Effect of phosphatidylethanolamine on the properties of phospholipid-apolipoprotein complexes

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Abstract
Plasma high density lipoproteins (HDL) are synthesized in intestinal mucosal cells and hepatocytes and are secreted into the blood. Factors influencing the structure and function of these HDL, such as lipid and protein composition, are poorly understood. It appears, however, that intracellular, discoidal HDL are enriched, relative to plasma HDL, in phosphatidylethanolamine (PE), a phospholipid known to generate unusual, nonbilayer structures of putative physiological significance. Although incubation of dimyristoylphosphatidylcholine (DMPD) with apolipoprotein A-I at the gel-liquid crystalline phase transition temperature results in the spontaneous formation of lipid-protein complexes, the presence of proportionately small amounts of PE prevents the formation of such complexes, suggesting that PE profoundly alters the phase properties of the phospholipid bilayers. However, by using a detergent-mediated method for the formation of PE-rich model nascent HDL from phospholipids and apolipoprotein A-I, lipid-protein complexes containing as much as 75% DLPE could be formed, thus demonstrating that the presence of PE causes a kinetic, rather than a thermodynamic, barrier to spontaneous complex formation. The products contained a DLPE:DMPC molar ratio similar to that of the initial incubation mixture; however, as the mole percentage of DLPE increased, the products became less heterogeneous, the buoyant density of the products increased, and the Stokes diameter of the products decreased. Similar results were obtained when dimyristoylphosphatidylethanolamine (DMPE) and dipalmitoylphosphatidylethanolamine (DPPE) were employed in lieu of DLPE. Electron microscopy of complexes containing DLPE and DMPC at a 1:1 molar ratio showed that these particles possessed a discoidal, bilayer morphology similar to that seen with complexes containing only phosphatidylcholine. PE increased the susceptibility of the particles to denaturation by guanidine hydrochloride and caused a much sharper endotherm at the phase transition as shown by differential scanning calorimetry; however, circular dichroism studies showed that the A-I secondary structure was similar in complexes with DMPC alone and when complexed with a mixture of DMPC and DLPE. The results from these experiments suggest that the presence of DLPE in a mixture with DMPC diminishes the interaction between protein and lipid in these complexes. We conclude that under appropriate conditions, phosphatidylethanolamines can be incorporated into model nascent HDL, but the presence of PE significantly alters certain of the physical properties of these HDL, such as size and density, compared to those prepared with phosphatidylcholines alone.