title: Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails.
abstract: Ceramides are indispensable constituents of the stratum corneum (SC), the uppermost impermeable layer of human skin. Ceramides with shorter (four- to eight-carbon acyl chains) fatty acid chains increase skin and model membrane permeability, while further shortening of the chain leads to increased resistance to penetration almost as good as that of ceramides from healthy skin (24 carbons long on average). Here we address the extent to which the atomistic CHARMM36 and coarse-grain MARTINI molecular dynamics (MD) simulations reflect the skin permeability data. As a result, we observed the same bell-shaped permeability trend for water that was observed in the skin and multilayer membrane experiments for model compounds. We showed that the enhanced permeability of the short ceramides is mainly caused by the disturbance of their headgroup conformation because of their inability to accommodate the shorter lipid acyl chain into a typical hairpin conformation, which further led to their destabilization and phase separation. As MD simulations described well delicate structural features of SC membranes, they seem to be suitable for further studies of the SC superstructure, including the development of skin penetration enhancers for transdermal drug delivery and skin toxicity risk assessment studies.
authors.affiliation: †Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, tř. 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Paloncýová
authors.affiliation: ‡Skin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Vávrová
authors.affiliation: †Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, tř. 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Žofie
authors.initials: Ž
authors.lastname: Sovová
authors.forename: Russell
authors.initials: R
authors.lastname: DeVane
authors.affiliation: †Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, tř. 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka
authors.affiliation: †Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, tř. 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Berka
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002518:Ceramides / Q000737:chemistry* / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010539:Permeability; D014867:Water / Q000378:metabolism
chemical_list: D002518:Ceramides; D008051:Lipid Bilayers; D014867:Water