title: Cyclic mechanical reinforcement of integrin-ligand interactions.
abstract: Cells regulate adhesion in response to internally generated and externally applied forces. Integrins connect the extracellular matrix to the cytoskeleton and provide cells with mechanical anchorages and signaling platforms. Here we show that cyclic forces applied to a fibronectin-integrin α5β1 bond switch the bond from a short-lived state with 1 s lifetime to a long-lived state with 100 s lifetime. We term this phenomenon "cyclic mechanical reinforcement," as the bond strength remembers the history of force application and accumulates over repeated cycles, but does not require force to be sustained. Cyclic mechanical reinforcement strengthens the fibronectin-integrin α5β1 bond through the RGD binding site of the ligand with the synergy binding site greatly facilitating the process. A flexible integrin hybrid domain is also important for cyclic mechanical reinforcement. Our results reveal a mechanical regulation of receptor-ligand interactions and identify a molecular mechanism for cell adhesion strengthening by cyclic forces.
authors: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Fang
authors: F
authors: Kong
authors: Zhenhai
authors: Z
authors: Li
authors: William M
authors: WM
authors: Parks
authors: David W
authors: DW
authors: Dumbauld
authors: Andrés J
authors: AJ
authors: García
authors: A Paul
authors: AP
authors: Mould
authors: Martin J
authors: MJ
authors: Humphries
authors: Cheng
authors: C
authors: Zhu
mesh_terms: D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D005353:Fibronectins / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry* / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000502:physiology; D019169:Jurkat Cells; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D011137:Polystyrenes / Q000737:chemistry; D011485:Protein Binding
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D008567:Membranes, Artificial; D010446:Peptide Fragments; D011137:Polystyrenes; D018799:Intercellular Adhesion Molecule-1