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Investigation of the influence and function of different ceramide subspecies to the nanostructure and the dynamic of Stratum corneum lipid model systems

研究不同神经酰胺亚种对角质层脂质模型系统纳米结构和动力学的影响和功能

基本信息

批准号：
232323064
负责人：
Professor Dr. Gerald Brezesinski
金额：
--
依托单位：
Institut für Medizinische Physik und Biophysik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/232323064?language=en
关键词：
Investigation influence function different ceramide

项目摘要

Ceramides belong to a unique class of lipids, which differs significantly from other lipids classes. The polar head group of the ceramides are considerably less polar; the hydrophobic region is always formed by two different hydrocarbon chains, whereby one chain can be substantially longer than the other. The intercellular ceramides are essentially responsible for the barrier function of the Stratum corneum (SC). How those physico-chemically variable and dermatologically interesting lipids impact the structural organisation of the SC and therefore, the epidermal barrier is to a large extent unknown. The intended experiments will fundamentally contribute to the clarification which ceramide subclass is essential for the SC and are able to intensify the epidermal barrier. Especially the role of the polar head group of the ceramides (number and position of hydroxyl groups) will be studied. Furthermore, substances, which can be applied to enhance the penetration of drugs through this barrier, will be studied. The expertise of the work groups (WG) Huster and Brezesinski within this joint project will for the first time enable the study of the molecular dynamics of the ceramides in model bilayers (WG Huster) and allow for the investigation of the interaction of the polar head group of the ceramides with pharmaceutically relevant penetration enhancers (WG Brezesinski). This will substantially widen the knowledge of previous studies concerning the nanostructure of the ceramides and ceramide-containing SC lipid model membranes (WG Neubert). Additionally, molecular dynamic simulations (MD-Simulation) will be integrated as a theoretically method to optimally verify the experimentally received findings. For such studies both specifically deuterated as well as perdeuterated ceramides are indispensible; those have to be laboriously synthesised by the WG Dobner.

神经酰胺属于一类独特的脂质，其与其他脂质类别显著不同。神经酰胺的极性头部基团的极性相当小;疏水区域总是由两个不同的烃链形成，其中一个链可以比另一个链长得多。细胞间神经酰胺主要负责角质层（SC）的屏障功能。这些物理化学可变的和皮肤病学上有趣的脂质如何影响SC的结构组织，因此，表皮屏障在很大程度上是未知的。预期的实验将从根本上有助于澄清神经酰胺亚类是必不可少的SC，并能够加强表皮屏障。特别是神经酰胺的极性头基（羟基的数量和位置）的作用将进行研究。此外，还将研究可用于增强药物穿透这一屏障的物质。Huster工作组和Brezesinski工作组在该联合项目中的专业知识将首次使神经酰胺在模型双层中的分子动力学研究成为可能（Huster工作组），并允许研究神经酰胺的极性头部基团与药物相关渗透促进剂的相互作用（Brezesinski工作组）。这将大大拓宽以前关于神经酰胺和含神经酰胺的SC脂质模型膜（WG Neubert）的纳米结构研究的知识。此外，分子动力学模拟（MD模拟）将被整合为一种理论方法，以最佳地验证实验收到的结果。对于这样的研究，特别是氘代以及全氘代神经酰胺是必不可少的;那些必须由工作组Dobner费力地合成。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phase separation in ceramide[NP] containing lipid model membranes: neutron diffraction and solid-state NMR.

含有脂质模型膜的神经酰胺 [NP] 中的相分离：中子衍射和固态 NMR

DOI：
10.1039/c6sm02356h
发表时间：
2017
期刊：
Soft matter
影响因子：
3.4
作者：
A. Schroeter;S. Stahlberg;B. Školová;S. Sonnenberger;A. Eichner;D. Huster;K. Vávrová;T. Hauß;B. Dobner;R. H.H. Neubert;A. Vogel
通讯作者：
A. Vogel

Synthesis of specifically deuterated ceramide [AP]-C18 and its biophysical characterization using neutron diffraction.

DOI：
10.1016/j.chemphyslip.2017.02.001
发表时间：
2017-04
期刊：
Chemistry and physics of lipids
影响因子：
3.4
作者：
Stefan Sonnenberger;A. Eichner;T. Hauß;Annett Schroeter;R. Neubert;B. Dobner
通讯作者：
Stefan Sonnenberger;A. Eichner;T. Hauß;Annett Schroeter;R. Neubert;B. Dobner

The effect of non-deuterated and deuterated isopropyl myristate on the thermodynamical and structural behavior of a 2D Stratum Corneum model with Ceramide [AP].

非氘代和氘代肉豆蔻酸异丙酯对神经酰胺二维角质层模型热力学和结构行为的影响 [AP]