3D Molecular Imaging of Stratum Corneum by Mass Spectrometry Suggests Distinct Distribution of Cholesteryl Esters Compared to Other Skin Lipids

Abstract

The crucial barrier properties of the stratum corneum (SC) depend critically on the design and integrity of its layered molecular structure. However, analysis methods capable of spatially resolved molecular characterization of the SC are scarce and fraught with severe limitations, e.g., regarding molecular specificity or spatial resolution. Here, we used 3D time-of-flight secondary ion mass spectrometry to characterize the spatial distribution of skin lipids in corneocyte multilayer squams obtained by tape stripping. Depth profiles of specific skin lipids display an oscillatory behavior that is consistent with successive monitoring of individual lipid and corneocyte layers of the SC structure. Whereas the most common skin lipids, i.e., ceramides, C24:0 and C26:0 fatty acids and cholesteryl sulfate, are similarly organized, a distinct 3D distribution was observed for cholesteryl oleate, suggesting a different localization of cholesteryl esters compared to the lipid matrix separating the corneocyte layers. The possibility to monitor the composition and spatial distribution of endogenous lipids as well as active drug and cosmetic substances in individual lipid and corneocyte layers has the potential to provide important contributions to the basic understanding of barrier function and penetration in the SC.

Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts

“…The stratum corneum (SC), which provides the barrier function of the skin (Menon et al, 2012), also shows PI(4,5)P2 signal (Figure 1A). This is consistent with the notion of SC being a lipid matrix containing phospholipids (van Smeden et al, 2014a;van Smeden et al, 2014b;Sjovall et al, 2022).…”

Advancements in ToF-SIMS imaging for life sciences

“…One key advantage of ToF-SIMS in metabolomics is its versatility in detecting various metabolites, such as amino acids, lipids, sugars, and nucleotides ( Marzec et al, 2022 ; Noun et al, 2022 ; Sjövall et al, 2022 ). This capability has been demonstrated in several studies, where ToF-SIMS was applied to visualize the metabolites in different cell types and identify potential biomarkers for cell type classification, such as unsaturated diacylglycerol, oleic acid, and linoleic acid, in combination with immunofluorescence ( Song et al, 2020 ).…”

Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis

“…In the study published herein, Sjövall et al [ 100 ] have demonstrated the possibility of determining the molecular composition of superficial layers in stratum corneum, and the spatial distribution of specific lipids using three-dimensional time-of-flight secondary ion mass spectrometry. Thus, this technique could be used to expand the knowledge regarding the skin barrier, and to evaluate the effects of different active pharmaceutical ingredients, cosmetic molecules, or penetration enhancers in relation to this cutaneous function.…”