Ion dynamics in cationic lipid bilayer systems in saline solutions

Positively charged lipid bilayer systems are a promising class of nonviral vectors for safe and efficient gene and drug delivery. Detailed understanding of these systems is therefore not only of fundamental but also of practical biomedical interest. Here, we study bilayers comprising a binary mixture of cationic dimyristoyltrimethylammoniumpropane (DMTAP) and zwitterionic (neutral) dimyristoylphosphatidylcholine (DMPC) lipids. Using atomistic molecular dynamics simulations, we address the effects of bilayer composition (cationic to zwitterionic lipid fraction) and of NaCl electrolyte concentration on the dynamical properties of these cationic lipid bilayer systems. We find that, despite the fact that DMPCs form complexes via Na+ ions that bind to the lipid carbonyl oxygens, NaCl concentration has a rather minute effect on lipid diffusion. We also find the dynamics of Cl- and Na+ ions at the water-membrane interface to differ qualitatively. Cl- ions have well-defined characteristic residence times of nanosecond scale. In contrast, the binding of Na+ ions to the carbonyl region appears to lack a characteristic time scale, as the residence time distributions displayed power-law features. As to lateral dynamics, the diffusion of Na+ ions within the water-membrane interface consists of two qualitatively different modes of motion: very slow diffusion when ions are bound to DMPC, punctuated by fast rapid jumps when detached from the lipids. Overall, the prolonged dynamics of the Na+ ions are concluded to be interesting for the physics of the whole membrane, especially considering its interaction dynamics with charged macromolecular surfaces