en
Scientific article
English

Induction of ligand promiscuity of αVβ3 integrin by mechanical force

Published inJournal of Cell Science, vol. 133, no. 9, jcs242404
Publication date2020
Abstract

αVβ3 integrin can bind to multiple extracellular matrix proteins, including vitronectin (Vn) and fibronectin (Fn), which are often presented to cells in culture as homogenous substrates. However, in tissues, cells experience highly complex and changing environments. To better understand integrin ligand selection in such complex environments, we employed binary-choice substrates of Fn and Vn to dissect αVβ3 integrin-mediated binding to different ligands on the subcellular scale. Super-resolution imaging revealed that αVβ3 integrin preferred binding to Vn under various conditions. In contrast, binding to Fn required higher mechanical load on αVβ3 integrin. Integrin mutations, structural analysis and chemical inhibition experiments indicated that the degree of hybrid domain swing-out is relevant for the selection between Fn and Vn; only a force-mediated, full hybrid domain swing-out facilitated αVβ3-Fn binding. Thus, force-dependent conformational changes in αVβ3 integrin increased the diversity of available ligands for binding and therefore enhanced the ligand promiscuity of this integrin.This article has an associated First Person interview with the first author of the paper.

Keywords
  • Cell Adhesion
  • Extracellular Matrix Proteins
  • Fibronectins/genetics
  • Integrin alphaVbeta3/genetics
  • Integrins
  • Ligands
  • Mechanical Phenomena
  • Vitronectin/genetics
Citation (ISO format)
BACHMANN, Michaël et al. Induction of ligand promiscuity of αVβ3 integrin by mechanical force. In: Journal of Cell Science, 2020, vol. 133, n° 9, p. jcs242404. doi: 10.1242/jcs.242404
Main files (1)
Article (Published version)
accessLevelRestricted
Secondary files (1)
Identifiers
ISSN of the journal0021-9533
112views
1downloads

Technical informations

Creation07/01/2021 6:45:00 PM
First validation07/01/2021 6:45:00 PM
Update time03/16/2023 1:03:08 AM
Status update03/16/2023 1:03:06 AM
Last indexation01/17/2024 1:54:38 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack