Structure-function relationship of a single double bond: the difference in lamellar phase behaviors between ceramides NS and NdS.

The barrier function of mammalian skin is closely related to the unique structure of the complex lipid matrix of the stratum corneum. Within this matrix, the heterogeneous group of ceramides plays a key role in determining barrier properties. As native stratum corneum is highly complex, simplified stratum corneum lipid mixture models can be used to efficiently elucidate their detailed structural arrangement. Here, the application of selected ceramide subspecies with defined chain lengths and head group structures in monomeric lipid mixture models, i.e. containing only a single ceramide subspecies, was found to be meaningful for a step-by-step evaluation of the distinct effects of the individual ceramide. In the present work, non-hydroxylated N-acyl chain ceramides with sphingosine and dihydrosphingosine bases with acyl chain lengths of C18, each fully protiated or partially deuterated, were obtained by chemical syntheses. As sphingosine and dihydrosphingosine-based ceramides differ just in a single double bond at the C4-C5 position of the sphingoid base, the aim of this study was to elucidate the effect of the double bond in the ceramide head groups on the lamellar phase behavior of ceramides incorporated into simplified monomeric stratum corneum lipid model membranes. The neutron diffraction studies reveled distinct differences, e.g. in unit cell dimensions with 44.1 Å for ceramide [NS] vs 46.0 Å for ceramide [NdS], with ceramide [NdS] presented a more condensed chain packing in the unit cell center. In addition, with the ceramide [NS]-d3 sample, the formation of a long phase with unit cell dimension of 75.5 Å was observed.