Investigating the nanostructure of a CER[NP]/CER[AP]-based stratum corneum lipid matrix model: A combined neutron diffraction & molecular dynamics simulations approach

The human skin provides a physiochemical and biological protective barrier due to the unique structure of its outermost layer known as the Stratum corneum. This layer consists of corneocytes and a multi-lamellar lipid matrix forming a composite, which is a major determining factor for the barrier function of the Stratum corneum. A substantiated understanding of this barrier is necessary, as controlled breaching or modulation of the same is also essential for various health and personal care applications such as topical drug delivery and cosmetics to a name few. In this study, we discuss the state-of-the-art of neutron diffraction techniques, using specifically deuterated lipids, combined with the information obtained from molecular models using molecular dynamics simulations, to understand the structure and barrier function of the Stratum corneum lipid matrix. As an example, the effect of ceramide concentration on a lipid lamella system consisting of CER[NP]/CER [AP]/Cholesterol/free fatty acid (deprotonated) is studied. This study demonstrates the usefulness of the combined approach of neutron diffraction and molecular dynamics simulations for effective analysis of the model systems created for the Stratum corneum lipid matrix. The optimization of force fields by comparison with experimental data is furthermore an important step in the direction of providing a predictive quality.