title: Observing force-regulated conformational changes and ligand dissociation from a single integrin on cells.
abstract: As adhesion molecules, integrins connect a cell to its environment and transduce signals across the membrane. Their different functional states correspond to distinct conformations. Using a biomembrane force probe, we observed real-time reversible switches between bent and extended conformations of a single integrin, α(L)β(2), on the surface of a living cell by measuring its nanometer-scale headpiece displacements, bending and unbending frequencies, and molecular stiffness changes. We determined the stabilities of these conformations, their dynamic equilibrium, speeds and rates of conformational changes, and the impact of divalent cations and tensile forces. We quantified how initial and subsequent conformations of α(L)β(2) regulate the force-dependent kinetics of dissociation from intercellular adhesion molecule 1. Our findings provide new insights into how integrins function as nanomachines to precisely control cell adhesion and signaling.
authors.affiliation: Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Jizhong
authors.initials: J
authors.lastname: Lou
authors.forename: Evan A
authors.initials: EA
authors.lastname: Evans
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002412:Cations / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004912:Erythrocytes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007700:Kinetics; D007963:Leukocytes, Mononuclear; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D002412:Cations; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1