Reproduction of a Three-Component (DPPC/DOPC/Cholesterol) Phase Diagram using Coarse Grained Molecular Dynamics

Abstract

The plasma membrane consists primarily of a mixture of lipids and proteins, responsible for creating a homeostatic environment inside the cell. The plasma membrane is also responsible for mediating cell-cell communication; specifically, membrane proteins send and receive signals across the plasma membrane. However, in some cases the membrane proteins require lipids to create a locally optimized environment to create functional groupings. Lipids may facilitate protein localization by forming phases of differing lateral organization, which proteins are likely to segregate into based on overall lipid dynamics. These phases occur mainly as liquid-disordered (Ld) or liquid-ordered (Lo); the Ld phase is composed of mainly unsaturated lipids, while the Lo phase is composed of mainly saturated lipids and cholesterol. Membranes can exist as a single fluid phase or coexistence of phases under the right compositions and conditions. It is established that phase separation can occur in certain models but the ordering progression of the single fluid phase and whether or not a threshold event occurs between the Ld and Lo phases is still largely unidentified. In this study we performed coarse-grained MARTINI molecular dynamic simulations on a ternary system, consisting of a saturated lipid, dipalmitoylphosphatidylcholine (DPPC), an unsaturated lipid, dioleoylphosphatidylcholine (DOPC), and cholesterol (CHOL). A primary goal of the study was to observe how well the MARTINI forcefield could reproduce these ternary phase diagrams. As such, no changes were made to the MARTINI forcefield, and no biases were imposed on the system. The MARTINI forcefield performed remarkably well, replicating all of the single fluid phases and most of the phase separated systems. This work were performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, Release LLNL-ABS-704312.