We study the influence of truncating the electrostatic interactions in a fully hydrated pure dipalmitoylphosphatidylcholine (DPPC) bilayer through 20 ns molecular dynamics simulations. The computations in which the electrostatic interactions were truncated are compared to similar simulations using the particle-mesh Ewald (PME) technique. All examined truncation distances (1.8-2.5 nm) lead to major effects on the bilayer properties, such as enhanced order of acyl chains together with decreased areas per lipid. The results obtained using PME, on the other hand, are consistent with experiments. These artifacts are interpreted in terms of radial distribution functions g(r) of molecules and molecular groups in the bilayer plane. Pronounced maxima or minima in g(r) appear exactly at the cutoff distance indicating that the truncation gives rise to artificial ordering between the polar phosphatidyl and choline groups of the DPPC molecules. In systems described using PME, such artificial ordering is not present.

We employ 100-ns molecular dynamics simulations to study the influence of cholesterol on structural and dynamic properties of dipalmitoylphosphatidylcholine bilayers in the fluid phase. The effects of the cholesterol content on the bilayer structure are considered by varying the cholesterol concentration between 0 and 50%. We concentrate on the free area in the membrane and investigate quantities that are likely to be affected by changes in the free area and free volume properties. It is found that cholesterol has a strong impact on the free area properties of the bilayer. The changes in the amount of free area are shown to be intimately related to alterations in molecular packing, ordering of phospholipid tails, and behavior of compressibility moduli. Also the behavior of the lateral diffusion of both dipalmitoylphosphatidylcholine and cholesterol molecules with an increasing amount of cholesterol can in part be understood in terms of free area. Summarizing, our results highlight the central role of free area in comprehending the structural and dynamic properties of membranes containing cholesterol.

To gain a better understanding of how monovalent salt under physiological conditions affects plasma membranes, we have performed 200 ns atomic-scale molecular dynamics simulations of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipid bilayers. These two systems provide representative models for the outer and inner leaflets of the plasma membrane, respectively. The implications of cation-lipid interactions in these lipid systems have been considered in two different aqueous salt solutions, namely NaCl and KCl, and the sensitivity of the results on the details of interactions used for ions is determined by repeating the simulations with two distinctly different force fields. We demonstrate that the main effect of monovalent salt on a phospholipid membrane is determined by cations binding to the carbonyl region of a membrane, while chloride anions mostly stay in the water phase. It turns out that the strength and character of the cation-lipid interactions are quite different for different types of lipids and cations. PC membranes and Na + ions demonstrate strongest interactions, leading to notable membrane compression. This finding was confirmed by both force fields (Gromacs and Charmm) employed for the ions. The binding of potassium ions to PC membranes (and the overall effect of KCl), in turn, was found to be much weaker mainly due to the larger size of a K + ion compared to Na + . Furthermore, the effect of KCl on PC membranes was found to be force-field sensitive: The binding of a potassium ion was not observed at all in simulations performed with the Gromacs forcefield, which seems to exaggerate the size of a K + ion. As far as PE lipid bilayers are concerned, they are found to be influenced by monovalent salt to a significantly lesser extent compared to PC bilayers, which is a direct consequence of the ability of PE lipids to form both intra-and intermolecular hydrogen bonds and hence to adopt a more densely packed bilayer structure. Whereas for NaCl we observed weak binding of Na + cations to the PE lipid-water interface, in the case of KCl we witnessed almost complete lack of cation binding. Overall, our findings indicate that monovalent salt ions affect lipids in the inner and outer leaflets of plasma cell membranes in substantially different ways.

Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins. In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches.