Selective binding and lateral clustering of ?5?1 and ?v?3 integrins: Unraveling the spatial requirements for cell spreading and focal adhesion assembly.

ABSTRACT: Coordination of the specific functions of ?5?1 and ?v?3 integrins is crucial for the precise regulation of cell adhesion, spreading and migration, yet the contribution of differential integrin-specific crosstalk to these processes remains unclear. To determine the specific functions of ?v?3 and ?5?1 integrins, we used nanoarrays of gold particles presenting immobilized, integrin-selective peptidomimetic ligands. Integrin binding to the peptidomimetics is highly selective, and cells can spread on both ligands. However, spreading is faster and the projected cell area is greater on ?5?1 ligand; both depend on ligand spacing. Quantitative analysis of adhesion plaques shows that focal adhesion size is increased in cells adhering to ?v?3 ligand at 30 and 60 nm spacings. Analysis of ?v?3 and ?5?1 integrin clusters indicates that fibrillar adhesions are more prominent in cells adhering to ?5?1 ligand, while clusters are mostly localized at the cell margins in cells adhering to ?v?3 ligand. ?v?3 integrin clusters are more pronounced on ?v?3 ligand, though they can also be detected in cells adhering to ?5?1 ligand. Furthermore, ?5?1 integrin clusters are present in cells adhering to ?5?1 ligand, and often colocalize with ?v?3 clusters. Taken together, these findings indicate that the activation of ?v?3 integrin by ligand binding is dispensable for initial adhesion and spreading, but essential to formation of stable focal adhesions.

SUBMITTER: Schaufler V 

PROVIDER: S-EPMC5079398 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature