  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.
