pH, Cholesterol Sulfate, and Fatty Acids Affect the Stratum Corneum Lipid Organization

Abstract

Lipid mixtures prepared from cholesterol (CHOL), isolated ceramides (CER), and free fatty acids can serve as attractive tools to study the role various stratum corneum (SC) lipids or microenvironmental conditions play in the SC lipid organization, as the phase behavior in these mixtures and in SC are similar: two lamellar phases with periodicities of approximately 6 and 13 nm are present. Because pH and cholesterol sulfate (CSO4) gradients exist in SC and may affect the local SC lipid organization, the effects of pH and CSO4 on lipid phase behavior was examined. X-ray diffraction studies with CHOL:CER mixtures revealed that the lamellar ordering at pH 5 and 7.4 were similar: both the short and the long periodicity phases were present. Upon addition of free fatty acids the phase behavior became pH dependent; the long periodicity phase being more dominant at pH 7.4 than at pH 5. Similar observations have been made upon addition of CSO4. Furthermore, only in the presence of CSO4 did phase-separated CHOL disappear, indicating that CHOL completely dissolves in the lamellar phases. A major phase change from an hexagonal to an orthorhombic lateral packing has been observed in the presence of free fatty acids. Furthermore, in the presence of CSO4 next to orthorhombic also liquid lateral packing could be detected. In contrast to lamellar ordering, changes in pH did not affect the lateral packing in any of the lipid mixtures studied.

Neonatal Development of the Stratum Corneum pH Gradient: Localization and Mechanisms Leading to Emergence of Optimal Barrier Function

“…Further, based on the pKa of the predominant SC FFA (Lieckfeldt et al, 1995;Kanicky et al, 2000), it is not yet evident how a pH as acidic as present in the SC could be produced by this pathway alone. The PL-to-FFA mechanism is also complicated by the prospect that acidity is needed to incorporate FFA into the lipid bilaycr system, rather than acidity being supplied through FFA (Bouwstra et al, 1998;Lieckfeldt et al, 1995;Bouwstra et al, 2000). Together, these data suggest that the extent to which PL-derived FFA participate in neonatal SC acidification remains unresolved.…”

NHE1 Regulates the Stratum Corneum Permeability Barrier Homeostasis

“…For topical inhibitor applications, solutions of HEPES buffer (10 mM) at either pH 7.4 or 5.5, contained either amiloride (5 M), HOE694 (7.5 M), or buffer alone. The inhibitor-concentrations were chosen in the range of the published 50% inhibitory concentrations (IC 50 ) for NHE1 inhibitory compounds in fibroblasts (22,23).…”

“…We compared the effects of amiloride as the prototypical NHE inhibitor (27,28) with the highly specific NHE1 inhibitor HOE694 (29) at various doses on permeability barrier homeostasis. When amiloride was applied after tape-stripping in a concentration range, based upon its reported IC 50 …”

Cholesterol sulfate in human physiology: what's it all about?

“…Substantial evidence has accumulated demonstrating an important role for cholesterol sulfate in keratinocyte differentiation and development of the barrier (26,(111)(112)(113). Cholesterol sulfate formation occurs early on in human squamous development, suggesting a functional role at an early stage in differentiation (28).…”

“…In addition to desmosomes, which form junctions between adjacent cells and are involved in adhesion of corneocytes, lipid bilayers play a role in intercellular cohesion in the stratum corneum, and a decrease in cholesterol sulfate content can affect the stratum corneum lipid phase behavior (113). A reduction in cholesterol sulfate content in the stratum corneum decreases the stability of bilayers and reduces the fraction of lipids arranged in liquid lateral packing, which results in a reduction in the elasticity of the lipid phases, preventing proper corneocyte lipid lamellae orientation (113,123). The end result is a decrease in cohesion between cells and the promotion of cell shedding or desquamation.…”