Lipid nanotube arrays for membrane protein biochips

用于膜蛋白生物芯片的脂质纳米管阵列

基本信息

批准号：
7174700
负责人：
ALEX I. SMIRNOV
金额：
$ 24.3万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-01 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7174700
关键词：
Aluminum Oxide Area Bacterial Reaction Center Protein Benchmarking Binding Biochemical Biological Biological Assay Biological Models Buffers Caliber Cartoons Cells Charge Chemistry Cholesterol Class Complex Condition Deposition Detection Development Diffusion Drug Delivery Systems Elements Energy Transfer Event Figs - dietary Film Fluorescence Fluorescence Microscopy Goals Head Humidity Hybrids Image Individual Intake Knowledge Lateral Length Life Life Cycle Stages Lipids Liposomes Maps Measurement Membrane Membrane Proteins Methods Modeling Molecular Molecular Conformation Monitor Nanotubes Optical Methods Optics Pattern Peptides Peripheral Pharmaceutical Preparations Phase Phospholipids Play Process Property Protein Binding Protein Microchips Proteins Proteome Purpose Range Reaction Reading Reporting Research Role Screening procedure Signal Transduction Silanes Solid Structure Study models Surface Surface Plasmon Resonance Surface Properties Techniques Technology Temperature Time Tube Vesicle base biochip combinatorial cost design drug development electrical property functional group interest nanodevice nanopore nanoscale programs protein protein interaction research study self assembly silane size two-photon

项目摘要

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.

描述（由申请人提供）：该项目的广泛目的是开发一类新的纳米级对象 - 基板支撑的脂质纳米管 - 旨在构建基于功能性膜蛋白的强大混合纳米置换剂。最近，我们的实验室证明，在某些条件下，将许多磷脂放置在纳米孔中时，许多磷脂会自我组装成纳米管。对于宏观均匀且均匀堆叠的纳米孔，这些脂质纳米管形成可用于组合测定的阵列。还发现，尽管具有纳米级的大小，但这些膜的许多特性与不支持双层的膜非常相似。因此，假设脂质纳米管可以用作支持，保护和组织功能性膜蛋白的生物膜的合适模拟。由于生物膜和相关蛋白是最有吸引力的药物靶标，因此建议在膜蛋白生物芯片中利用脂质纳米管设计。初步结果表明，脂质纳米管阵列似乎比平面设计的底物支持的双层具有多个优点：根据基材的较大的双层表面积，可免受表面污染物的保护，并具有较长的货架时间。提出了以下目标。目的1-脂质纳米管的自组装：提议研究脂质纳米管的机制自组装，以通过操纵纳米多孔底物及其表面特性的大小来控制对纳米管性能的控制； AIM 2-膜蛋白生物芯片：基于脂质纳米管阵列开发蛋白质生物芯片的概念设计，该阵列将有效地检测和分析分析物与特定磷脂膜和膜蛋白靶标的分析物的分子相互作用。 AIM 3-脂质纳米管中的膜蛋白：研究跨膜肽，膜和周围蛋白与脂质纳米管相互作用的分子机制，以实现在脂质纳米管生物的进一步发展中使用该信息的明确目的。