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Updated: Feb 12, 2026

Micropatterning Transmission Electron Microscopy Grids to Direct Cell Positioning within Whole-Cell Cryo-Electron Tomography Workflows
Published on: September 13, 2021
Human skin barrier formation takes place via a cubic to lamellar lipid phase transition as analyzed by cryo-electron
A Narangifard1, L den Hollander2, C L Wennberg3
1Department of Medicine, Solna (MedS), Karolinska Institutet (KI), Stockholm, Sweden; ERCO Pharma AB, Science for Life Laboratory, Stockholm, Sweden.
Abstract:
The skin's permeability barrier consists of stacked lipid sheets of splayed ceramides, cholesterol and free fatty acids, positioned intercellularly in the stratum corneum. We report here on the early stage of skin barrier formation taking place inside the tubuloreticular system in the secretory cells of the topmost viable epidermis and in the intercellular space between viable epidermis and stratum corneum. The barrier formation process was analysed in situ in its near-native state, using cryo-EM combined with molecular dynamics modeling and EM simulation. Stacks of lamellae appear towards the periphery of the tubuloreticular system and they are closely associated with granular regions. Only models based on a bicontinuous cubic phase organization proved compatible with the granular cryo-EM patterns. Only models based on a dehydrated lamellar phase organization agreed with the lamellar cryo-EM patterns. The data support that human skin barrier formation takes place via a cubic to lamellar lipid phase transition.
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