Phase behavior of mixed phosphatidylglycerol/phosphatidylcholine multilamellar and unilamellar vesicles

The phase behavior of dipentadecanoylphosphatidylglycerol (DC15PG)/dimyristoylphosphatidylcholine (DMPC) mixtures has been studied in both small, unilamellar vesicles and large, multilamellar vesicles. We have used both the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and high-sensitivity differential scanning calorimetry to detect temperature-dependent changes in membrane structure. Electron microscopy has demonstrated different fracture face morphologies for large, multilamellar vesicles depending on sample composition and temperature. These data have been interpreted in terms of proposed phase diagrams for this lipid mixture. The shapes of the proposed phase diagrams have led us to conclude that DMPC and DC15PG mix freely in the plane of a lipid bilayer only at less than 50 mol % DC15PG. At higher DC15PG content, the data have been interpreted as reflecting substantial compositional inhomogeneities in the plane of the bilayer, if not phase immiscibility, even in the fluid phase. In addition, small vesicles containing greater than 50 mol % DC15PG were unstable in the ordered phase and spontaneously converted to larger vesicles. Finally, the anisotropy of DPH fluorescence was found to be invariant with DC15PG content at temperatures just above the liquidus phase line in small, unilamellar vesicles. This demonstrated that inclusion of negatively charged phosphatidylglycerol does not noticeably affect the order within the acyl chain region of the bilayer, relative to phosphatidylcholine.