Behavior of Bilayer Leaflets in Asymmetric Model Membranes: Atomistic Simulation Studies

Area of Science:

• Membrane biophysics
• Computational biology
• Lipidomics

Background:

• Lipid bilayers exhibit complex spatial organization, including leaflet compositional asymmetry and lateral lipid organization, beyond the fluid mosaic model.
• Understanding interleaflet interactions is crucial for modeling biological membrane behavior.

Purpose of the Study:

• To investigate interleaflet coupling in asymmetric lipid bilayers using all-atom molecular dynamics simulations.
• To explore how phase behavior and lipid packing in one leaflet affect the apposing leaflet.

Main Methods:

• All-atom molecular dynamics simulations of symmetric and asymmetric lipid bilayers (4.1 μs total).
• Systems composed of liquid-ordered (Lo) and liquid-disordered (Ld) leaflets using a POPC/DSPC/cholesterol mixture.
• Systematic modification of lipid numbers in the Ld leaflet to simulate density fluctuations.

Main Results:

• Properties of Lo and Ld leaflets in an initially constructed asymmetric bilayer resembled those in symmetric systems.
• Modifying lipid numbers in the Ld leaflet altered its properties and those of the apposing Lo leaflet.
• Weak acyl chain interdigitation was observed but did not significantly contribute to interleaflet coupling in non-phase-separated bilayers.

Conclusions:

• Lipid packing in one leaflet influences the properties of the apposing leaflet in asymmetric lipid bilayers.
• Modulation of local density and/or curvature fluctuations via in-plane lipid packing may mediate interleaflet coupling.
• Asymmetric bilayer construction requires careful consideration beyond simply combining equilibrium structures of symmetric leaflets.