Acidic pH is Required for the Multilamellar Assembly of Skin Barrier Lipids in Vitro

Lipid membrane remodeling belongs to the most fundamental processes in the body. The skin barrier lipids, which are ceramide-dominant and highly rigid, must attain an unusual multilamellar nanostructure with long periodicity to restrict water loss and prevent the entry of potentially harmful environmental factors. Our data suggest that the skin “acid mantle”, apart from regulating enzyme activities and keeping away pathogens, may also be a prerequisite for the multilamellar assembly of the skin barrier lipids. Atomic force microscopy on monolayers composed of synthetic or human SC lipids showed multilayer formation (ca 10 nm step height) in an acidic but not neutral environment. X-ray diffraction, Fourier-transform infrared spectroscopy, and permeability studies showed markedly altered lipid nanostructure and increased water loss at neutral compared to acidic pH. These findings are consistent with the altered organization of skin lipids and increased transepidermal water loss in conditions with inadequate skin acidification, e.g., in neonates, elderly, and patients with atopic dermatitis.