| Lipid multilayer systems have been studied experimentally for years using surface force apparatus, atomic force microscopy and osmotic pressure studies. The hydration level of the system is varied, changing the separation between the bilayers, in order to understand the forces that the bilayers feel as they are brought together. These studies have found a strongly repulsive force when the bilayers are close to each other, which has been termed the "hydration force", though the origins of this force are not clearly understood. We use computational molecular dynamics simulations of lipid bilayer systems to reproduce this phenomenon and gain insight into its molecular origins. We employ a multiscale approach in order to gain both detailed information from the atomistic work as well as better converged big picture results from the coarse-grained approaches. Using approximately 240 all-atom, 200 coarse-grained and 110 restricted primitive double bilayer systems, we examine the thermodynamic and structural changes that occur as a phosphatidylcholine lipid bilayer stack is dehydrated. To understand the forces between bilayers, we calculate the relative free energy change as the bilayers approach each other and are able to closely reproduce the repulsive behavior seen in experimental systems. We then break this free energy into entropic and enthalpic components in order to gain greater knowledge of the thermodynamic trends underlying the behavior. The atomistic simulations also capture microscopic adjustments which are seen experimentally as bilayers approach each other: decreases in diffusion constants, slowing of reorientational motion, and redistribution of hydrogen bonds. The restricted primitive model represents water simply by a dielectric constant but is able to recreate a similar electrical potential profile across the bilayer and capture similar thermodynamic trends. The coarse-grained model did not correctly reproduce the potential profile and was determined to be unsuitable for this study. The models are consistent in pointing toward solvent ordering effects as being essential in causing the repulsion as the bilayers come together. Further work on larger bilayer patches to include bilayer undulation and longer timescales to allow greater lipid reorganization may show greater involvement from the lipids as well. |
