Lateral-Pressure Profiles in Cholesterol-DPPC Bilayers

By means of atomistic molecular dynamics simulations, we study cholesterol-DPPC (dipalmitoyl phosphatidylcholine) bilayers of different composition, from pure DPPC bilayers to a 1:1 mixture of DPPC and cholesterol. The lateral-pressure profiles through the bilayers are computed and separated into contributions from the different components. We find that the pressure inside the bilayer changes qualitatively for cholesterol concentrations of about 20% or higher. The pressure profile then turns from a rather flat shape into an alternating sequence of regions with large positive and negative lateral pressure. The changes in the lateral-pressure profile are so characteristic that specific interaction between cholesterol and molecules such as membrane proteins mediated solely via the lateral-pressure profile might become possible

Systematic comparison of force fields for microscopic simulations of NaCl in aqueous solutions: Diffusion, free energy of hydration and structural properties

In this paper we compare different force fields that are widely used (Gromacs, Charmm-22/x-Plor, Charmm-27, Amber-1999, OPLS-AA) in biophysical simulations containing aqueous NaCl. We show that the uncertainties of the microscopic parameters of, in particular, sodium and, to a lesser extent, chloride translate into large differences in the computed radial-distribution functions. This uncertainty reflects the incomplete experimental knowledge of the structural properties of ionic aqueous solutions at finite molarity.We discuss possible implications on the computation of potential of mean force and effective potentials.Comment: Revised and extended manuscrip

Stability of charge inversion, Thomson problem and application to electrophoresis

We analyse charge inversion in colloidal systems at zero temperature using stability concepts, and connect this to the classical Thomson problem of arranging electrons on sphere. We show that for a finite microion charge, the globally stable, lowest energy state of the complex formed by the colloid and the oppositely charged microions is always overcharged. This effect disappears in the continuous limit. Additionally, a layer of at least twice as many microions as required for charge neutrality is always locally stable. In an applied external electric field the stability of the microion cloud is reduced. Finally, this approach is applied to a system of two colloids at low but finite temperature

Cationic DMPC/DMTAP Lipid Bilayers: Molecular Dynamics Study

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

Coarse-Grained Model for Phospholipid/Cholesterol Bilayer

We construct a coarse-grained (CG) model for dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayers and apply it to large-scale simulation studies of lipid membranes. Our CG model is a two-dimensional representation of the membrane, where the individual lipid and sterol molecules are described by point-like particles. The effective intermolecular interactions used in the model are systematically derived from detailed atomic-scale molecular dynamics simulations using the Inverse Monte Carlo technique, which guarantees that the radial distribution properties of the CG model are consistent with those given by the corresponding atomistic system. We find that the coarse-grained model for the DPPC/cholesterol bilayer is substantially more efficient than atomistic models, providing a speed-up of approximately eight orders of magnitude. The results are in favor of formation of cholesterol-rich and cholesterol-poor domains at intermediate cholesterol concentrations, in agreement with the experimental phase diagram of the system. We also explore the limits of the novel coarse-grained model, and discuss the general validity and applicability of the present approach

Structural Effects of Small Molecules on Phospholipid Bilayers Investigated by Molecular Simulations

We summarize and compare recent Molecular Dynamics simulations on the interactions of dipalmitoylphosphatidylcholine (DPPC) bilayers in the liquid crystalline phase with a number of small molecules including trehalose, a disaccharide of glucose, alcohols, and dimethylsulfoxide (DMSO). The sugar molecules tend to stabilize the structure of the bilayer as they bridge adjacent lipid headgroups. They do not strongly change the structure of the bilayer. Alcohols and DMSO destabilize the bilayer as they increase its area per molecule in the bilayer plane and decrease the order parameter. Alcohols have a stronger detrimental effect than DMSO. The observables which we compare are the area per molecule in the plane of the bilayer, the membrane thickness, and the NMR order parameter of DPPC hydrocarbon tails. The area per molecule and the order parameter are very well correlated whereas the bilayer thickness is not necessarily correlated with them.Comment: 8 pages, 3 figures, accepted to Fluid Phase Equilibri