Lipid nanotube arrays for membrane protein biochips

描述(申请人提供)：该项目的广泛目标是开发一类新的纳米级物体-底物支撑的脂质纳米管-目标是建立基于功能膜蛋白质的强大的杂交纳米设备。最近，我们的实验室证明了在一定条件下，当放置在纳米孔中时，许多磷脂可以自组装成纳米管。对于宏观上均匀且堆叠均匀的纳米孔，这些脂质纳米管形成了可用于组合分析的阵列。还发现，尽管这些膜的尺寸是纳米级的，但它们的许多性质与无支撑的双层膜的性质非常相似。因此，可以推测，脂质纳米管在支持、保护和组织功能膜蛋白方面可以作为生物膜的合适模拟物。由于生物膜和相关蛋白是最具吸引力的药物靶点，因此建议在膜蛋白生物芯片中使用脂质纳米管设计。初步结果表明，脂质纳米管阵列似乎比平面设计的衬底支撑的双层具有几个优点：比衬底的双层表面积大得多，不受表面污染的保护，以及较长的保质期。提出了以下目标。目的1-脂类纳米管的自组装：研究脂类纳米管自组装的机理，通过调控纳米孔底物的尺寸和表面性质来控制纳米管的性质；目的2-膜蛋白生物芯片：发展基于脂类纳米管阵列的蛋白质生物芯片的概念设计，能够有效地检测和分析分析物与特定的磷脂膜和膜蛋白靶标的分子相互作用。目的研究脂类纳米管中的3-膜蛋白：研究跨膜肽、膜蛋白和外周蛋白与脂类纳米管相互作用的分子机制，为进一步开发脂类纳米管生物芯片奠定基础。

DESCRIPTION (provided by applicant): The broad objective of this project is to develop a new class of nanoscale objects - substrate-supported lipid nanotubes - with the goal of building robust hybrid nanodevices that are based on functional membrane proteins. Recently, our lab demonstrated that under certain conditions many phospholipids would self assemble into a nanotube when placed inside a nanopore. For macroscopically homogeneous and uniformly stacked nanopores, these lipid nanotubes form arrays that could be used in combinatorial assays. It was also found, that despite being of a nanoscale size, many properties of these membranes are remarkably similar to those of unsupported bilayers. Thus, it is hypothesized that the lipid nanotubes may serve as suitable mimics of biomembranes in supporting, protecting, and organizing functional membrane proteins. Because biological membranes and associated proteins represent the most attractive drug targets, it is proposed to utilize lipid nanotube design in membrane protein biochips. Preliminary results indicate that the lipid nanotube arrays appear to have several advantages over substrate-supported bilayers of the planar design: much larger bilayer surface area per that of a substrate, protection from surface contaminants, and long shelf time. The following aims are proposed. Aim 1 - Self-assembly of lipid nanotubes: It is proposed to study the mechanism of the lipid nanotube self-assembly in order to gain control of the nanotube properties by manipulating the size of the nanoporous substrate and its surface properties; Aim 2 - Membrane protein biochips: To develop conceptual design of protein biochips based on lipid nanotube arrays that would efficiently detect and analyze molecular interactions of analytes with specific phospholipid membrane and membrane protein targets. Aim 3 - Membrane proteins in lipid nanotubes: To study molecular mechanisms of interaction of transmembrane peptides, membrane and peripheral proteins with the lipid nanotubes for the explicit purpose of using that information in further development of lipid nanotube biochips.