社：Springer Nature
摘要：Mechanical force regulates a broad range of molecular interactions in biology. Three types of counterintuitive mechanical regulation of receptor-ligand dissociation have been described. Catch bonds are strengthened by constant forces, as opposed to slip bonds that are weakened by constant forces. The phenomenon that bonds become stronger with prior application of cyclic forces is termed cyclic mechanical reinforcement (CMR). Slip and catch bonds have respectively been explained by two-state models. However, they assume fast equilibration between internal states and hence are inadequate for CMR. Here we propose a three-state model for CMR where both loading and unloading regulate the transition of bonds among the short-lived, intermediate, and long-lived state. Cyclic forces favor bonds in the long-lived state, hence greatly prolonging their lifetimes. The three-state model explains the force history effect and agrees with the experimental CMR effect of integrin α5β1-fibronectin interaction. This model helps decipher the distinctive ways by which molecular bonds are mechanically strengthened: catch bonds by constant forces and CMR by cyclic forces. The different types of mechanical regulation may enable the cell to fine tune its mechanotransduction via membrane receptors.