Liquid-Ordered Phase Formation in Cholesterol-Popc Bilayers: All-Atom Molecular Dynamics Simulations

Abstract

Cholesterol (Chol) plays an essential function in the regulation of the physical properties of the cell membrane by controlling the lipid organization and phase behavior and, thus, managing the membrane fluidity. However, at sufficiently high concentrations of Chol, the so-called liquid-ordered state is formed over a wide range of temperatures and it is characterized by high conformational order and high translational mobility. We performed a set of all-atom molecular dynamics simulations of lipid bilayers of POPC with different Chol/POPC molar ratios ranging from 0 to 50% and three different temperatures. We analyzed the behavior of the deuterium order parameter profiles of the POPC as well as its lateral diffusion. Our results show that the lipid tails become more ordered with the increase of the Chol concentration, as found in experimental results. Moreover, the predicted values of lateral diffusion are in the range of the fluid phase (D ≈ 10∧−8 - 10∧−7 cm∧2/s) in agreement with experimental ones. The observed dependences with cholesterol content and temperature are not monotonically, reflecting the phase diagram for this mixture and suggest domain formation between 15 to 40 mol %m especially for the highest temperature. It is important that the simulation is able to predict these subtle changes and opens the possibility of using them as tools for understanding the molecular effects of sterols.