Schematic model showing the binding of EVs to the recipient cell PM. (A) Integrin heterodimers in EVs, α6β1/α6β4 and α2β1, can bind to laminin and collagen type I, respectively, but integrin heterodimers in EVs, such as α5β1, bind only weakly to fibronectin. CD151 enhances the binding of integrins α6β1 and α6β4 in sEVs to laminin. Cholesterol in sEVs suppresses laminin binding through a CD151-dependent mechanism. (B) Because Ser425 of talin-1 is hardly phosphorylated in EVs, talin-1 is inactive and is not involved in promoting the ECM-binding activity of integrin heterodimers. Kindlin-2 is also not involved in the activation of integrin heterodimers in EVs.