Thermodynamics and Mechanism of the Association of Plasma Apolipoproteins with Synthetic Phosphatidylcholines

Abstract

Two fundamental question in our investigations of lipoprotein structure and function have been how do lipoproteins form, and what factors contribute to lipoprotein stability. In the simplest sense, apolipoproteins might be considered as polymeric detergents: within lipoproteins, the apolipoproteins, phospholipids, and cholesterol form a surface monolayer, which separates a core of neutral lipids from an external aqueous compartment. In the crudest verification of lipid-protein association, one finds that most of the plasma apolipoproteins spontaneously associate with highly turbid multibi-layers of phospholipid to form small lipid-protein complexes that are optically clear. In all such reassembly studies it has been found that phospholipids alone or with neutral lipids form complexes, but that the neutral lipids do not associate with apolipoproteins in the absence of phospholipids. Therefore, the phospholipid-apolipoprotein interaction would appear to be a key structural unit in the organization of a lipoprotein. It is the structure and dynamics of this association which we will attempt to correlate with what is known about the structure of lipoproteins, lipids and apoproteins.