Off-lattice model for the phase behavior of lipid-cholesterol bilayers

Area of Science:

• Biophysics
• Materials Science
• Computational Chemistry

Background:

• Lipid bilayers exhibit coupled order-disorder processes in chain packing and conformation.
• Cholesterol's role in altering these processes and forming the liquid-ordered phase is experimentally observed but lacks a complete microscopic explanation.

Purpose of the Study:

• To develop a microscopic model explaining cholesterol's decoupling effect on lipid bilayer ordering.
• To generate a phase diagram consistent with experimental observations of lipid-cholesterol mixtures.
• To characterize the distinct structure of the liquid-ordered phase.

Main Methods:

• An off-lattice microscopic model using a 2D random triangulation algorithm.
• Representation of lipid and cholesterol molecules as hard-core particles with internal degrees of freedom and nearest-neighbor interactions.
• Monte Carlo simulations, including histogram reweighting, thermodynamic reweighting, finite-size scaling, and non-Boltzmann sampling.

Main Results:

• The model successfully describes the decoupling of lipid-chain packing and conformational ordering due to cholesterol.
• A phase diagram consistent with experimental data for phospholipid-cholesterol mixtures was generated.
• A unique small-scale structure of the liquid-ordered phase was identified and characterized.

Conclusions:

• The study provides a consistent microscopic interpretation of phospholipid-cholesterol mixture phases based on cholesterol's dual action.
• The developed model offers a promising framework for a unifying description of various lipid-sterol mixtures.
• The findings deepen the understanding of membrane biophysics and the role of sterols in biological systems.