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Matrix Biol. 2017 Jul;60-61:70-85. doi: 10.1016/j.matbio.2016.07.002. Epub 2016 Jul 14.

Force regulated conformational change of integrin αVβ3.

Author information

1
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.
2
Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
3
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.
4
Yale Cardiovascular Research Center, Departments of Internal Medicine (Section of Cardiovascular Medicine), Cell Biology and Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
5
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.

Abstract

Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has 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 αVβ3 integrins 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 αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single-molecule level.

KEYWORDS:

Binding kinetics; Biomechanics; Force regulation; Integrin conformational change; Integrin α(V)β(3)

PMID:
27423389
PMCID:
PMC5237428
DOI:
10.1016/j.matbio.2016.07.002
[Indexed for MEDLINE]
Free PMC Article

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