SQUALENE PROMOTES THE FORMATION OF NONBILAYER STRUCTURES IN PHOSPHOLIPID MODEL MEMBRANES

A study of the lipid polymorphism of aqueous dispersions of stearoylol eoylphosphatidylethanolamine and palmitoyloleoylphosphatidylcholine (9 5:5, mol/mol) in the presence of the hydrophobic molecule squalene, an intermediate in the biosynthesis of sterols, has been performed. With increasing concentration of squalene the main transition temperature was decreased from 29.8-degrees-C for the pure phospholipid system to 28.1-degrees-C for samples containing 5 mol% squalene without consider able changes in the phase transition enthalpy as detected by high prec ision differential scanning calorimetry. The structure of the phosphol ipid aggregates was determined by small- and wide-angle X-ray diffract ion experiments showing only a minor increase of the lamellar repeat d istance of the liquid-crystalline phase for the squalene containing sa mples. By far more pronounced was the effect of squalene on the lamell ar-to-inverse-hexagonal phase transition, which was shifted from 64-de grees-C to about 36-degrees-C in the presence of 6 mol% squalene, ther eby overlapping with the main transition. X-ray data showed that the s ize of the tubes of the inverse hexagonal phase are increasing linearl y up to 6 mol% squalene. Experiments performed in the presence of 10 m ol% squalene did not further change the phase behaviour, indicating th e limiting partition of this hydrophobic molecule into the membrane. T he high efficiency of squalene to promote the formation of the inverse hexagonal phase is discussed along the lines of argument based on the model of Kirk et al. (Kirk, G.L., Gruner, S.M. and Stein, D.E. (1984) Biochemistry 23, 1093-1102).