Theory of Lipid Polymorphism: Application to Phosphatidylethanolamine and Phosphatidylserine

TL;DR

This paper develops a microscopic model of charged lipids to understand their phase behavior and polymorphism, successfully replicating experimental phase transitions and explaining lipid behavior under different conditions.

Contribution

It introduces a detailed microscopic model incorporating Coulomb and short-range interactions, providing insights into lipid phase behavior and polymorphism.

Findings

Model reproduces known lyotropic phases.

Phase transition from inverted hexagonal to lamellar with increased charge.

Explains lipid polymorphism under varying pH and hydration.

Abstract

We introduce a microscopic model of a lipid with a charged headgroup and flexible hydrophobic tails, a neutral solvent, and counter ions. Short-ranged interactions between hydrophilic and hydrophobic moieties are included as are the Coulomb interactions between charges. Further, we include a short-ranged interaction between charges and neutral solvent, which mimics the short-ranged, thermally averaged interaction between charges and water dipoles. We show that the model of the uncharged lipid displays the usual lyotropic phases as a function of the relative volume fraction of the headgroup. Choosing model parameters appropriate to dioleoylphosphatidylethanolamine in water, we obtain phase behavior which agrees well with experiment. Finally we choose a solvent concentration and temperature at which the uncharged lipid exhibits an inverted hexagonal phase and turn on the headgroup charge. The lipid system makes a transition from the inverted hexagonal to the lamellar phase which is related to the increased waters of hydration correlated with the increased headgroup charge via the charge-solvent interaction. The polymorphism displayed upon variation of pH mimics that of the behavior of phosphatidylserine.