Biomimetic membranes

细胞膜控制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。膜是由数百种脂类和蛋白质组成的复杂集合，具有高度组织性，具有特定的脂类和蛋白质组成的功能结构域。例如，膜或脂筏是小的、动态的结构域，具有高胆固醇和神经鞘脂脂含量，并在组织蛋白质以进行细胞信号传递方面发挥重要作用。我们研究控制这些结构域组装的脂-脂和脂-蛋白/肽的相互作用，长期目标是在分子水平上了解膜过程。我们经常使用支撑型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多肽/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分子层，并将一些相同的工具应用于细胞膜。这些技术将原子力显微镜成像单个分子和探测分子相互作用的能力与荧光检测标记分子的高灵敏度和特异性以及监测动力学的能力结合在一起。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，我们将研究淀粉样多肽与有序膜结构域的相互作用，以了解多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退行性变。最后，我们将在聚合物薄膜上开发新的支持双层结构，这种结构与用于生物传感应用的膜蛋白的结合相兼容。**

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.**