Towards an Understanding of Protein–Membrane Interactions: Lipid Bilayer Mechanics and Deformations in the Presence of Integral Proteins

Abstract

Plasma membranes play an essential role in cellular function and biological processes. Lipid bilayers create the boundary for cellular structures, including the membrane, internal vesicles and allow intra- and extra cellular transportation. Elastic and geometric properties of these structures are of interest in the theoretical and computational exploration of the role of membranes in cellular function. From Helfrich's work to recent curvature-tilt models, continuum approximations are often limited and overlooked, or fail to incorporate all factors that can inuence the membrane shape and function. The use of continuum models allows for the prediction and direct simulation of membrane mechanics based on material properties. Additionally, continuum models are useful to connect molecular level interactions to larger scales, allowing for the development of cellular level computational models. This work incorporates the results of all-atom molecular dynamic (MD) simulations into a curvature-stretch-tilt continuum model that accurately recreates bilayer buckling, lipid orientation, and strain. These simulations and equations allow us to determine the stretching, bending and tilt moduli of lipid bilayers, matching experimental and simulated measurements for POPC bilayers. An application of this model is in the analysis of membrane-protein interactions based on lipid bilayer mechanics, which helps in the understanding of membrane permeability and the conditions for it to happen. The findings of this research will serve as a valuable reference for future investigations into the role of lipid membranes in cellular processes.