Lipid Monolayer on Cell Surface Protein Templates Functional Extracellular Lipid Assembly.

When the ancestors of men moved from aquatic habitats to the drylands, their evolutionary strategy to restrict water loss is to seal the skin surface with lipids. It is unknown how these rigid ceramide-dominated lipids with densely packed chains squeeze through narrow extracellular spaces and how they assemble into their complex multilamellar architecture. Here it is shown that the human corneocyte lipid envelope, a monolayer of ultralong covalently bound lipids on the cell surface protein, templates the functional barrier assembly by partly fluidizing and rearranging the free extracellular lipids in its vicinity during the sculpting of a functional skin lipid barrier. The lipid envelope also maintains the fluidity of the extracellular lipids during mechanical stress. This local lipid fluidization does not compromise the permeability barrier. The results provide new testable hypotheses about epidermal homeostasis and the pathophysiology underlying diseases with impaired lipid binding to corneocytes, such as congenital ichthyosis. In a broader sense, this lipoprotein-mediated fluidization of rigid (sphingo)lipid patches may also be relevant to lipid rafts and cellular signaling events and inspire new functional materials.

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).

Cholesterol sulfate fluidizes the sterol fraction of the stratum corneum lipid phase and increases its permeability.

Desulfation of cholesterol sulfate (CholS) to cholesterol (Chol) is an important event in epidermal homeostasis and necessary for stratum corneum (SC) barrier function. The CholS/Chol ratio decreases during SC maturation but remains high in pathological conditions, such as X-linked ichthyosis, characterized by dry and scaly skin. The aim of this study was to characterize the influence of the CholS/Chol molar ratio on the structure, dynamics, and permeability of SC lipid model mixtures. We synthesized deuterated CholS and investigated lipid models with specifically deuterated components using 2H solid-state NMR spectroscopy at temperatures from 25°C to 80°C. Although the rigid acyl chains in ceramides and fatty acids remained essentially rigid upon variation of the CholS/Chol ratio, both sterols were increasingly fluidized in lipid models containing higher CholS concentrations. We also show the X-ray repeat distance of the lipid lamellar phase (105 Å) and the orthorhombic chain packing of the ceramide's acyl chains and long free fatty acids did not change upon the variation of the CholS content. However, the Chol phase separation visible in models with high Chol concentration disappeared at the 50:50 CholS/Chol ratio. This increased fluidity resulted in higher permeabilities to model markers of these SC models. These results reveal that a high CholS/Chol ratio fluidizes the sterol fraction and increases the permeability of the SC lipid phase while maintaining the lamellar lipid arrangement with an asymmetric sterol distribution.