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The Human Skin Barrier Is Organized as Stacked Bilayers of Fully Extended Ceramides with Cholesterol Molecules Associated with the Ceramide Sphingoid Moiety

Research output: Contribution to journalJournal article


  • Ichiro Iwai
  • HongMei Han
  • Lianne den Hollander
  • Stina Svensson
  • Lars-Goeran Oefverstedt
  • Jamshed Anwar
  • Jonathan Brewer
  • Maria Bloksgaard
  • Aurelie Laloeuf
  • Daniel Nosek
  • Sergej Masich
  • Luis A. Bagatolli
  • Ulf Skoglund
  • Lars Norlen
Journal publication date09/2012
JournalJournal of Investigative Dermatology
Number of pages11
Original languageEnglish


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.