Biomimetic membranes

仿生膜

• 批准号: 298909-2012
• 负责人: Johnston, Linda
• 金额: $ 3.28万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=514784
• 关键词: Biomimetic; membranes

The cell membrane controls how cells interact with each other and with their environment, thus regulating many biological processes. Membranes are complex assemblies of hundreds of lipids and proteins and are highly organized with functional domains that have specific lipid and protein composition. As an example, membrane or lipid rafts are small, dynamic domains that have a high cholesterol and sphingolipid content and play an important role in organizing proteins for cell signaling. We study the lipid-lipid and lipid-protein/peptide interactions that control the assembly of these domains, with the long term goal of understanding membrane processes at the molecular level. We frequently use supported lipid bilayers as simplified models of natural membranes. They have a number of advantages including stability, ease of fabrication, compatibility with characterization using surface analysis methods and the ability to maintain lipid mobility and peptide/protein activity in a physiologically relevant aqueous environment. We use quantitative tools that integrate atomic force microscopy (AFM) with optical microscopy and spectroscopy to study supported bilayers and apply some of the same tools to cellular membranes. These techniques combine the ability of AFM to image individual molecules and probe molecular interactions with the ability of fluorescence to detect labeled molecules with high sensitivity and specificity and to monitor dynamics. We will study two biological problems. First, we will develop new photoreleasable-probes to control the generation of ceramide, a lipid which promotes aggregation of small membrane domains to give larger signaling platforms, and new approaches to study its bioactivity. Second, we will investigate the interaction of amyloid peptides with ordered membrane domains to understand the early stages of peptide aggregation and membrane damage that eventually lead to the neurodegeneration associated with Alzheimer's disease. Finally, we will develop new supported bilayer architectures on polymer films that are compatible with incorporation of membrane proteins for biosensing applications.

细胞膜控制着细胞之间以及细胞与环境的相互作用，从而调节许多生物过程。膜是数百种脂质和蛋白质的复杂组合，具有高度组织的功能域，具有特定的脂质和蛋白质组成。例如，膜或脂筏是小的、动态的结构域，具有高胆固醇和鞘脂含量，在组织细胞信号传导的蛋白质中起重要作用。我们研究控制这些结构域组装的脂质-脂质和脂质-蛋白/肽相互作用，以在分子水平上理解膜过程的长期目标。我们经常使用支持脂质双分子层作为天然膜的简化模型。它们具有许多优点，包括稳定性，易于制造，与使用表面分析方法进行表征的兼容性以及在生理相关的水环境中保持脂质流动性和肽/蛋白质活性的能力。我们使用原子力显微镜（AFM）与光学显微镜和光谱学相结合的定量工具来研究支撑双层，并将一些相同的工具应用于细胞膜。这些技术结合了原子力显微镜成像单个分子和探测分子相互作用的能力，以及荧光技术以高灵敏度和特异性检测标记分子和监测动力学的能力。我们将研究两个生物学问题。首先，我们将开发新的光释放探针来控制神经酰胺的产生，神经酰胺是一种促进小膜域聚集以提供更大信号平台的脂质，并开发新的方法来研究其生物活性。其次，我们将研究淀粉样肽与有序膜结构域的相互作用，以了解肽聚集和膜损伤的早期阶段，最终导致与阿尔茨海默病相关的神经变性。最后，我们将在聚合物薄膜上开发新的支持双层结构，这些结构与膜蛋白的结合兼容，用于生物传感应用。