Interaction of room temperature ionic liquid solutions with a cholesterol bilayer.

Water solutions of representative ([C4mim][Cl] and [C4mim][Tf2N]) room temperature ionic liquids (ILs) in contact with a neutral lipid bilayer made of cholesterol molecules has been investigated by molecular dynamics simulations based on an empirical force field model. The results show that both ILs display selective adsorption at the water-cholesterol interface, with partial inclusion of ions into the bilayer. In the case of [C4mim][Cl], the adsorption of ions at the water-cholesterol interface is limited by a sizable bulk solubility of the IL, driven by the high water affinity of [Cl]-. The relatively low solubility of [C4mim][Tf2N], instead, gives rise to a nearly complete segregation of the IL component on the bilayer, altering its volume, compressibility, and electrostatic environment. The computational results display important similarities to the results of recent experimental measurements for ILs in contact with phospholipid model membranes (see Evans, K. O. Int. J. Mol. Sci. 2008, 9, 498-511 and references therein).

Structural motifs of cholesterol nanoparticles.

The growth sequence of gas-phase cholesterol clusters (Ch(N)) with up to N=36 molecules has been investigated by atomistic simulation based on an empirical force field model. The results of long annealings from high temperature show that the geometric motifs characterizing the structure of pure cholesterol crystals already appear in nanometric aggregates. In all clusters molecules tend to align along a common direction. For cluster sizes above the smallest ones, dispersion interactions among the hydrocarbon body and tails of cholesterol cooperate with hydrogen bonding to give rise to a bilayer structure. Analysis of snapshots from the annealing shows that the condensation of hydrogen bonds into a connected network of rings and chains is an important step in the self-organization of cholesterol clusters. The effect of solvation on the equilibrium properties of medium-size aggregates is investigated by short molecular dynamics simulations for the N=30 and N=40 clusters in water at near ambient conditions and in supercritical carbon dioxide at T=400 K.

Amphiphilic character and aggregation properties of small cholesterol islands on water: a simulation study.

Small cholesterol clusters (Ch(n), 1 < or = n < or = 10) on water have been investigated by molecular dynamics simulations based on an empirical force field potential. The simulation results for clusters of increasing size highlight the processes that take place during the initial stages of cholesterol aggregation at low coverage. Our results show that at T = 280 K clusters form spontaneously out of a dilute two-dimensional (2D) vapor of cholesterol molecules, driven by entropy and potential energy. Up to n = 10, corresponding to 25% coverage for our simulation cell, cholesterol molecules lay flat on the water surface, forming fluid-like 2D aggregates. Within each island, the elongated cholesterol molecules align their longest axis along a common direction, anticipating the liquid-crystal character of bulk phases. With increasing cluster size, the adsorption energy per molecule quickly saturates to a value close to the limiting value for a full monolayer coverage. Cholesterol adsorption locally changes the electrostatic surface polarization of water, giving rise to an induced moment that tends to compensate the dipole of the adsorbed island. Computations for a single cholesterol molecule and dimer in bulk water are reported for a comparison. The absorption energy of both species in bulk water is larger than their adsorption energy at the water surface, thus pointing to entropy as the origin of the amphiphilic character of cholesterol.