Characterisation of Coexisting Liquid Phases in Mixtures of Dipalmitoylphosphatidylcholine and Cholesterol

Abstract

Since their introduction, lipid rafts have been considered to be vital for various processes, such as membrane trafficking and signal transduction. While there is growing evidence for their existence and importance, the understanding of their emergence and physical properties is still limited.Perhaps surprisingly, the understanding of similar issues is limited also in much simpler model systems. One of the most thoroughly studied cases is the binary mixture of dipalmitoylphosphatidylcholine (DPPC) and cholesterol, which despite its simplicity shows a spectrum of phases and their coexistence regions. Even though its phase behaviour is well established, the structural and dynamic details of the nanoscale domains in the coexistence region remain largely unknown.To shed light on these features, we used atomistic molecular dynamics simulations to consider the phase behaviour of the DPPC-cholesterol system, with a focus on domain properties. Extensive simulations performed at varying temperatures and cholesterol concentrations highlighted that the experimental phase diagram was well reproduced by the atomistic simulation model. Importantly, under appropriate conditions the lipids were found to separate into two different liquid phases with clearly visible boundaries. The simulation data was used to analyse the driving forces for the formation of lipid domains, as well as their dynamics. In light of the results for this simple model system, we discuss how much can we expect to learn from related phenomena in more complex membrane systems.