The role of ceramide chain length distribution on the barrier properties of the skin lipid membranes

Abstract

The skin barrier function is provided by the stratum corneum (SC). The lipids in the SC are composed of three lipid classes: ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs) which form two crystalline lamellar structures. In the present study, we investigate the effect of CER chain length distribution on the barrier properties of model lipid membranes mimicking the lipid composition and organization of SC. The membranes were prepared with either isolated pig CERs (PCERs) or synthetic CERs. While PCERs have a wide chain length distribution, the synthetic CERs are quite uniform in chain length. The barrier properties were examined by means of permeation studies using hydrocortisone as a model drug. Our studies revealed a reduced barrier in lipid membranes prepared with PCERs compared to synthetic CERs. Additional studies revealed that a wider chain length distribution of PCERs results in an enhanced hexagonal packing and increased conformational disordering of the lipid tails compared to synthetic CERs, while the lamellar phases did not change. This demonstrates that the chain length distribution affects the lipid barrier by reducing the lipid ordering and density within the lipid lamellae. In subsequent studies, the effect of increased levels of FFAs or CERs with a long acyl chain in the PCERs membranes was also studied. These changes in lipid composition enhanced the level of orthorhombic packing, reduced the conformational disordering and increased the barrier of the lipid membranes. In conclusion, the CER chain length distribution is an important key factor for maintaining a proper barrier.

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…The most important of such deviations are a high level of unsaturated fatty acids, shorter lipid chain lengths (Mojumdar et al, 2014;Thakoersing et al, 2013Thakoersing et al, , 2015 and an imbalance in the level of ceramide subclasses (Thakoersing et al, 2012). These changes in lipid composition are expected to contribute significantly to the impaired skin barrier of HSEs (Mojumdar et al, 2014). With respect to the bound lipid profile, this is similar to that of native human skin (Ponec et al, 2003) however, it must be stated that measurements of this profile have been conducted with a lower level of precision.…”

“…Although all lipid classes present in native human skin are also present in HSEs, there is a deviation in free lipid composition and organization compared to native human skin. The most important of such deviations are a high level of unsaturated fatty acids, shorter lipid chain lengths (Mojumdar et al, 2014;Thakoersing et al, 2013Thakoersing et al, , 2015 and an imbalance in the level of ceramide subclasses (Thakoersing et al, 2012). These changes in lipid composition are expected to contribute significantly to the impaired skin barrier of HSEs (Mojumdar et al, 2014).…”

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].…”

“…Depending on their chain lengths and headgroup architectures, the ceramides and the free fatty acids may participate in the same or in separate OR lattices [34]. Reduction of the content of free fatty acids, shortening the chain lengths of both ceramides and fatty acids and mismatch between the lipid chain lengths inhibit the formation of OR [19,33,76,92,93]. Ceramide EOS was found to stabilize the OR phases [94].…”

“…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]. …”