Molecular properties of fibrin-based matrices for promotion of angiogenesis in vitro
| Autor: | Heike Hall, Thomas Baechi, Jeffrey A. Hubbell |
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| Předmět: |
Integrins
Umbilical Veins Angiogenesis Integrin Gene Expression Neovascularization Physiologic Fibril Ligands Biochemistry Fibrin Extracellular matrix Cell Adhesion Escherichia coli Humans Cloning Molecular Cell adhesion Neural Cell Adhesion Molecules Cells Cultured Binding Sites Membrane Glycoproteins biology Chemistry Cell Biology Adhesion Hydrogen-Ion Concentration Recombinant Proteins Extracellular Matrix Protein Structure Tertiary Endothelial stem cell Phenotype Microscopy Fluorescence Immunology Biophysics biology.protein Endothelium Vascular Cardiology and Cardiovascular Medicine Gels Leukocyte L1 Antigen Complex Cell Division |
| Popis: | The molecular properties of fibrin-based matrices, such as fibrillar structure and covalent modifications with adhesion domains, influence the angiogenic behavior of human umbilical vein endothelial cells (HUVECs) in vitro. The fibrillar structure of fibrin-based matrices was influenced by pH but not by covalent incorporation of exogenous adhesion domains. Native fibrin-based matrices polymerized at pH 10 formed organized and longitudinally oriented fibrin fibrils, which provided a good angiogenic substrate for endothelial cells. Furthermore, upon covalent incorporation of the model ligand L1Ig6, which binds to the integrin most prominently expressed on the surface of angiogenic endothelial cells, alpha(v)beta3, these matrices became angiogenesis-promoting when polymerized at physiological pH. The amount of incorporation 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 inducing the angiogenic phenotype of HUVECs, whereas control cells did not differentiate on these matrices. Our results indicate that artificial extracellular matrices can influence cell behavior in two ways. One way is based on the three-dimensional fibril structure of the matrix molecules themselves, and the other is due to providing specific binding sites for direct cell-matrix interactions that lead to the activation of second-messenger cascades and thus promoting angiogenic differentiation. Copyright 2001 Academic Press. [on SciFinder (R)] |
| Databáze: | OpenAIRE |
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