Effects of sphingomyelin/ceramide ratio on the permeability and microstructure of model stratum corneum lipid membranes

Abstract

The conversion of sphingomyelin (SM) to a ceramide (Cer) by acid sphingomyelinase (aSMase) is an important event in skin barrier development. A deficiency in aSMase in diseases such as Niemann-Pick disease and atopic dermatitis coincides with impaired skin barrier recovery after disruption. We studied how an increased SM/Cer ratio influences the barrier function and microstructure of model stratum corneum (SC) lipid membranes. In the membranes composed of isolated human SC Cer (hCer)/cholesterol/free fatty acids/cholesteryl sulfate, partial or full replacement of hCer by SM increased water loss. Partial replacement of 25% and 50% of hCer by SM also increased the membrane permeability to theophylline and alternating electric current, while a higher SM content either did not alter or even decreased the membrane permeability. In contrast, in a simple membrane model with only one type of Cer (nonhydroxyacyl sphingosine, CerNS), an increased SM/Cer ratio provided a similar or better barrier against the permeation of various markers. X-ray powder diffraction revealed that the replacement of hCer by SM interferes with the formation of the long periodicity lamellar phase with a repeat distance of d=12.7nm. Our results suggest that SM-to-Cer processing in the human epidermis is essential for preventing excessive water loss, while the permeability barrier to exogenous compounds is less sensitive to the presence of sphingomyelin.

First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis

“…However, statistical significance for HILIC-identified metabolites was lost after FWER adjustment. PC and PE are lipids known to enhance barrier function, provide direct and indirect protection against S. aureus, and modulate skin immunity (17,(31)(32)(33)(34). Furthermore, while the bioactivities of PC and PE with these specific acyl chains have not been assessed, recent studies have demonstrated that abnormalities in skin lipid content and metabolism are strongly associated with AD (35,36).…”

The physical chemistry of the stratum corneum lipids

“…hexagonal and orthorhombic, respectively) [75]. In vivo and in vitro studies of diseased and healthy SC have also demonstrated a direct correlation between the lipid chain length and the packing density and repeat distance in the resulting lipid phases; the relative content of the different ceramides classes also influences the molecular organization of the lipid lamellae [76][77][78][79][80]. As another example, the geometry and content of the lipid phases in samples of identical composition prepared in the exact same way except for a difference in the equilibration temperature of only 10°C are radically different [81].…”

“…Several studies have given indications that the lipid organization in the direction normal to the skin surface (i.e. the lamellar organization) also plays an important role in regulating the barrier efficiency [76,80,102]. …”

Comprehensive mapping of human body skin hydration: A pilot study

“…CERs are traditionally described as the “cement” that joins the corneocytes to form the SC wall over the epidermis; thus, they are pivotal for control of water loss in the skin. Actually, some studies have suggested that an abnormality in the CERs profile reflects impairment in SC functions, such hydration . In this regard, it has been demonstrated that regions of lower hydration have a lower amount of total CERs, evidenced in regions such as scalp, forehead, cheek, lip, upper arm, back of the hand, palm of the hand, finger, buttock, and lower leg .…”