Computational and Experimental Study of Dope and Pope Lipids in the Inverted Hexagonal Phase: Effect of Water per Lipid, Temperature, Salt Concentration, and Simulation Setup

Abstract

Non-lamellar lipid phases such as the inverted hexagonal (HII) phase are of special interest in nanomedicine, e.g. in the drug/gene release step of intracellular therapeutic delivery to the target cell. In this study, the structural properties, including the deuterium order parameters and lattice distance, of DOPE lipids in the HII phase were studied as a function of temperature using molecular dynamics (MD) simulation, NMR, and SAXS experiments. MD simulation was also used to provide deeper insights into the effect of water per lipid (WPL) and salt concentration on both structural and dynamical properties of DOPE and POPE systems in HII phase. The preliminary results suggest that the WPL has a high impact on both deuterium order parameter and lattice distance. In principle, to be consistent and comparable with experimental data, the WPL in the simulation should be the same to the one in the corresponding experimental setup. However, the accurate measurement of the WPL inside the water channels of the HII phase is challenging experimentally since it requires the experiments to be conducted in the low WPL regime. Given well-established force field parameters for the lipids, which is the case for both DOPE and POPE lipids, computer simulation can assist experimentalists in estimating the WPL. In addition, this will provide a methodology for lipid force field parameter development in situations where only experimental data in the HII phase are available for that specific lipid. Finally, since experimental data for DOPE and POPE lipids in the HII phase is available, these systems can form frameworks to validate the simulation setup for HII systems required for the study of other lipids or lipid mixtures in this phase.