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Human skin barrier formation takes place via a cubic to lamellar lipid phase transition as analyzed by cryo-electron microscopy and EM-simulation
KI, Dept Med, Solna MedS, Stockholm, Sweden.;ERCO Pharma AB, Sci Life Lab, Stockholm, Sweden..
Karolinska Inst, Dept Cell & Mol Biol CMB, SE-17177 Stockholm, Sweden..
KTH, School of Engineering Sciences (SCI), Physics. KTH, Centres, SeRC - Swedish e-Science Research Centre. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-4591-9809
ERCO Pharma AB, Sci Life Lab, Stockholm, Sweden..
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2018 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 366, no 2, p. 139-151Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 366, no 2, p. 139-151
Keywords [en]
Cryo-EM, EM simulation, Skin barrier formation, Molecular dynamics
National Category
Cancer and Oncology Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-226737DOI: 10.1016/j.yexcr.2018.03.010ISI: 000429630100007PubMedID: 29567114Scopus ID: 2-s2.0-85044525984OAI: oai:DiVA.org:kth-226737DiVA, id: diva2:1209189
Funder
The Wenner-Gren FoundationSwedish Research CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180522

Available from: 2018-05-22 Created: 2018-05-22 Last updated: 2018-05-22Bibliographically approved

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Wennberg, Christian L.Lindahl, Erik

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