Molecular properties of fibrin-based matrices for promotion of angiogenesis in vitro

The molecular properties of fibrin-based matrices, such as fibrillar struct ure and covalent modifications with adhesion domains, influence the angioge nic behavior of human umbilical vein endothelial cells (HUVECs) in vitro. T he fibrillar structure of fibrin-based matrices was influenced by pH but no t by covalent incorporation of exogenous adhesion domains. Native fibrin-ba sed matrices polymerized at pH 10 formed organized and longitudinally orien ted fibrin fibrils, which provided a good angiogenic substrate for endothel ial cells. Furthermore, upon covalent incorporation of the model ligand L1I g6, which binds to the integrin most prominently expressed on the surface o f angiogenic endothelial cells, alphav beta3, these matrices became angioge nesis-promoting when polymerized at physiological pH. The amount of incorpo ration of L1Ig6 into the matrices depended on the fibrinogen concentration on all three fibrin chains. Soluble forms of L1Ig6 diffused rapidly out of the matrix. Most important, L1Ig6-modified matrices were very specific in i nducing the angiogenic phenotype of HUVECs, whereas control cells did not d ifferentiate on these matrices. Our results indicate that artificial extrac ellular matrices can influence cell behavior in two ways. One way is based on the three-dimensional fibril structure of the matrix molecules themselve s, and the other is due to providing specific binding sites for direct cell -matrix interactions that lead to the activation of second-messenger cascad es and thus promoting angiogenic differentiation. (C) 2001 Academic Press.