Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion. its anionic polysugar side chains are stretched out into the blood substitute solution representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that low density lipoprotein (LDL) strongly deposited at the proteoheparan sulfate, particularly in the presence of Ca2+. On the other hand. high density lipoprotein (HDL) bound to heparan sulfate proteoglycan (HS-PG) protected against LDL docking even at high LDL and Ca2+ concentrations and completely suppressed calcification of the protcoglycan-lipo-protein complex. These findings correlate well with those obtained from clinical investications on risk factors for arteriosclerosis. The most important patient-oriented finding was the at least four times higher affinity constant of HDL binding to the proteoglvcan receptor as compared to LDL docking. Therefore, under normal in vivo conditions most of the proteoglycan receptors are occupied by HDL and in this way shielded against LDL binding. Since competition is the dominant rule at the receptor site. the ternary complex HS-PG,LDL Ca2+-aggregation can be reversed by HDL. Altogether, the proteoglycan coated hydrophobic silica surface used in these experiments. mimics the endothelial cell membrane in quite a perfect manner with respect to lipoprotein interactions. at the blood -endothelium-matrix interface. (C) 2002 Published by Elsevier Science B.V.