EFFECTS OF COLLAGENASE-CLEAVAGE OF TYPE-I COLLAGEN ON ALPHA(2)BETA(1)-INTEGRIN-MEDIATED CELL-ADHESION

In this paper we show that collagenase-3 cleavage of type I collagen h as a marked effect on alpha(2) beta(1) integrin-mediated interactions with the collagen fragments generated. Isolated alpha(2) beta(1) integ rin and alpha(2) integrin A-domain were found to bind to both native c ollagen and native 3/4 fragment and, to a lesser degree, native 1/4 fr agment. Whole integrin and integrin A-domain binding were lost after h eat denaturation of the collagen fragments. At physiological temperatu re, cell adhesion to triple-helical 3/4 fragment via alpha(2) beta(1) integrin was still possible; however, no alpha(2) beta(1) integrin-med iated adhesion to the 1/4 fragment was observed. Unwinding of the coll agen fragment triple helices by heating to physiological temperatures prior to adsorption to plastic tissue culture plates resulted in total abrogation of HT1080 cell attachment to either fragment. These result s provide significant evidence in support of a role for matrix-metallo proteinase cleavage of the extracellular matrix in modifying cell-matr ix interactions.