Effect of PEG-lipid conjugates on the phase behavior of phosphatidylethanolamine dispersions

Abstract

The phase behavior of binary mixtures of hydrated dielaidoylphosphatidylethanolamine (DEPE) with two different PEG-lipid conjugates at a molar fraction below 0.2 has been studied by using time-resolved X-ray diffraction, and partial phase diagrams have been constructed. The studied conjugates comprise two saturated hydrocarbon acyl chains 14 carbon atoms long and PEG550 or PEG5000 chains covalently attached to a phosphoethanolamine polar head group, DMPE(PEG550) and DMPE(PEG5000), respectively. When added in small amounts (10–20 mol%) to DEPE aqueous dispersions, both PEG-lipids favor the lamellar liquid crystalline (L α ) phase at the expense of the lamellar gel (L β ) and the inverted hexagonal (H II) phases. One of the conjugates, DMPE(PEG550), shifts the L α –H II transition of DEPE to higher temperatures by 2.5°C per mol% PEG-lipid, and induces the spontaneous formation of a cubic phase of space group Im3m in the DEPE dispersions. The cubic phase intrudes between the lamellar liquid crystalline and the inverted hexagonal phases in the DEPE/DMPE(PEG550) phase diagram. Low amounts of the DMPE(PEG5000) conjugate only shift the L α –H II transition of DEPE to higher temperatures, at 5.2°C per mol% PEG-lipid, but does not promote the formation of additional phases. The respective slopes for the L β –L α transition temperature depression are 10–15 times smaller. At >15 mol% DMPE(PEG550) and at >5 mol% DMPE(PEG5000), the non-lamellar phases are eliminated from the phase diagrams. Structural data on the organization of the pure hydrated PEG-lipid conjugates are also provided, suggesting that these lipids form micelles and lamellae.