title: Force regulated conformational change of integrin αVβ3.
abstract: Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3acts as a molecular machine and how its physiological function and molecular structure are coupled at the single-molecule level.
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Yale Cardiovascular Research Center, Departments of Internal Medicine (Section of Cardiovascular Medicine), Cell Biology and Biomedical Engineering, Yale University, New Haven, CT 06511, USA; Current address: Life Science Research Center, Beihua University, Jilin 132013, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Tong
authors.affiliation: Yale Cardiovascular Research Center, Departments of Internal Medicine (Section of Cardiovascular Medicine), Cell Biology and Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA; Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: cheng.zhu@bme.gatech.edu.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019921:Biotinylation; D002448:Cell Adhesion; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D004912:Erythrocytes / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D005353:Fibronectins / Q000737:chemistry*; D015870:Gene Expression; D005898:Glass / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction; D000072760:Single Molecule Imaging / Q000379:methods
chemical_list: D005353:Fibronectins; D039302:Integrin alphaVbeta3; D015335:Molecular Probes; C501364:fibronectin type III like peptide, human
keywords: Binding kinetics; Biomechanics; Force regulation; Integrin conformational change; Integrin α(V)β(3)