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The importance of ceramide headgroup for lipid localisation in skin lipid models.
Biochim Biophys Acta Biomembr. 2022 06 01; 1864(6):183886.BB

Abstract

The stratum corneum's lipid matrix is a critical for the skin's barrier function and is primarily composed of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The lipids form a long periodicity phase (LPP), a unique trilayer unit cell structure. An enzyme driven pathway is implemented to synthesize these key lipids. If these enzymes are down- or upregulated as in inflammatory diseases, the final lipid composition is affected often altering the barrier function. In this study, we mimicked down regulation of enzymes involved in the synthesis of the sphingosine and CER amide bond. In a LPP lipid model, we substituted CER N-(tetracosanoyl)-sphingosine (CER NS) with either i) FFA C24 and free sphingosine, to simulate the loss of the CER amide bond, or ii) with FFA C24 and C18 to simulate the loss of the sphingosine headgroup. Our study shows the lipids in the LPP would not phase separate until at least 25% of the CER NS is substituted keeping the lateral packing and conformational ordering unaltered. Neutron diffraction studies showed that free sphingosine chains localized at the outer layers of the unit cell, while the remaining CER NS head group was concentrated in the inner headgroup layers. However, when FFA C18 was inserted, CER NS was dispersed throughout the LPP, resulting in an even distribution between the inner and outer water layers. The presented results highlight the importance of the CER NS headgroup structure and its interaction in combination with the carbon chain invariability for optimal lipid arrangement.

Authors+Show Affiliations

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, University of Leiden, Leiden, the Netherlands.Division of BioTherapeutics, Leiden Academic Centre for Drug Research, University of Leiden, Leiden, the Netherlands.Division of Pharmacy and Optometry, Manchester University, Manchester, United Kingdom.Division of Pharmacy and Optometry, Manchester University, Manchester, United Kingdom.ISIS Neutron and Muon Source, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX, United Kingdom.ALBA Synchrotron, Carrer de la Llum 2-6, 08290 Cerdanyola del Valles, Barcelona, Spain.Institut Laue-Langevin, Grenoble, France.Division of BioTherapeutics, Leiden Academic Centre for Drug Research, University of Leiden, Leiden, the Netherlands. Electronic address: bouwstra@chem.leidenuniv.nl.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35143742

Citation

Beddoes, Charlotte M., et al. "The Importance of Ceramide Headgroup for Lipid Localisation in Skin Lipid Models." Biochimica Et Biophysica Acta. Biomembranes, vol. 1864, no. 6, 2022, p. 183886.
Beddoes CM, Gooris GS, Barlow DJ, et al. The importance of ceramide headgroup for lipid localisation in skin lipid models. Biochim Biophys Acta Biomembr. 2022;1864(6):183886.
Beddoes, C. M., Gooris, G. S., Barlow, D. J., Lawrence, M. J., Dalgliesh, R. M., Malfois, M., Demé, B., & Bouwstra, J. A. (2022). The importance of ceramide headgroup for lipid localisation in skin lipid models. Biochimica Et Biophysica Acta. Biomembranes, 1864(6), 183886. https://doi.org/10.1016/j.bbamem.2022.183886
Beddoes CM, et al. The Importance of Ceramide Headgroup for Lipid Localisation in Skin Lipid Models. Biochim Biophys Acta Biomembr. 2022 06 1;1864(6):183886. PubMed PMID: 35143742.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The importance of ceramide headgroup for lipid localisation in skin lipid models. AU - Beddoes,Charlotte M, AU - Gooris,Gert S, AU - Barlow,David J, AU - Lawrence,M Jayne, AU - Dalgliesh,Robert M, AU - Malfois,Marc, AU - Demé,Bruno, AU - Bouwstra,Joke A, Y1 - 2022/02/07/ PY - 2021/12/23/received PY - 2022/02/01/revised PY - 2022/02/02/accepted PY - 2022/2/11/pubmed PY - 2022/2/11/medline PY - 2022/2/10/entrez SP - 183886 EP - 183886 JF - Biochimica et biophysica acta. Biomembranes JO - Biochim Biophys Acta Biomembr VL - 1864 IS - 6 N2 - The stratum corneum's lipid matrix is a critical for the skin's barrier function and is primarily composed of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The lipids form a long periodicity phase (LPP), a unique trilayer unit cell structure. An enzyme driven pathway is implemented to synthesize these key lipids. If these enzymes are down- or upregulated as in inflammatory diseases, the final lipid composition is affected often altering the barrier function. In this study, we mimicked down regulation of enzymes involved in the synthesis of the sphingosine and CER amide bond. In a LPP lipid model, we substituted CER N-(tetracosanoyl)-sphingosine (CER NS) with either i) FFA C24 and free sphingosine, to simulate the loss of the CER amide bond, or ii) with FFA C24 and C18 to simulate the loss of the sphingosine headgroup. Our study shows the lipids in the LPP would not phase separate until at least 25% of the CER NS is substituted keeping the lateral packing and conformational ordering unaltered. Neutron diffraction studies showed that free sphingosine chains localized at the outer layers of the unit cell, while the remaining CER NS head group was concentrated in the inner headgroup layers. However, when FFA C18 was inserted, CER NS was dispersed throughout the LPP, resulting in an even distribution between the inner and outer water layers. The presented results highlight the importance of the CER NS headgroup structure and its interaction in combination with the carbon chain invariability for optimal lipid arrangement. SN - 1879-2642 UR - https://www.unboundmedicine.com/medline/citation/35143742/The_importance_of_ceramide_headgroup_for_lipid_localisation_in_skin_lipid_models_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0005-2736(22)00028-1 DB - PRIME DP - Unbound Medicine ER -