Ion Dynamics in Cationic Lipid Bilayer Systems in Saline Solutions

Abstract

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.

Simulations of Micellization of Sodium Hexyl Sulfate

“…It has also been shown that the content of a charged lipid/surfactant together with salt content is important in determining both static and dynamic properties of bilayers. 77 In micelles, the length of the hydrocarbon tail has a strong contribution to both dynamics and static properties as the difference between this study and refs 32 and 33 show.…”

Molecular electrometer and binding of cations to phospholipid bilayers

“…In such a comparison between experiments 32,49 and previously published Berger-modelbased simulations 50 , we could not rule out overestimation of order parameter response to bound cations (slopes m α and m β ), see ESI † . This might, in principle, explain the overestimated order parameter response of the Berger model to CaCl 2 , but not to NaCl (see discussion in ESI † ).…”

Molecular Dynamics Study of Oxidized Lipid Bilayers in NaCl Solution

“…47−52 Independent of the force-field, characteristic times for ion binding to the bilayer were found to be long, at least 30 ns for sodium ions and 100 ns for divalent calcium ions. 43,47 The residence time distributions of cations (Na + ) and anions (Cl − ) were found to be different: 47 For Cl − , an exponential decay was reported but the Na + resident time appeared to follow a power law explaining the observed long resident times. 47 The binding of cations has a significant impact on the structural and dynamical properties of PC membranes.…”