Engelbrecht, T.N.; Schroeter, A.; Hauß, T.; Demé, B.; Scheidt, H.A.; Huste, D.; Neubert, R.H.H.: The impact of ceramides NP and AP on the nanostructure of stratum corneum lipid bilayer. Part I: neutron diffraction and 2H NMR studies on multilamellar models based on ceramides with symmetric alkyl chain length distribution. Soft Matter 8 (2012), p. 2599-2607

We investigated the lamellar structure of ternary stratum corneum (SC) lipid model systems based on either the phytosphingosine type ceramide (CER) [NP] or CER[AP], supplemented by cholesterol and stearic acid as representative free fatty acid species. For the CER[NP] based membrane, neutron diffraction measurements revealed the coexistence of two lamellar phases, which markedly differ in their hydration properties. CER[NP] forms an extremely rigid and stable bilayer backbone and is at least partly sequestered in a separate phase which coexists with a second lamellar phase. At increased temperature, a structural re-organization of the lipids was observed. One of the lamellar phases disappeared, while the remaining phase increased its repeat distance by about 1 A#. Such a behaviour has not been described for SC lipid model membranes based on CER[AP] so far. Further, 2H NMR spectroscopic measurements on two SC lipid model systems based on either CER[NP] or CER[AP] in addition to cholesterol and perdeuterated stearic acid revealed a state of high lamellar order present in both samples, emphasizing the importance of the phytosphingosine-type ceramides for the proper formation of stable SC bilayer structures. However, the CER[NP] based ternary model showed a state of higher lamellar order than the CER[AP] based system. Our results demonstrate that slight changes in the ceramides’ head groups (CER[NP] with 3 hydroxyl groups vs. CER[AP] with 4 hydroxyl groups) have a dramatic influence on the morphology of the lipid structures 1. Introduction It is well known that the outermost layer of the mammalian skin, the stratum corneum (SC) maintains homeostasis of the organism by protecting the body from various outer influences and uncon- trolled water loss. With its intercellular lipid matrix surrounding the corneocytes, the SC is generally accepted to represent the major penetration barrier of the skin.1–3 Main constituents of the lipid lamellae are ceramides (CERs) in addition to cholesterol (CHOL) with its derivatives and free fatty acids (FFA),4,5 whereby particu- larly the structural arrangement of these SC lipids in highly ordered and coherent multiple bilayers is regarded to be essential for the maintenance of the skin barrier properties.6 The CERs represent a very lipophilic and rigid class of molecules with only small aInstitute of Pharmacy, Martin Luther University, Wolfgang-Langenbeck-Straße 4, 06120 Halle, Germany. E-mail: annett. schroeter@pharmazie.uni-halle.de; Tel: +49 345 25025 bInstitute Soft Matter and Functional Materials, Helmholtz-Zentrum- Berlin, Hahn-Meitner-Platz 1, 14109 Berlin, Germany cInstitut Laue-Langevin (ILL), 6 Rue Jules Horowitz, 38042 Grenoble Cedex 9, France dInstitute of Medical Physics and Biophysics, University of Leipzig, Ha€rtelstraße 16-18, 04107 Leipzig, Germany formed by these lipids.