Cationic DMPC/DMTAP Lipid Bilayers: Molecular Dynamics Study

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.

References in corpus (2)

• Molecular Dynamics Simulations of Lipid Bilayers: Major Artifacts due to Truncating Electrostatic Interactions
• Systematic comparison of force fields for microscopic simulations of NaCl in aqueous solutions: Diffusion, free energy of hydration and structural properties

Cited by in corpus (5)

• Subdiffusion and lateral diffusion coefficient of lipid atoms and molecules in phospholipid bilayers
• Motional Coherence in Fluid Phospholipid Membranes
• Investigating Interactions of Biomembranes and Alcohols: A Multiscale Approach
• Effective potentials and electrostatic interactions in self-assembled molecular bilayers II: the case of biological membranes
• Lateral-Pressure Profiles in Cholesterol-DPPC Bilayers