Novel Insights into the Nanostructure of the Skin Lipid Barrier by Biophysical Methods

皮肤脂屏障是一种以神经酰胺为基础的细胞外多层脂结构，对我们在陆地上的生存至关重要。该项目致力于研究脂类组装成功能屏障的未知机制和条件，以及关键分子的确切结构和动力学。我们计划更清楚地了解这些脂类的纳米结构，探讨蛋白质、温度和离子在脂类组装中的作用，并试图在体外复制生理性的脂类重塑。我们将合成同位素标记的脂类、固定化脂类、抗菌肽和脂蛋白。我们将构建已有的和新的皮肤脂肪模型，并使用生物物理方法(AFM、DSC、FTIR、拉曼显微镜、X射线衍射、中子衍射和固体核磁共振)、渗透性和失水实验来研究其原子学性质。获得的数据将与(病理)生理性皮肤脂膜的电子显微镜图像进行比较。我们的结果将为更好地了解健康和疾病皮肤脂质屏障中的脂质功能提供依据。

The skin lipid barrier, an extracellular ceramide-based multilamellar lipid structure, is vital for our survival on dry land. This project addresses the unknown mechanisms and conditions of lipid assembly into a functional barrier and the exact structure and dynamics of crucial molecules. We plan to obtain a clearer picture of these lipids´ nanoscopic architecture, probe the role of proteins, temperature, and ions on lipid assembly, and attempt to reproduce the physiological lipid remodeling in vitro. We will synthesize isotopically labeled lipids, immobilized lipids, antimicrobial peptides, and lipoproteins. We will construct established and new skin lipid models and study their properties in atomistic detail using biophysical methods (AFM, DSC, FTIR, Raman microscopy, XRD, neutron diffraction, and solid-state NMR), permeability and water loss experiments. Obtained data will be compared to electron microscopy images of (patho) physiological skin lipid lamellae. Our results should provide a better understanding of the lipid function in healthy and diseased skin lipid barrier.