How Tolerant are Membrane Simulations with Mismatch in Area per Lipid between Leaflets?

Area of Science:

• Biophysics
• Computational Biology
• Materials Science

Background:

• Estimating lipid numbers in complex bilayer membranes is challenging.
• Lipid packing mismatches (area per lipid) can alter leaflet lateral pressure.

Purpose of the Study:

• Investigate the impact of lipid packing mismatch on bilayer properties.
• Determine allowable mismatch thresholds for accurate membrane simulations.

Main Methods:

• Molecular dynamics simulations of lipid bilayers with varying lipid number mismatches.
• Inclusion of peptides (gramicidin A, WALP23) to assess their influence.
• Analysis of bilayer properties including order, surface tension, and curvature energetics.

Main Results:

• Simulations remained stable, but mismatch induced asymmetric lipid packing (ordered upper, less ordered lower leaflet).
• Impacts were mild up to 5-10% mismatch; saturated lipids were more sensitive than unsaturated ones.
• Bilayer energetics indicated instability with significant mismatch.

Conclusions:

• A quantitative criterion for allowable mismatch was proposed based on continuum elastic models.
• Area per lipid mismatches up to 5% are likely tolerable for typical all-atom membrane simulations (40-160 lipids/leaflet).