| First Author | Bachmann M | Year | 2020 |
| Journal | J Cell Sci | Volume | 133 |
| Issue | 9 | PubMed ID | 32193334 |
| Mgi Jnum | J:295987 | Mgi Id | MGI:6441269 |
| Doi | 10.1242/jcs.242404 | Citation | Bachmann M, et al. (2020) Induction of ligand promiscuity of alphaVbeta3 integrin by mechanical force. J Cell Sci 133(9):jcs242404 |
| abstractText | alphaVbeta3 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 alphaVbeta3 integrin-mediated binding to different ligands on the subcellular scale. Super-resolution imaging revealed that alphaVbeta3 integrin preferred binding to Vn under various conditions. In contrast, binding to Fn required higher mechanical load on alphaVbeta3 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 alphaVbeta3-Fn binding. Thus, force-dependent conformational changes in alphaVbeta3 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. |
