IntegrinBinding

Integrin binding refers to the interaction between integrins, a family of transmembrane adhesion receptors, and their ligands in the extracellular matrix or on other cells. These interactions mediate cell adhesion, migration, and bidirectional signaling that regulates cellular behavior.

Integrins are heterodimers composed of α and β subunits. Ligand binding occurs at the β-subunit or the I-domain in certain α-subunits; binding is modulated by divalent cations such as Ca2+, Mg2+, and sometimes Mn2+, and by conformational changes that switch integrins between inactive bent and active extended forms. Activation can be triggered by inside-out signals from the cytoskeleton via adaptors such as talin and kindlin, or by extracellular cues.

Common extracellular matrix ligands include fibronectin, collagen, laminin, and vitronectin; many ligands present the Arg-Gly-Asp (RGD) sequence that binds to several integrin types. Other ligands include osteopontin, laminin-derived peptides, and cell-surface counter-receptors. Binding affinity and specificity vary among αβ combinations.

Upon binding, integrins cluster into focal adhesions and connect to the actin cytoskeleton, enabling force transmission and signaling through kinases such as FAK and Src, and pathways including PI3K/AKT and MAPK. Outside-in signaling regulates survival, proliferation, and differentiation; inside-out signaling modulates affinity and avidity.

Biological roles are broad, including development, hemostasis, immune cell trafficking, wound healing, and angiogenesis. Dysregulation of integrin binding is implicated in cancer metastasis, fibrosis, and inflammatory diseases. Therapeutic strategies target integrin binding to inhibit thrombosis or tumor progression, though specificity and side effects remain challenges.