Phospholipid/cholesteryl ester microemulsions containing unesterified cholesterol: model systems for low density lipoproteins

As models for the effects of unesterified cholesterol (UC) on the lipid organization of low density lipoprotein (LDL), microemulsions containing either egg yolk phosphatidylcholine (EYPC) or dimyristoyl phosphatidylcholine (DMPC) as the surface component, cholesteryl oleate (CO) as the core component, and varying amounts of unesterified cholesterol were prepared by sonication. Gel filtration chromatography showed coelution of each of the lipid components, demonstrating the formation of well-defined microemulsion populations. Unesterified cholesterol incorporation into the microemulsions was proportional to the composition of the original mixture at low unesterified cholesterol compositions, but reached saturation at compositions of approximately 15 and 10 mol% unesterified cholesterol for EYPC/CO and DMPC/CO microemulsions, respectively. The Stokes' radius of the microemulsions was constant and similar to native LDL for initial compositions less than 15 mol% unesterified cholesterol, but increased at compositions above 15 mol%. In both EYPC/CO/UC and DMPC/CO/UC microemulsions, no significant changes were observed for the calorimetric or Van't Hoff enthalpy for the thermal transition of the core cholesteryl ester; however, increases in the transition temperature as a function of increasing unesterified cholesterol composition suggests that unesterified cholesterol has a stabilizing effect on the core transition. In DMPC/CO/UC microemulsions, the effect of unesterified cholesterol on the surface-located DMPC could be clearly observed as a broadening of the thermal transition of the acyl chains. These results demonstrate that unesterified cholesterol is located primarily in the surface of these protein-free lipid model systems for LDL.