The effect of advanced glycation end-product formation upon cell-matrix interactions

The formation of advanced glycation end-products plays a central role in th e progressive deterioration of tissues with age, a process that is accelera ted in diabetes. Collagen in addition to providing structure and tensile st rength to tissues also provides a dynamic matrix for cells to interact with , and due to its long-lived nature is particularly susceptible to modificat ion with age and disease. We have recently identified methylglyoxal as a ke y intermediate in this process, reacting predominantly with arginine residu es to form imidazolone compounds. We therefore postulated that modification of RGD sequences in collagen with methylglyoxal would interfere with cruci al cell-matrix interactions. To investigate this concept we studied the int eraction of two cell lines, MG63 and HT1080, with collagen modified to vary ing degrees with respect to arginine. Adhesion and subsequent spreading of both cell lines was significantly decreased by minimal methylglyoxal modifi cation leading to the conclusion that such modification of collagen severel y inhibits cell matrix interactions, most likely via the loss of specific a rginine residues involved in integrin mediated cell attachment. This is the first demonstration that methylglyoxal modification of collagen can affect cell-matrix interactions and introduces a possible mechanism by which some of the deleterious changes in tissues with age and disease are occurring. (C) 1999 Elsevier Science Ltd. All rights reserved.