Molecular packing of high-density and low-density lipoprotein surface lipids and apolipoprotein A-I binding

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Abstract
The surface pressure (.pi.)-molecular area (A) isotherms for monolayers of human high-density lipoprotein (HDL3) and low-density lipoprotein (LDL) phospholipids and of mixed monolayers of these phospholipids with cholesterol spread at the air-water interface were used to deduce the likely molecular packing at the surfaces of HDL3 and LDL particles. LDL phospholipids form more condensed monolayers than HDL3 phospholipids; for example, the molecular areas of LDL and HDL3 phospholipids at .pi. = 10 dyn/cm are 88 and 75 .ANG.2/molecule, respectivley. The closer packing in the LDL phospholipid monolayer can be attributed to the higher contents of saturated phosphatidylcholines an sphingomyelin relative to HDL3. Cholesterol condenses both HDL3 and LDL phospholipid monolayers but has a greater condensing effect on the LDL phospholipid monolayer. The .pi.-A isotherms for mixed monolayers of HDL3 phospholipid cholesterol and LDL phospholipid/cholesterol at stoichiometries similar to those at the surfaces of lipoprotein particles suggest that the monolayer at the surface of the LDL particle is significantly more condensed than that at the surface of the HDL3 particle. The closer lateral packing in LDL is due to at least three factors: (1) the difference in phospholipid composition; (2) the higher unesterified cholesterol content in LDL; and (3) a stronger interaction between cholesterol and LDL phospholipids relative to HLD3 phospholipids. The influence of lipid molecular packing on the affintiy of human apolipoprotein A-I (apo A-I) for HDL3 and LDL surface lipids was evaluated by monitoring the adsorption of 14C-methylated apo A-I to monolayers of these lipids spread at various initial surface pressures (.pi.i). At a given (.pi.i), apo A-I adsorbs more to the HDL3 surface lipid monolayer than to the LDL surface lipid monolayer and fails to adsorb to the HDL3 and LDL surface lipid monolayers at .pi.i .gtoreq. 26 and 20 dyn/cm, respectively. Cholesterol generally decreases the adsorption of apo A-I to the lipoprotein surface lipid monolayers. These studies suggest that the molecular packing at the surface of lipoprotein particles influences the binding of apo A-I and that the surface lipid composition of LDL is, at least partially, the reason for the absence of apo A-I in LDL particles in vivo.