X-ray diffraction study of the polymorphic behavior of N-methylated dioleoylphosphatidylethanolamine

Area of Science:

• Lipid polymorphism
• Materials science
• Biophysics

Background:

• Aqueous dispersions of phospholipids exhibit complex phase behaviors.
• Dioleyolphosphatidylethanolamine (DOPE) and its N-methylated analogues (DOPE-Me, DOPE-Me2, DOPC) are model systems for studying lipid polymorphism.

Purpose of the Study:

• To investigate the polymorphic phase behavior of DOPE and its N-methylated analogues.
• To correlate phase transitions with the spontaneous radius of curvature (R0) of lipid monolayers.

Main Methods:

• X-ray diffraction was used to analyze the phase behavior of hydrated lipid dispersions.
• Temperature-dependent studies were performed to observe phase transitions.
• Lattice spacings were analyzed to infer the spontaneous radius of curvature (R0).

Main Results:

• Increasing N-methylation of DOPE significantly alters interlamellar water width and phase transition temperatures.
• DOPE and DOPE-Me exhibit transitions to inverted hexagonal (HII) phases, while DOPE-Me2 and DOPC remain in lamellar (L alpha) phases up to 85°C.
• DOPE-Me shows complex, slow, non-equilibrium transitions, including disordering and formation of cubic phases, influenced by lipid degradation.
• The spontaneous radius of curvature (R0) increases with N-methylation, correlating with observed phase behaviors.

Conclusions:

• The spontaneous radius of curvature (R0) is a key parameter predicting lipid mesomorphic behavior.
• Small R0 (DOPE) favors facile L alpha-HII transitions.
• Intermediate R0 (DOPE-Me) leads to complex non-equilibrium behavior and cubic phase formation.
• Large R0 (DOPC) favors stable L alpha phases.
• Minimal periodic surfaces may represent equilibrium cubic phases by maintaining constant R0 and monolayer thickness.