Lipid-related barriers and gradients in the epidermis

The stratum corneum, once regarded as a degenerate, inconsequential tissue, is now respected as a structurally heterogeneous and metabolically active tissue. The segregation of lipids into intercellular domains, and the shift in composition from a mixture of polar lipids and neutral lipids to sphingolipids and neutral lipids have important implications for both barrier function and desquamation. Metabolic studies demonstrate the capacity of epidermis to synthesize lipids, the relative autonomy of such synthesis from extracutaneous influences, and the regulation of epidermal lipogenesis by local barrier requirements. Abundant lipid biosynthesis appears to occur in the stratum granulosum, consistent with the rapid recovery of barrier function following solvent treatment. Whereas nonpolar lipids, including sterol esters and hydrocarbons, provide a superficial barrier, sphingolipids and free sterols provide a more profound barrier. In parallel with the synthesis of lipids for barrier function, hydrolysis of phospholipids, glycolipids, and cholesterol sulfate occurs in the outer epidermis leading to a more hydrophobic lipid mixture with the evolution of broad membrane bilayers that may regulate both transcutaneous water loss and desquamation.