Fatty Acids Influence “Solid” Phase Formation in Models of Stratum Corneum Intercellular Membranes

Abstract

Stacked intercellular lipid membranes in the uppermost epidermal layer, the stratum corneum (SC), are responsible for skin's barrier function. These membranes are unique in composition, the major lipids being ceramides (Cer), cholesterol, and free fatty acids (FFA) in approximately equimolar proportions. Notably, SC lipids include chains much longer than those of most biological membranes. Previously we showed that Cer's small hydrophilic headgroup enabled SC model membranes composed of bovine brain ceramide (BBCer), cholesterol, and palmitic acid in equimolar proportion to solidify at pH 5.2. In order to determine the influence of FFA chain length on the phase behavior of such membranes, we used 2H NMR and FT-IR to study BBCer/cholesterol/FFA dispersions containing linear saturated FFA 14-22 carbons long. Independent of chain length, the solid phase dominated the FFA spectrum at physiological temperature. Upon heating, each dispersion underwent phase transitions to a liquid crystalline phase (only weakly evident for the membrane containing FFA-C22) and then to an isotropic phase. The phase behavior, the lipid mixing properties, and the transition temperatures are shown to depend strongly on FFA chain length. A distribution of FFA chain lengths is found in the SC and could be required for the coexistence of a proportion of solid lipids with some more fluid domains, which is known to be necessary for normal skin barrier function.

Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

“…S4B), similar to a neat isotropic solution of OMTS. From the present analysis, we are not able to pinpoint the location of fast isotropic solvent molecules, and we cannot distinguish between cases when the solvent is present in isotropic fluid domains within SC (11,(41)(42)(43)(44) and when it is present in an excess solution. However, we combine the studies of the molecular dynamics of the solvent molecules with an analysis of how the added solvent influences the molecular dynamics in SC lipid and protein components.…”

“…Adding more polar solvents to SC gradually leads to swelling of the corneocytes, and the solvent dynamics approaches that of the neat liquid. The addition of apolar solvents leads to an increased amount of fluid SC lipids, which also shows the characteristics of an isotropic fluid (11,(41)(42)(43). At high concentrations SC will be saturated with the solvent.…”

Skin Diseases Associated with the Depletion of Stratum Corneum Lipids and Stratum Corneum Lipid Substitution Therapy

“…The uniqueness of the organization is strongly dependent on the composition of the lipid [16] and governs the permeability and barrier properties of the SC [23,39]. …”

“…Optimum percentages of all three major classes of SC lipid are important for the formation of orthorhombic lateral packing [4,6,8,19,20,22,39,48,52,53]. A study by Norlén et al [27] indicated that as one goes deeper into the SC layers, the amount of FFA decreases, which results in an increase in transepidermal water loss (TEWL).…”

The acyl-CoA binding protein is required for normal epidermal barrier function in mice

“…Subtle changes in the permeability properties of the membranes participating in the barrier can be caused by lipid compositional changes. For example, it has been reported that the characteristic FFA composition of the stratum corneum membranes is a very important factor in promoting hydrocarbon chain mixing, defi ning lipid mixing properties and membrane stability ( 55,67 ). Similarly, the increased apparent pH detected in the stratum corneum of ACBP Ϫ / Ϫ mice may also modulate the stability of the membranes by enhancing ionization of the FAs.…”