Pivotal Role of Interdigitation in Interleaflet Interactions: Implications from Molecular Dynamics Simulations

Area of Science:

• Membrane biophysics
• Computational lipidomics

Background:

• Plasma membranes exhibit asymmetric lipid compositions.
• The inner leaflet's composition is often unsuitable for raft-like domain formation.
• Understanding domain stability in asymmetric membranes is crucial.

Purpose of the Study:

• Investigate the phase behavior of asymmetric lipid bilayers.
• Elucidate the conditions favoring raft-like domain formation in the inner leaflet.
• Determine the role of lipid interdigitation in membrane phase separation.

Main Methods:

• Coarse-grained molecular dynamics simulations.
• Modeling of asymmetric lipid bilayers with varying compositions.
• Analysis of lipid leaflet phase behavior and domain formation.

Main Results:

• A dioleoylphosphatidylcholine (DOPC) and cholesterol (Chol) leaflet formed liquid ordered (L_o) and liquid disordered (L_d) phases when paired with a sphingomyelin (SM)-containing leaflet.
• Interdigitated acyl chains modulated cholesterol partitioning, inducing phase separation.
• Sphingomyelin acyl chain length in the opposing leaflet influenced phase behavior.

Conclusions:

• Asymmetric membranes can exhibit raft-like domains under specific conditions.
• Lipid acyl chain interdigitation plays a critical role in modulating membrane phase behavior.
• Cholesterol partitioning and phase separation are influenced by leaflet asymmetry and lipid structure.