title: The human skin barrier is organized as stacked bilayers of fully extended ceramides with cholesterol molecules associated with the ceramide sphingoid moiety.
abstract: The skin barrier is fundamental to terrestrial life and its evolution; it upholds homeostasis and protects against the environment. Skin barrier capacity is controlled by lipids that fill the extracellular space of the skin's surface layer--the stratum corneum. Here we report on the determination of the molecular organization of the skin's lipid matrix in situ, in its near-native state, using a methodological approach combining very high magnification cryo-electron microscopy (EM) of vitreous skin section defocus series, molecular modeling, and EM simulation. The lipids are organized in an arrangement not previously described in a biological system-stacked bilayers of fully extended ceramides (CERs) with cholesterol molecules associated with the CER sphingoid moiety. This arrangement rationalizes the skin's low permeability toward water and toward hydrophilic and lipophilic substances, as well as the skin barrier's robustness toward hydration and dehydration, environmental temperature and pressure changes, stretching, compression, bending, and shearing.
authors.affiliation: Department of Cell and Molecular Biology (CMB), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Iwai
authors.forename: HongMei
authors.initials: H
authors.lastname: Han
authors.forename: Lianne
authors.initials: L
authors.lastname: den Hollander
authors.forename: Stina
authors.initials: S
authors.lastname: Svensson
authors.forename: Lars-Göran
authors.initials: LG
authors.lastname: Ofverstedt
authors.forename: Jamshed
authors.initials: J
authors.lastname: Anwar
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brewer
authors.forename: Maria
authors.initials: M
authors.lastname: Bloksgaard
authors.forename: Aurelie
authors.initials: A
authors.lastname: Laloeuf
authors.forename: Daniel
authors.initials: D
authors.lastname: Nosek
authors.forename: Sergej
authors.initials: S
authors.lastname: Masich
authors.forename: Luis A
authors.initials: LA
authors.lastname: Bagatolli
authors.forename: Ulf
authors.initials: U
authors.lastname: Skoglund
authors.forename: Lars
authors.initials: L
authors.lastname: Norlén
mesh_terms: D000328:Adult; D002518:Ceramides / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D012867:Skin / Q000737:chemistry* / Q000648:ultrastructure; D013107:Sphingolipids / Q000737:chemistry*
chemical_list: D002518:Ceramides; D008051:Lipid Bilayers; D013107:Sphingolipids; D002784:Cholesterol