The stratum corneum comprises three layers with distinct metal-ion barrier properties
2013
The stratum corneum (SC), the horny layer of the mammalian epidermis, directly faces the external environment and protects the inner viable layers from desiccation and foreign insult. Recent findings have shown that disruption of epidermal barrier systems, for example, filaggrin deficiency, is involved in the pathogenesis of atopic diseases via augmented percutaneous sensitization with allergens that penetrate the body through the abrogated barrier of the SC1,2,3,4. Contact sensitization against small metal ions such as nickel has been associated with filaggrin deficiency, suggesting that filaggrin deficiency affects the barrier properties of the SC even against small metal ions5,6,7.
The SC consists of layers of cornified keratinocytes (corneocytes) attached to each other by corneodesmosomes, with intercellular spaces sealed with lipids. The intracellular space of corneocytes is filled with keratin filaments, filaggrin, and their degradation products2,8. Each corneocyte is encased in a “cornified envelope,” an insoluble amalgam of proteins highly cross-linked by transglutaminases, the surface of which is tightly bound to intercellular lipids, providing a barrier against the passage of water and water-soluble substances9,10.
The SC functions as an outside-in barrier against foreign insults as well as an inside-out barrier to keep skin hydrated. The insolubility of the SC and its densely packed and heavily cross-linked proteins has hampered the detailed analysis of its barrier nature by conventional imaging techniques. To overcome these difficulties, we applied imaging mass spectrometry (MS) in this study to analyze the SC. Imaging MS of biological samples allows visualization of the spatial distribution of molecules on a sample, typically a thin tissue section, by ionizing molecules from each X-Y point, then analyzing the ionized molecules and molecular ion fragments by MS and identifying them by their mass-to-charge ratio (m/z).
The SC has been considered a homogeneous barrier, and whether it consists of functionally distinct layers is unknown. Previous studies suggested that topically applied small molecules distribute more within upper layers than in lower ones; however, these results have been interpreted as a simple diffusion gradient of applied molecules within the SC11,12,13. Here, we applied imaging MS technology using time-of-flight secondary ion MS (TOF-SIMS) to analyze the SC. In contrast to previous studies using MS14,15, our improved sample preparation method and TOF-SIMS enabled us to visualize the spatial distribution of natural substances and externally applied molecules simultaneously in submicron spatial resolution. This approach revealed that the SC consists of three sharply demarcated layers with distinct barrier properties.
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