Phase Diagram of a Stratum Corneum Lipid Mixture. 2018

Maren Podewitz, and Yin Wang, and Paraskevi Gkeka, and Susanne von Grafenstein, and Klaus R Liedl, and Zoe Cournia
Institute of General, Inorganic and Theoretical Chemistry, and Center for Molecular Biosciences Innsbruck (CMBI) , University of Innsbruck , Innrain 80-82 , A-6020 Innsbruck , Austria.

Computational modeling of lipid ternary mixtures is challenging because of their complicated and segmented phase diagram, the long timescales required for mixing the system components, and the necessity to sufficiently sample the three-dimensional phase space. Here, we investigate a ternary system, which mimics the lipid matrix of the stratum corneum, the outermost layer of the epidermis and the primary barrier for transdermal drug absorption. Our system consists of ceramide, cholesterol, and lignoceric acid at 23 different composition ratios, which we study at two different temperatures using coarse-grained molecular dynamics (CG MD) simulations. As CG MD simulations heavily depend on the choice of parameters, first an improved set of ceramide CG parameters was developed that reproduces experimental and all-atom simulation data. Second, the performance of the recently updated MARTINI 2015 cholesterol force field was systematically evaluated and compared to the 2007 model. We provide a detailed analysis of the structural and dynamic properties of the ternary system, such as area per lipid, area compressibility modulus, lipid order parameters, bilayer thickness, lipid tail interdigitation, and lateral self-diffusion. Based on the analysis of these properties, we devise a phase diagram of the ternary system, where three different phases, namely, liquid-disordered, gel, and liquid-ordered, are observed. The individual occurrence of a certain phase not only depends on the component molar ratio and the temperature but also decisively on the employed cholesterol force field.

UI MeSH Term Description Entries
D008051 Lipid Bilayers Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D002518 Ceramides Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE. Ceramide
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004058 Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT. Diffusions
D004817 Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics

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