Circulating lymphocytes are floating in a sea of fibrinogen, fibronectin, and vitronectin, all potential binding partners for integrins on the cell surface. Somehow adhesion is turned off until these matrix proteins leak out of the blood and into tissues at sites of inflammation and injury. Only then does cleavage by pro-coagulants induce polymerization, and the resulting polyvalency, according to Stupack et al. (page ), results in integrin-mediated adhesion. “It gives the cell a middle ground, they can explore a situation without prior activation,” says senior author David Cheresh.
Polymerization does not simply expose new binding sites for the lymphocytes. Rather it creates a structure with the correct spacing of binding sites. The clustered integrins then form functional signaling complexes and activate the cell.
Spacing rather than average density is the key. Stupack et al. use as their model a pentavalent coat protein of adenovirus, which has presumably evolved for...
