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

皮肤脂质屏障是一种基于细胞外神经酰胺的多层脂质结构，对我们在陆地上的生存至关重要。该项目解决了脂质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。我们计划获得这些脂质纳米结构的更清晰的图像，探索蛋白质、温度和离子在脂质组装中的作用，并尝试在体外重现生理脂质重塑。我们将合成同位素标记脂质、固定化脂质、抗菌肽和脂蛋白。我们将构建已建立的和新的皮肤脂质模型，并使用生物物理方法（AFM， DSC， FTIR，拉曼显微镜，XRD，中子衍射和固态核磁共振），渗透率和失水实验，从原子细节上研究它们的性质。获得的数据将与（病理）生理皮肤脂质片的电子显微镜图像进行比较。我们的研究结果将有助于更好地了解健康和患病皮肤脂质屏障中的脂质功能。

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.