title: A model for cyclic mechanical reinforcement.
abstract: 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.
authors: 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.|Molecular Modeling and Simulation Group, National Institutes for Quantum and Radiological Science and Technology, 8-1-7 Umemidai, Kizugawa, Kyoto 619-0215, Japan.
authors: Zhenhai
authors: Z
authors: Li
authors: Singapore MIT Alliance of Research and Technology, Infectious Disease IRG, Singapore 138602, Singapore.|Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Fang
authors: F
authors: Kong
authors: 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.|Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Cheng
authors: C
authors: Zhu
mesh_terms: D001696:Biomechanical Phenomena; D015815:Cell Adhesion Molecules / Q000502:physiology; D004734:Energy Metabolism; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D039081:Integrin alpha5beta1 / Q000737:chemistry / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D011487:Protein Conformation
chemical_list: D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039081:Integrin alpha5beta1