Li Zhenhai, Kong Fang, Zhu Cheng
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Sci Rep. 2016 Oct 27;6:35954. doi: 10.1038/srep35954.
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 αβ-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.
机械力调节生物学中广泛的分子相互作用。已经描述了三种违反直觉的受体 - 配体解离的机械调节类型。与因恒定力而减弱的滑动键相反，捕获键因恒定力而增强。键在先前施加循环力后变强的现象称为循环机械增强（CMR）。滑动键和捕获键分别由双态模型解释。然而，它们假设内部状态之间快速平衡，因此不足以解释CMR。在这里，我们提出了一个用于CMR的三态模型，其中加载和卸载都调节键在短寿命、中间寿命和长寿命状态之间的转变。循环力有利于键处于长寿命状态，从而大大延长其寿命。三态模型解释了力历史效应，并与整合素αβ-纤连蛋白相互作用的实验CMR效应一致。该模型有助于解读分子键通过机械方式增强的独特方式：通过恒定力增强捕获键，通过循环力增强CMR。不同类型的机械调节可能使细胞能够通过膜受体微调其机械转导。
