Modelling the dynamic organisation of crowded and complex cell membranes: from the nano to the meso scale

Biological membranes are made up of a complex mixture of lipids and crowded with proteins, and it is becoming increasingly apparent that membranes are highly organised. Modelling the nanoscale heterogeneities within physiological membranes in molecular detail has been confounded by the inherent difficulties of simulating large numbers of proteins and multiple lipid species over meaningful timescales. I will discuss the use of coarse-grained molecular dynamics simulations to investigate diverse anionic lipid interactions with a eukaryotic potassium channel (Kir2.2) and the effect of the lipid composition on the mesoscale organisation of this channel. I will also discuss the use of coarse-grained simulations to explore how protein-protein interactions of bacterial membrane proteins affect protein organisation into ‘islands’. In order to extend length and timescales available using conventional coarse-grained molecular simulations, I have developed a ‘mesoscale’ model, which incorporates information from the bacterial membrane simulations. The mesoscale model allows validation of the simulated results with experimental single molecular tracking data, thereby combining sub-nanometre resolution structural information with dynamic data. I will further discuss how I plan to model the organisation of mitochondrial membranes and the impact of disease-state lipids.