TY - JOUR
T1 - Force regulated conformational change of integrin αVβ3
AU - Chen, Yunfeng
AU - Lee, Hyunjung
AU - Tong, Haibin
AU - Schwartz, Martin
AU - Zhu, Cheng
N1 - Funding Information:
This work was supported by National Institutes of Health grant R01AI044902 (CZ), Army Research Office DOD W911NF-16-1-0257 (CZ), and the Army Research Office MURI W911NF-14-0403 (MS).
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - Binding kinetics
KW - Biomechanics
KW - Force regulation
KW - Integrin conformational change
KW - Integrin αβ
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U2 - 10.1016/j.matbio.2016.07.002
DO - 10.1016/j.matbio.2016.07.002
M3 - Article
C2 - 27423389
AN - SCOPUS:84979573607
SN - 0945-053X
VL - 60-61
SP - 70
EP - 85
JO - Collagen and Related Research
JF - Collagen and Related Research
ER -