Bilayer edge and curvature effects on partitioning of lipids by tail length: atomistic simulations

The partitioning of lipids among different microenvironments in a bilayer is of considerable relevance to characterization of composition variations in biomembranes. Atomistic simulation has been ill-suited to model equilibrated lipid mixtures because the time required for diffusive exchange of lipids among microenvironments exceeds typical submicrosecond molecular dynamics trajectories. A method to facilitate local composition fluctuations, using Monte Carlo mutations to change lipid structures within the semigrand-canonical ensemble (at a fixed difference in component chemical potentials, Deltamu), was recently implemented to address this challenge. This technique was applied here to mixtures of dimyristoylphosphatidylcholine and a shorter-tail lipid, either symmetric (didecanoylphosphatidylcholine (DDPC)) or asymmetric (hexanoyl-myristoylphosphatidylcholine), arranged in two types of structure: bilayer ribbons and buckled bilayers. In ribbons, the shorter-tail component showed a clear enrichment at the highly curved rim, more so for hexanoyl-myristoylphosphatidylcholine than for DDPC. Results on buckled bilayers were variable. Overall, the DDPC content of buckled bilayers tended to exceed by several percent the DDPC content of flat ones simulated at the same Deltamu, but only for mixtures with low overall DDPC content. Within the buckled bilayer structure, no correlation could be resolved between the sign or magnitude of the local curvature of a leaflet and the mean local lipid composition. Results are discussed in terms of packing constraints, surface area/volume ratios, and curvature elasticity.