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Induction of ligand promiscuity of αVβ3 integrin by mechanical force

Schäfer, Markus
Mykuliak, Vasyl V
Heiser, Lia
Weißenbruch, Kai
Krübel, Sarah
Franz, Clemens M
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Published in Journal of Cell Science. 2020, vol. 133, no. 9, jcs242404
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 AdhesionExtracellular Matrix ProteinsFibronectins/geneticsIntegrin alphaVbeta3/geneticsIntegrinsLigandsMechanical PhenomenaVitronectin/genetics
PMID: 32193334
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Research group Migration cellulaire (645)
FNS: 31003A_166384
FNS: 310030L_170112/1
(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 https://archive-ouverte.unige.ch/unige:153885

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Deposited on : 2021-08-16

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