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Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes.
Langmuir. 2021 08 10; 37(31):9478-9489.L

Abstract

The skin barrier function is attributed to the stratum corneum (SC) intercellular lipid matrix, which is composed primarily of ceramides (CERs), free fatty acids, and cholesterol. These lipids are organized in two lamellar phases: the short and long periodicity phases (SPP and LPP), respectively. The LPP is considered important for the skin barrier function. High levels of short-chain CERs are observed in various inflammatory skin diseases and have been correlated with barrier dysfunction. In this research, we investigated how the increase in the fraction of the short-chain CER with a nonhydroxy C16 acyl chain linked to a C18 sphingosine base CER NS(C16) at the expense of the physiological chain length CER NS with a C24 acyl chain (CER NS(C24)) impacts the microstructure and barrier function of a lipid model that mimicked certain characteristics of the SC lipid organization. The permeability and lipid organization of the model membranes were compared with that of a control model without CER NS(C16). The permeability increased significantly when ≥50% of CER NS(C24) was substituted with CER NS(C16). Employing biophysical techniques, we showed that the lipid packing density reduced with an increasing proportion of CER NS(C16). Substitution of 75% of CER NS(C24) by CER NS(C16) resulted in the formation of phase-separated lipid domains and alteration of the LPP structure. Using deuterium-labeled lipids enabled simultaneous characterization of the C24 and C16 acyl chains in the lipid models, providing insight into the mechanisms underlying the reduced skin barrier function in diseased skin.

Authors+Show Affiliations

Division BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, Netherlands.Division BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, Netherlands.Division BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, Netherlands.Division BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34319754

Citation

Uche, Lorretta E., et al. "Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes." Langmuir : the ACS Journal of Surfaces and Colloids, vol. 37, no. 31, 2021, pp. 9478-9489.
Uche LE, Gooris GS, Bouwstra JA, et al. Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes. Langmuir. 2021;37(31):9478-9489.
Uche, L. E., Gooris, G. S., Bouwstra, J. A., & Beddoes, C. M. (2021). Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes. Langmuir : the ACS Journal of Surfaces and Colloids, 37(31), 9478-9489. https://doi.org/10.1021/acs.langmuir.1c01295
Uche LE, et al. Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes. Langmuir. 2021 08 10;37(31):9478-9489. PubMed PMID: 34319754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes. AU - Uche,Lorretta E, AU - Gooris,Gerrit S, AU - Bouwstra,Joke A, AU - Beddoes,Charlotte M, Y1 - 2021/07/28/ PY - 2021/7/29/pubmed PY - 2021/8/13/medline PY - 2021/7/28/entrez SP - 9478 EP - 9489 JF - Langmuir : the ACS journal of surfaces and colloids JO - Langmuir VL - 37 IS - 31 N2 - The skin barrier function is attributed to the stratum corneum (SC) intercellular lipid matrix, which is composed primarily of ceramides (CERs), free fatty acids, and cholesterol. These lipids are organized in two lamellar phases: the short and long periodicity phases (SPP and LPP), respectively. The LPP is considered important for the skin barrier function. High levels of short-chain CERs are observed in various inflammatory skin diseases and have been correlated with barrier dysfunction. In this research, we investigated how the increase in the fraction of the short-chain CER with a nonhydroxy C16 acyl chain linked to a C18 sphingosine base CER NS(C16) at the expense of the physiological chain length CER NS with a C24 acyl chain (CER NS(C24)) impacts the microstructure and barrier function of a lipid model that mimicked certain characteristics of the SC lipid organization. The permeability and lipid organization of the model membranes were compared with that of a control model without CER NS(C16). The permeability increased significantly when ≥50% of CER NS(C24) was substituted with CER NS(C16). Employing biophysical techniques, we showed that the lipid packing density reduced with an increasing proportion of CER NS(C16). Substitution of 75% of CER NS(C24) by CER NS(C16) resulted in the formation of phase-separated lipid domains and alteration of the LPP structure. Using deuterium-labeled lipids enabled simultaneous characterization of the C24 and C16 acyl chains in the lipid models, providing insight into the mechanisms underlying the reduced skin barrier function in diseased skin. SN - 1520-5827 UR - https://www.unboundmedicine.com/medline/citation/34319754/Increased_Levels_of_Short_Chain_Ceramides_Modify_the_Lipid_Organization_and_Reduce_the_Lipid_Barrier_of_Skin_Model_Membranes_ DB - PRIME DP - Unbound Medicine ER -
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