Biophysics of selectin-mediated cell adhesion

Selectins (L-, P- and E-selectin) are Ca²⁺-dependent transmembrane glycoproteins presented on the surface of circulating leukocytes, activated platelets, and endothelial cells at sites of inflammation/infection. Selectins bind primarily to sialofucosylated glycoproteins and glycolipids (E-selectin only) on apposing cells, and mediate loose adhesive interactions pertinent to inflammatory disorders and blood-borne metastasis. The fast association and dissociation rates of selectin-ligand bonds coupled to their remarkably high tensile strengths enable them to initiate cell tethering and rolling interactions under physiological flow conditions. This chapter reviews mathematical models and experimental methodologies to highlight the biophysics of selectin-mediated cell adhesion. It summarizes experimental observations on selectin-ligand bond association and dissociation disclosed by different biophysical techniques including micropipette aspiration assays, atomic force microscopy and flow-based adhesion assays. The catch-to-slip selectin-ligand bond dissociation and its contribution to the shear threshold phenomenon are discussed. Understanding the kinetic and micromechanical properties of selectin-ligand bonds mediating cell adhesion pertinent to inflammation and hematogenous metastasis may provide guidelines for developing promising therapies and/or diagnostic tools to combat these disorders.