Ceramides are essential constituents of the skin barrier that allow humans to live on dry land. Reduced levels of
ceramides have been associated with
skin diseases, e.g.,
atopic dermatitis. However, the structural requirements and mechanisms of action of
ceramides are not fully understood. Here, we report the effects of
ceramide acyl chain length on the permeabilities and biophysics of
lipid membranes composed of
ceramides (or free
sphingosine),
fatty acids,
cholesterol, and
cholesterol sulfate. Short-chain
ceramides increased the permeability of the
lipid membranes compared to a long-chain
ceramide with maxima at 4-6 carbons in the acyl. By a combination of differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, Langmuir monolayers, and atomic force microscopy, we found that the reason for this effect in short
ceramides was a lower proportion of tight orthorhombic packing and phase separation of continuous short
ceramide-enriched domains with shorter lamellar periodicity compared to native long
ceramides. Thus, long acyl chains in
ceramides are essential for the formation of tightly packed impermeable
lipid lamellae. Moreover, the model skin
lipid membranes are a valuable tool to study the relationships between the
lipid structure and composition,
lipid organization, and the membrane permeability.