Cubic phases in phosphatidylethanolamine dispersions: Formation, stability and phase transitions

Abstract

The non-lamellar phases formed by membrane lipids in diluted aqueous dispersions are mainly represented by the inverted hexagonal phase, HII, and phases of cubic symmetry, among them the bicontinuous cubic phases Pn3m (Q²²⁴), Im3m (Q²²⁹) and Ia3d (Q²³⁰). Here we report X-ray diffraction data on phosphatidylethanolamine (PE) dispersions forming highly stable Im3m and Pn3m cubic phases at ambient temperature as a result of a temperature cycling through the Lα - HII transition and complement the structural characterization of the PE phase transitions with thermodynamic data obtained by differential scanning calorimetry and differential scanning densitometry. All studied PEs displayed irreversible two-state Im3m → Pn3m phase transitions in the range ∼75-85°C with enthalpy of ∼100cal/mol. By contrast with the Lα - HII transition, the Im3m → Pn3m transition was not accompanied by a stepwise change of the specific volume. The cubic phases induced in dipalmitoleoyl PE dispersions are of particular interest because of their facile formation, especially in the presence of small amounts of charged lipid admixtures, and long-term stability at physiologically relevant conditions in a broad temperature range around room temperature.

Keywords: Bicontinuous cubic phase; Cubic-cubic phase transition; DSC; Differential scanning densitometry; Phosphatidylethanolamines; X-ray diffraction.