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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571520
• 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.

细胞膜控制着细胞如何相互作用以及与环境的相互作用，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装体，并且高度组织有具有特定脂质和蛋白质组成的功能结构域。例如，膜筏或脂筏是小的动态结构域，其具有高胆固醇和鞘脂含量，并且在组织蛋白质用于细胞信号传导中起重要作用。我们研究了控制这些结构域组装的脂质-脂质和脂质-蛋白质/肽相互作用，长期目标是在分子水平上了解膜过程。我们经常使用支持的脂质双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的表征的相容性以及在生理学相关的水性环境中保持脂质流动性和肽/蛋白质活性的能力。我们使用定量的工具，集成原子力显微镜（AFM）与光学显微镜和光谱学研究支持双层，并将一些相同的工具，细胞膜。这些技术联合收割机将AFM成像单个分子和探测分子相互作用的能力与荧光以高灵敏度和特异性检测标记分子并监测动力学的能力相结合。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结构域聚集以提供更大信号平台的脂质，以及研究其生物活性的新方法。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，我们将开发新的支持双层结构的聚合物薄膜，是兼容的膜蛋白的生物传感应用。