Effect of the CER[NP]:CER[AP] a ratio on the structure of a stratum corneum model lipid matrix - a molecular dynamics study

Abstract

In some dermal diseases with evident skin dehydration and desquamation, the natural ratio of CER[NP]:CER[AP] is altered in the extracellular matrix of the stratum corneum by increasing the concentration of CER[AP]. The extracellular matrix of the stratum corneum is composed of several stacked lipid bilayers. Molecular dynamics simulations were used to investigate the molecular nanostructure of CER[NP], CER[AP], cholesterol and lignoceric acid models of the extracellular matrix of the stratum corneum with a nativelike CER[NP]:CER[AP] 2:1 ratio and a CER[NP]:CER[AP] ratio of 1:2. Despite the very minor chemical difference between CER[NP] and CER[AP], which is only a single OH group, it was possible to observe differences between the structural influence of the two ceramides. In the models with 1:2 ratio, the higher CER[AP] content leads to a larger inclination of the acyl chains and a smaller overlap in the lamellar midplane, with a small increase of the repeat distance compared to the model with higher CER[NP] concentration. Because CER[AP] forms more H-bonds than CER[NP], the total number of hydrogen bonds in the headgroup region is larger in the models with higher CER[AP] concentration, reducing the mobility of the lipids towards the centre of the bilayer and resulting in less overlap and increased tilt angles.

Keywords: Ceramides; Lipid bilayers; Molecular dynamics simulation; Stratum corneum.