Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by α5β1 and αvβ3 integrins

Fibrillins are the major glycoprotein components of microfibrils that form a template for tropoelastin during elastic fibrillogenesis. We have examined cell adhesion to assembled purified microfibrils, and its molecular basis. Human dermal fibroblasts exhibited Arg-Gly-Asp and cation-dependent adhesion to microfibrils and recombinant fibrillin-1 protein fragments. Strong integrin alpha(5)beta(1) interactions with fibrillin ligands were identified, but integrin alpha(v)beta(3) also contributed to cell adhesion. Fluorescence-activated cell sorting analysis confirmed the presence of abundant alpha(5)beta(1) and some alpha(v)beta(3) receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Asp-containing fibrillin-1 protein fragments induced signaling events that led to cell spreading, altered cytoskeletal organization, and enhanced extracellular fibrillin-1 deposition. Differences in cell shape when plated on fibrillin or fibronectin implied substrate-specific alpha(5)beta(1)-mediated cellular responses. An Arg-Gly-Asp-independent cell adhesion sequence was also identified within fibrillin-1. Adhesion and spreading of smooth muscle cells on fibrillin ligands was enhanced by antibody-induced beta(1) integrin activation. A375-SM melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly through alpha(v)beta(3), whereas HT1080 cells used mainly alpha(5)beta(1). This study has shown that fibrillin microfibrils mediate cell adhesion, that alpha(5)beta(1) and alpha(v)beta(3) are both important but cell-specific fibrillin-1 receptors, and that cellular interactions with fibrillin-1 influence cell behavior.