Atomistic Simulations of Mixed-Lipid Bilayers in Gel and Fluid Phases

The slow rate of diffusive mixing poses a challenge for molecular dynamics (MD) simulation studies of mixed-lipid bilayers. A mixed Monte Carlo-molecular dynamics (MC-MD) approach, which uses mutation moves to swap lipid types throughout the system within the semi-grand canonical ensemble, is here applied to a comparison of binary mixtures in the gel and liquid crystalline phases. The two lipid components modeled, distearoylphosphatidylcholine (DSPC) and dimyristoylphosphatidylcholine (DMPC), differ by four carbons in the lengths of their acyl tails and are investigated here at full hydration at a temperature (313 K) between their transition temperatures, where coexistence between a DSPC-rich gel phase and a DMPC-rich liquid crystalline phase is expected. An analysis of DSPC-DMPC mixtures in the gel phase indicates strong deviation from ideality in the thermodynamics of mixing, accompanied by a tendency of the shorter-tailed component DMPC to associate laterally and for DMPC headgroups to be displaced toward the bilayer midplane. The liquid crystal phase mixtures, in contrast, show more mild deviation from thermodynamically ideal mixing with no apparent tendency for similar lipids to cluster laterally and no difference in headgroup normal distribution profiles.