Effect of cholesterol and ergosterol on the compressibility and volume fluctuations of phospholipid-sterol bilayers in the critical point region: a molecular acoustic and calorimetric study.

Although sterol-phospholipid interactions have been of interest for many years now, a complete thermodynamic profile of these systems is still missing. To contribute to a better understanding of the thermodynamic functions of these systems, we determined isothermal compressibility coefficient data for dipalmitoylphosphocholine (DPPC) and DPPC-containing cholesterol and ergosterol vesicles by means of molecular acoustics (ultrasound velocimetry and densimetry) and differential scanning and pressure perturbation calorimetric techniques. A particular focus was on the influence of the differential structural properties of the two sterols on the thermodynamic properties of lipid bilayers, and on the nature of the critical point region of phospholipid-sterol systems by determining thermodynamic fluctuation parameters. Contrary to significant changes in conformational and dynamical properties of the DPPC-sterol membranes, no marked differences were found in the various thermodynamic properties studied, including the adiabatic (beta(S)(lipid)) and isothermal (beta(T)(lipid)) compressibility, as well as the volume fluctuations. Differences in beta(T)(lipid) and beta(S)(lipid) become dramatic in the gel-fluid transition region only, due to a significant degree of slow relaxational processes in the microsecond time range in the transition region. Our data show no evidence for the existence of a typical critical point phenomenon in the concentration and temperature range where a critical point in the DPPC-sterol phase diagram is expected to appear. Hence, on a macroscopic level, it seems more appropriate to describe the sterol-phospholipid binary mixtures in the liquid-ordered/liquid-disordered coexistence region as a phase region consisting essentially of small nanodomains only. Such small-domain dimensions, with a series of particular properties such as increased line energy, spontaneous curvature, and limited lifetime, seem also to be typical of raftlike domains in cell membranes.