Skin Barrier Fine Tuning through Low-Temperature Lipid Chain Transition.

The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC through the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32-37 °C but not at room temperature was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids (required for lipid barrier assembly) to rigid and tightly packed lipids in the mature SC (necessary for the water and permeability barriers).

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 stratum corneum lipids showed multilayer formation (approximately 10-nm step height) in an acidic but not in a neutral environment. X-ray diffraction, Fourier transform infrared spectroscopy, and permeability studies showed markedly altered lipid nanostructure and increased water loss at neutral pH compared with that at acidic pH. These findings are consistent with the data on the altered organization of skin lipids and increased transepidermal water loss under conditions such as inadequate skin acidification, for example, in neonates, the elderly, and patients with atopic dermatitis.