Molecular Modeling of Domain Formation upon Protein Adsorption in Lipid Bilayers

Abstract

The mechanisms that govern domain formation in phospholipid bilayers are unclear. Understanding the underlying principles of domain formation in model lipid bilayers will provide with insights on how protein adsorption leads to domain formation and also will lead to the effective design of novel biotechnology applications that can take advantage of the structure to function relationship in biology. In this work, the thermodynamics and structural properties of domain formation upon protein adsorption in model lipid membranes are studied through the application of a three dimensional molecular theory that includes a complete description of the relevant interactions of the entire phospholipid molecules. This theoretical approach takes into account the electrostatic interactions of the hydrophilic phospholipid headgroups as well as the attractive packing interactions of the phospholipid acyl tails. The proposed theory considers in an explicit manner the molecular conformations, size, shape and charge density of each molecule within a mean-field level approximation for the intermolecular interactions. The results show how domain formation in lipid bilayers depends on several biologically relevant environments such as different salt concentrations, solution pH and phospholipid composition of the bilayer, i.e. , the chemical structure and number density of the different phospholipid molecules present in the bilayer. The molecular theory provides with the tools for understanding the fundamental principles of phospholipid domain formation by giving insights on how the membrane responds to changes in its chemical environment. Moreover, since the theory includes an explicit description of the phospholipid headgroups, the coupling between the physical states of the two leaflets of the bilayer as the result of protein adsorption onto one side of the bilayer is also described.