Molecular Modeling of the Lamellar to Inverse Hexagonal Phase Transition in Dope-Dopc Lipid Systems

Abstract

In the proper physiological state, myelin sheaths consist of tightly packed lipids and proteins and insulate neurons in both the central and peripheral nervous systems. However, defective myelin sheaths in multiple sclerosis (MS), and other demyelinating diseases, ultimately cause vesiculation of the lipids contained in the sheaths. Increasing the proportion of phosphatidylethanolamine in myelin was shown experimentally to cause structural instabilities due to an abnormal packing structure. The unstable form favors inverted hexagonal phases as a result of lipid headgroup size and geometry, whereas normal myelin composition favors a smooth lamellar phase. Through a molecular mean field theory approach, we produce phase diagrams of lipid systems with varying concentrations of phosphatidylethanolamine and phosphatidylcholine to capture the transitions between inverted hexagonal and lamellar phases. Analyzing structural instabilities in myelin sheaths may provide us with a clearer understanding of multiple sclerosis and other demyelinating diseases.