The Stratum Corneum Revisited

Evidence for Intercellular Lipid Sequestration: Because of its loosely organized appearance in tissues subjected to routine fixation, dehydration, and embedding, the stratum corneum was not considered to be important for normal permeability barrier formation until about 35 years ago. Yet, when epidermis is frozen sectioned and the cornified envelopes of corneocytes are either swollen at alkaline pH or stained with fluorescent, lipophilic dyes, the stratum corneum appears as a compact structure with geometric, polyhedral squames arranged in vertical columns that interdigitate at their lateralmargins (1, 2). Moreover, isolated sheets of stratum corneum possess both unusually great tensile strength, and very low rates of water permeability (3). The stratum corneum is viewed currently as a layer of protein-enriched corneocytes embedded in a lipid-enriched, intercellular matrix in (4), the so-called bricks-and-mortar model (5). The evidence for such protein-lipid sequestration is based upon freeze-fracture replication, histochemical, biochemical, cell fractionation, cell separation, and physical-chemical studies (rev. in 6). Freeze-fracture reveals stacks of intercellular bilayers in the intercellular spaces, where transmission electron microscopy previously had revealed only empty spaces. Moreover, histochemical stains also display the membrane domains of the stratum corneum as enriched in neutral lipids, but only when these stains are applied to frozen sec-