Beddoes Charlotte M, Gooris Gert S, Foglia Fabrizia, Ahmadi Delaram, Barlow David J, Lawrence M Jayne, Demé Bruno, Bouwstra Joke A
Division of BioTherapeutics, Leiden Academic Centre for Drug Research, University of Leiden, Einsteinweg 55, Leiden 2333 CC, The Netherlands.
Chemistry Department, Christopher Ingold Laboratories, University College London, London WC1H 0AJ, United Kingdom.
Langmuir. 2020 Sep 1;36(34):10270-10278. doi: 10.1021/acs.langmuir.0c01992. Epub 2020 Aug 20.
Understanding the structure of the stratum corneum (SC) is essential to understand the skin barrier process. The long periodicity phase (LPP) is a unique trilayer lamellar structure located in the SC. Adjustments in the composition of the lipid matrix, as in many skin abnormalities, can have severe effects on the lipid organization and barrier function. Although the location of individual lipid subclasses has been identified, the lipid conformation at these locations remains uncertain. Contrast variation experiments via small-angle neutron diffraction were used to investigate the conformation of ceramide (CER) -(tetracosanoyl)-sphingosine (NS) within both simplistic and porcine mimicking LPP models. To identify the lipid conformation of the twin chain CER NS, the chains were individually deuterated, and their scattering length profiles were calculated to identify their locations in the LPP unit cell. In the repeating trilayer unit of the LPP, the acyl chain of CER NS was located in the central and outer layers, while the sphingosine chain was located exclusively in the middle of the outer layers. Thus, for the CER NS with the acyl chain in the central layer, this demonstrates an extended conformation. Electron density distribution profiles identified that the lipid structure remains consistent regardless of the lipid's lateral packing phase, this may be partially due to the anchoring of the extended CER NS. The presented results provide a more detailed insight on the internal arrangement of the LPP lipids and how they are expected to be arranged in healthy skin.
了解角质层（SC）的结构对于理解皮肤屏障过程至关重要。长周期相（LPP）是位于角质层中的一种独特的三层板层结构。在许多皮肤异常情况下，脂质基质成分的调整会对脂质组织和屏障功能产生严重影响。尽管已确定了各个脂质亚类的位置，但这些位置的脂质构象仍不确定。通过小角中子衍射进行的对比变化实验被用于研究在简单模型和猪模拟LPP模型中神经酰胺（CER）-（二十四烷酰基）-鞘氨醇（NS）的构象。为了确定双链CER NS的脂质构象，对链进行了单独的氘代，并计算了它们的散射长度分布以确定它们在LPP晶胞中的位置。在LPP的重复三层单元中，CER NS的酰基链位于中间层和外层，而鞘氨醇链仅位于外层的中间。因此，对于酰基链位于中间层的CER NS，这表明其呈伸展构象。电子密度分布曲线表明，无论脂质的侧向堆积相如何，脂质结构都是一致的，这可能部分归因于伸展的CER NS的锚定作用。所呈现的结果为LPP脂质的内部排列以及它们在健康皮肤中的预期排列方式提供了更详细的见解。
