RGDX1X2 motif regulates integrin αvβ5 binding for pluripotent stem cell adhesion

Abstract The arginine‐glycine‐aspartic acid (RGD) motif is a cell adhesion sequence that binds to integrins. Some RGD‐containing peptides promote adhesion of both embryonic stem cells and induced pluripotent stem cells (iPSCs); however, not all such RGD‐containing peptides are active. In this study, we elucidated the role of RGD‐neighboring sequences on iPSC adhesion using diverse synthetic peptides and recombinant proteins. Our results indicate that iPSC adhesion requires RGDX 1 X 2 sequences, such as RGDVF and RGDNY, and that the X 1 X 2 residues are essential for the adhesion via integrin αvβ5 but not αvβ3. iPSCs express integrin αvβ5 but not αvβ3; therefore, iPSC adhesion requires the RGDX 1 X 2 ‐containing sequences. The importance of the X 1 X 2 residues was confirmed with both HeLa and A549 cells, which express integrin αvβ5 but not αvβ3. Analysis of RGD‐neighboring sequences provides important insights into ligand‐binding specificity of integrins. Identification of integrin αvβ5‐binding motifs is potentially useful in drug development, drug delivery, cell culture, and tissue engineering.