Schröter Annett, Kessner Doreen, Kiselev Mikhail A, Hauss Thomas, Dante Silva, Neubert Reinhard H H
Martin Luther Universität Halle-Wittenberg, Institute of Pharmacy, Halle (Saale), Germany.
Biophys J. 2009 Aug 19;97(4):1104-14. doi: 10.1016/j.bpj.2009.05.041.
The goal of this study was to investigate the nanostructure of SC lipid model membranes comprising the most relevant SC lipids such as the unique-structured omega-acylceramide [EOS] in a near natural ratio with neutron diffraction. In models proposed recently the presence of ceramide [EOS] and FFA are necessary for the formation of one of the two existent crystalline lamellar phases of the SC lipids, the long-periodicity phase as well as for the normal barrier function of the SC. The focus of this study was placed on the influence of the FFA BA on the membrane structure and its localization within the membrane based on the ceramides [EOS] and [AP]. The internal nanostructure of such membranes was obtained by Fourier synthesis from the experimental diffraction patterns. The resulting neutron scattering length density profiles showed that the exceptionally long ceramide [EOS] is arranged in a short-periodicity phase created by ceramide [AP] by spanning through the whole bilayer and extending even further into the adjacent bilayer. Specifically deuterated BA allowed us to determine the exact position of this FFA inside this SC lipid model membrane. Furthermore, hydration experiments showed that the presented SC mimic system shows an extremely small intermembrane hydration of approximately 1 A, consequently the headgroups of the neighboring leaflets are positioned close to each other.
本研究的目的是利用中子衍射研究包含最相关的皮肤屏障脂质(如具有独特结构的ω-酰基神经酰胺[EOS])且比例接近天然的皮肤屏障脂质模型膜的纳米结构。在最近提出的模型中,神经酰胺[EOS]和游离脂肪酸(FFA)的存在对于皮肤屏障脂质两种现存结晶层状相之一(长周期相)的形成以及皮肤屏障的正常屏障功能是必需的。本研究的重点是基于神经酰胺[EOS]和[AP],研究游离脂肪酸巴豆酸(BA)对膜结构及其在膜内定位的影响。此类膜的内部纳米结构通过对实验衍射图样进行傅里叶合成获得。所得的中子散射长度密度分布图表明,异常长的神经酰胺[EOS]通过跨越整个双层甚至进一步延伸到相邻双层,排列在由神经酰胺[AP]形成的短周期相中。特定氘代的BA使我们能够确定这种游离脂肪酸在该皮肤屏障脂质模型膜内的确切位置。此外,水合实验表明,所呈现的皮肤屏障模拟系统显示出极小的膜间水合作用,约为1埃,因此相邻小叶的头部基团彼此靠近定位。