Fusion of low density lipoproteins with cholesterol ester-phospholipid microemulsions. Prevention of particle fusion by apolipoprotein A-I.

Little is known about the mechanism and control of lipoprotein particle fusion, although apoproteins are presumed to be important in maintenance of particle structure. This study characterizes the interaction of apo-B-containing low density lipoproteins (LDL) with cholesterol ester microemulsions (CEME) in the presence and absence of apo-A-I to determine if a role for these apoproteins in particle integrity could be ascertained. CEME are an apoprotein-free analog of LDL formed by sonication of radiolabeled phospholipid (surface) and cholesterol ester (core). Incubation of CEME with LDL followed by precipitation of LDL with MnCl2 resulted in coprecipitation of CEME with LDL that was time-, temperature-, and concentration-, but not pH (pH 6-9)-, dependent and occurred over a wide range of CEME and LDL particle compositions. Particles from the incubation were larger than the unincubated particles and intermediate in density and electrophoretic mobility between the starting LDL and CEME. Differential scanning calorimetry experiments suggested that CEME surface and core lipids had mixed with those of LDL. When particles from incubations were exposed to an anti-apo-B column, radiolabeled surface and core molecules originating from the CEME particles bound to the column. Particles eluted at low pH from the anti-apo-B column were irregularly shaped and had excess surface material as judged by electron microscopy. Incubation of CEME with LDL in the presence of 3 M KBr or 4% bovine serum albumin did not alter the interaction of the particles. However, incubation of CEME with LDL in the presence of apo-A-I (2:1 CEME cholesterol-to-apo-A-I mass ratio) greatly reduced the interaction of the LDL and CEME particles. We conclude that the incubation of CEME with isolated LDL resulted in particle fusion that was prevented by apo-A-I.