Lipid bicelles in the study of biomembrane characteristics

Abstract Simulations of lipid membranes typically make use of periodic boundary conditions to mimic macroscopically sized membranes and allow for comparison to experiments performed e.g. on planar lipid membranes or on unilamellar lipid vesicles. However, the lateral periodicity partly suppresses membrane fluctuations or membrane remodeling, processes that are of particular importance in the study of asymmetric membranes – i.e. membranes with integral or associated proteins and/or asymmetric lipid compositions. Here, we devised a simple albeit powerful lipid bicelle model system that (i) displays similar structural, dynamical and mechanical properties compared to infinite periodic lipid membrane systems, and allows (ii) for the study of asymmetric lipid bilayer systems, and (iii) the unperturbed formation of local spontaneous curvature induced by lipids or proteins in coarse-grained and all-atom molecular dynamics simulations. In addition, the system is characterized by largely unbiased thermal fluctuations as opposed to standard bilayer systems. Application of the bicelle system for an asymmetric lipid composition resembling the plasma membrane reveals that the cholesterol density for a tension-free plasma membrane with a vanishing spontaneous curvature is larger by 28% within the extracellular leaflet compared to the cytosolic leaflet. Graphical TOC Entry