Mechanism of avb3 integrin recruitment to a5b1 integrin based focal adhesions

CAROLINA DIAZ; DIMITRIS MISSIRLIS; JOACHIM SPATZ

Sant Feliu de Guixols-Catalonia

Conferencia; Biological Surfaces and Interfaces; 2017

The Federation of European Biochemical Societies (FEBS) and MIME Research Group

The major fibronectin (FN) binding integrins α5β1 and αvβ3 exhibit co-operativity during cell adhesion, migration and mechanosensing, through mechanisms that are not yet fully understood. Exploiting mechanically-tunable, nano-patterned substrates, and small molecule, peptidomimetic ligands designed to bind strongly, yet selectively, corresponding integrins, we report that focal adhesions (FAs) of endothelial cells assembled on integrin α5β1-selective substrates, rapidly recruit αvβ3 integrins. In contrast, αvβ3 integrin-based FAs do not exhibit α5β1 recruitment and clustering. Blocking integrin αvβ3 hindered FA assembly and cell spreading on α5β1-selective substrates, indicating a mechanism dependent on extracellular binding and highlighting the requirement of αvβ3 engagement for efficient adhesion. Recruitment of αvβ3 integrins occurred independent of substrate mechanical properties, above a threshold stiffness supporting FA formation. Mechanistic studies revealed the need for the presence of soluble αvβ3 ligands to allow recruitment, and excluded exogenous, or endogenous, FN as the responsible ligand. Our findings highlight a novel mechanism of integrin co-operation and the critical role for αvβ3 integrins in promoting cell adhesion.