Induction of ligand promiscuity of αVβ3 integrin by mechanical force.

Journal of cell science (2020-03-21)
Michael Bachmann, Markus Schäfer, Vasyl V Mykuliak, Marta Ripamonti, Lia Heiser, Kai Weißenbruch, Sarah Krübel, Clemens M Franz, Vesa P Hytönen, Bernhard Wehrle-Haller, Martin Bastmeyer

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.

Product Number
Product Description

Anti-Fibronectin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Acrylic acid N-hydroxysuccinimide ester, ≥90%
Vitronectin human, recombinant, expressed in HEK 293 cells, ≥95% (SDS-PAGE), ≥95% (HPLC), suitable for cell culture
Monoclonal Anti-Talin antibody produced in mouse, clone 8d4, ascites fluid
Vitronectin from human plasma, lyophilized powder, BioReagent, suitable for cell culture
HEPBS, ≥99% (titration)
Osteopontin from bovine milk, lyophilized powder
Monoclonal Anti-Vitronectin antibody produced in mouse, clone VIT-2, ascites fluid

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon


Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.