Developing initial conditions for simulations of asymmetric membranes: a practical recommendation

Area of Science:

• Computational biophysics
• Materials science
• Soft matter physics

Background:

• Asymmetric lipid bilayers exhibit nonvanishing differential stress, complicating the generation of simulation initial conditions.
• Existing methods like individual area per lipid (APL), leaflet surface area (SA) matching, and zero differential stress (0-DS) lack a unique approach.
• A recently proposed theoretical framework provides expressions for tensions and quantifies the energetic penalty of differential stress.

Purpose of the Study:

• To introduce and validate a bilayer-based approach for generating initial conditions of asymmetric bilayers.
• To assess the impact of different generation methods on the mechanical properties of asymmetric bilayers.
• To compare simulation results with theoretical predictions for differential stress.

Main Methods:

• Developed a bilayer-based approach utilizing P21 periodic boundary conditions for partial chemical equilibrium.
• Derived theoretical expressions for bilayer tensions based on bending and area strains.
• Assessed mechanical properties (lateral pressure profile, area compressibility modulus) of asymmetric bilayers generated by APL, SA, and 0-DS methods.

Main Results:

• The bilayer-based approach with P21 boundary conditions improves agreement in mechanical properties across different generation methods.
• The surface area (SA)-based method showed the smallest changes when P21 boundary conditions were applied.
• Theoretical predictions of differential stress showed good agreement with simulation results.

Conclusions:

• Bilayer mechanical properties arise from the interplay of intrinsic bending and asymmetric lipid packing.
• The SA/P21-based approach is recommended for generating initial conditions in asymmetric bilayer simulations.
• The SA-based method is suitable when differential stress is minimal.