title: DPPC-cholesterol phase diagram using coarse-grained Molecular Dynamics simulations.
abstract: Cholesterol-phospholipid bilayers continue to be the current state of the art in membrane models and serve as representative systems for studying the effect of cholesterol on the cell membrane. As the mixing of different lipid species requires long spatio-temporal scales, coarse-grained models have gained increasing popularity in modeling such membrane systems. In this paper, a systematic study of the MARTINI coarse-grained model for the DPPC-cholesterol binary system has been performed. We construct the phase diagram of DPPC lipid bilayers in the presence of different cholesterol concentrations and at different temperatures using coarse-grained Molecular Dynamics (MD) simulations with the MARTINI force field. The phase diagram based on the condensation effect is directly comparable to available experimental data and demonstrates qualitative agreement over all cholesterol concentrations. Self-assembled bilayers quantitatively reproduce experimental observables, such as lateral diffusion of lipids, electron density, area per lipid and lipid order parameters. The phase diagram of the DPPC-cholesterol binary system also reveals the profound effect of cholesterol on the physical properties of phospholipid bilayers such lipid order, diffusion, and fluidity. Cholesterol induces the liquid-ordered phase, which increases the fluidity of the phospholipid hydrocarbon chains above the gel to liquid-crystalline phase transition temperature and decreases it below the phase transition. The present study suggests that the MARTINI force field can be successfully used to obtain molecular level insights into cholesterol-DPPC model membranes.
authors.affiliation: Department of Theoretical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, Austria.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 11527, Athens, Greece.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Gkeka
authors.affiliation: Department of Theoretical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, Austria.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Fuchs
authors.affiliation: Department of Theoretical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, Austria. Electronic address: klaus.liedl@uibk.ac.at.
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Liedl
authors.affiliation: Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 11527, Athens, Greece. Electronic address: zcournia@bioacademy.gr.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Cournia
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D004058:Diffusion; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D044367:Phase Transition; D013696:Temperature; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol
keywords: Cholesterol; Coarse-grained simulations; DPPC; Lipid bilayer; MARTINI force field; Membrane; Molecular dynamics; Phase diagram; Phase transition