Very Long Chain Lipids Favor the Formation of a Homogeneous Phase in Stratum Corneum Model Membranes

Abstract

The stratum corneum (SC), the outermost layer of mammal epidermis, acts as a barrier dictating the rate of absorption of exogenous molecules through the skin, as well as to prevent excessive water loss from the body. The SC consists of protein-rich corneocytes embedded into a complex lipid mixture. The lipid fraction is mainly constituted of an equimolar mixture of ceramides (Cer), free fatty acids (FFA), and cholesterol (Chol), forming a solid phase in the intracellular space; this lipid phase is supposed to play a fundamental role in the SC barrier function. An unusual characteristic of this biological membrane is that its lipids generally bear very long acyl chains, with the 24-carbon long ones being the most abundant. In this work, we used Raman microspectroscopy and infrared spectroscopy to study the influence of the acyl chain length on the lipid mixing properties in SC model membranes. Our results revealed that the combination of ceramides and FFA bearing a very long chain is required for the formation of homogeneous lipid mixtures, while lipids with shorter chains (16-carbon and 20-carbon atom long) lead to domains with micrometer dimensions. It is proposed that the biological machinery necessary for acyl chain elongation occurring at the mammalian skin level is required to inhibit lipid phase separation, a critical feature in the proper barrier functioning.

Amino Acids and Their <i>N</i>-Acetylated Derivatives Maintain the Skin’s Barrier Function

“…Lipid efflux might be appeared to depend on lipid solubility, and the order of lipid elution from intercellular lipids is FFA, CHOL, and CER. 6) Short-chain FFAs have been found to influence the formation of hydrocarbon-chain packing structures 31) and the homogeneity of lipid membranes. 32) The proportion of PA has been reported to increase in cases of atopic eczema.…”

Distribution of Domains Formed by Lateral Packing of Intercellular Lipid in the Stratum Corneum

“…10) In addition, Raman spectroscopy was used to evaluate the planar distribution of packing structures in intercellular lipid models. [11][12][13] However, the horizontal distribution of the packing structure of intercellular lipids in the SC has not been examined.…”

Lower polyunsaturated fatty acid levels and FADS2 expression in adult compared to neonatal keratinocytes are associated with FADS2 promotor hypermethylation

“…This is believed to contribute to dryness, increased susceptibility to infection and impaired wound healing in response to injury. Although very long chain lipids are essential for creating an effective barrier [ 11 ], it is not known whether their biosynthetic machinery is affected by development or age.…”