Atomistic simulations of a multicomponent asymmetric lipid bilayer

TL;DR

This study uses atomistic molecular dynamics simulations to explore the physical properties and domain formation in an asymmetric multicomponent lipid bilayer, revealing insights into lipid partitioning, tilt behavior, and diffusion relevant to membrane function.

Contribution

It provides detailed atomistic insights into the formation and properties of asymmetric lipid domains, including lipid partitioning and tilt correlations, which were not previously characterized in such detail.

Findings

Cholesterol and SM form enriched domains in the bilayer.

Cholesterol partitions into SM-rich regions at a 3:1 ratio compared to POPC.

SM molecules exhibit tilt and long-range tilt correlations within domains.

Abstract

The cell membrane is inherently asymmetric and heterogeneous in its composition, a feature that is crucial for its function. Using atomistic molecular dynamics simulations, the physical properties of a 3-component asymmetric mixed lipid bilayer system comprising of an unsaturated POPC (palmitoyl-oleoyl-phosphatidyl-choline), a saturated SM (sphingomyelin) and cholesterol are investigated. In these simulations, the initial stages of liquid ordered, $l_o$, domain formation are observed and such domains are found to be highly enriched in cholesterol and SM. The current simulations also suggest that the cholesterol molecules may partition into these SM-dominated regions in the ratio of $3:1$ when compared to POPC-dominated regions. SM molecules exhibit a measurable tilt and long range tilt correlations are observed within the $l_o$ domain as a consequence of the asymmetry of the bilayer, with implications to local membrane deformation and budding. Tagged particle diffusion for SM and cholesterol molecules, which reflects spatial variations in the physical environment encountered by the tagged particle, is computed and compared with recent experimental results obtained from high resolution microscopy.