Cationic DMPC/DMTAP Lipid Bilayers: Molecular Dynamics Study

TL;DR

This study uses molecular dynamics simulations to explore how varying DMTAP concentration in DMPC/DMTAP lipid bilayers influences their structural and electrostatic properties, revealing non-monotonic area dependence and electrostatic effects.

Contribution

It provides detailed atomistic insights into how DMTAP composition affects lipid bilayer structure and electrostatics, highlighting non-monotonic behavior and ion interactions.

Findings

Area per lipid shows a non-monotonic dependence on DMTAP concentration.

Electrostatic interactions drive re-orientation of lipid headgroups.

Chloride ions predominantly bind to PC nitrogens, affecting screening.

Abstract

Cationic lipid membranes are known to form compact complexes with DNA and to be effective as gene delivery agents both in vitro and in vivo. Here we employ molecular dynamics simulations for a detailed atomistic study of lipid bilayers consisting of a mixture of cationic dimyristoyltrimethylammonium propane (DMTAP) and zwitterionic dimyristoylphosphatidylcholine (DMPC). Our main objective is to examine how the composition of the bilayers affects their structural and electrostatic properties in the liquid-crystalline phase. By varying the mole fraction of DMTAP, we have found that the area per lipid has a pronounced non-monotonic dependence on the DMTAP concentration, with a minimum around the point of equimolar mixture. We show that this behavior has an electrostatic origin and is driven by the interplay between positively charged TAP headgroups and the zwitterionic PC heads. This interplay leads to considerable re-orientation of PC headgroups for an increasing DMTAP concentration, and gives rise to major changes in the electrostatic properties of the lipid bilayer, including a significant increase of total dipole potential across the bilayer and prominent changes in the ordering of water in the vicinity of the membrane. Moreover, chloride counter-ions are bound mostly to PC nitrogens implying stronger screening of PC heads by Cl ions compared to TAP head groups. The implications of these findings are briefly discussed.