Lipid nanotube arrays for membrane protein biochips

用于膜蛋白生物芯片的脂质纳米管阵列

• 批准号: 7350191
• 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
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7350191
• 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

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）：该项目的总体目标是开发一类新型纳米级物体——基底支撑的脂质纳米管——其目标是构建基于功能性膜蛋白的稳健的混合纳米器件。最近，我们的实验室证明，在某些条件下，当放置在纳米孔内时，许多磷脂会自组装成纳米管。对于宏观上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。研究还发现，尽管这些膜具有纳米级尺寸，但其许多特性与无支撑双层膜的特性非常相似。因此，推测脂质纳米管可以作为生物膜的合适模拟物来支持、保护和组织功能性膜蛋白。由于生物膜和相关蛋白代表了最具吸引力的药物靶点，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基底支撑双层具有几个优点：每个基底的双层表面积大得多、免受表面污染物的影响以及较长的保存时间。提出以下目标。目标1——脂质纳米管的自组装：建议研究脂质纳米管自组装的机制，以便通过操纵纳米多孔基底的尺寸及其表面性质来控制纳米管的性质；目标 2 - 膜蛋白生物芯片：开发基于脂质纳米管阵列的蛋白质生物芯片的概念设计，该芯片将有效检测和分析分析物与特定磷脂膜和膜蛋白靶标的分子相互作用。目标 3 - 脂质纳米管中的膜蛋白：研究跨膜肽、膜和外周蛋白与脂质纳米管相互作用的分子机制，以明确利用该信息进一步开发脂质纳米管生物芯片。

项目成果

Flow-through lipid nanotube arrays for structure-function studies of membrane proteins by solid-state NMR spectroscopy.

流通式脂质纳米管阵列，用于通过固态核磁共振波谱研究膜蛋白的结构功能。

• DOI: 10.1529/biophysj.106.085191
• 发表时间: 2006-10-15
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: E. Chekmenev;P. Gor’kov;T. Cross;A. Alaouie;A. Smirnov
• 通讯作者: A. Smirnov

Spin-labeled pH-sensitive phospholipids for interfacial pKa determination: synthesis and characterization in aqueous and micellar solutions.

用于界面 pKa 测定的自旋标记 pH 敏感磷脂：水溶液和胶束溶液中的合成和表征。

• 发表时间: 2009-03-19
• 作者: Voinov, Maxim A;Kirilyuk, Igor A;Smirnov, Alex I
• 通讯作者: Smirnov, Alex I

Microfluidic Channels on Nanopatterned Substrates: Monitoring Protein Binding to Lipid Bilayers with Surface-Enhanced Raman Spectroscopy.

纳米图案基底上的微流体通道：利用表面增强拉曼光谱监测蛋白质与脂质双层的结合。

• 发表时间: 2010-04-01
• 影响因子: 2.8
• 作者: Banerjee, Amrita;Perez;Hahn, D;Smirnov, Alex I;Grebel, H
• 通讯作者: Grebel, H

Geometry of hydrogen bonds formed by lipid bilayer nitroxide probes: a high-frequency pulsed ENDOR/EPR study.

脂质双层硝基氧探针形成的氢键的几何形状：高频脉冲 ENDOR/EPR 研究。

• 发表时间: 2007-03-28
• 影响因子: 15
• 作者: Smirnova, Tatyana I;Smirnov, Alex I;Paschenko, Serguei V;Poluektov, Oleg G
• 通讯作者: Poluektov, Oleg G

Local polarity and hydrogen bonding inside the Sec14p phospholipid-binding cavity: high-field multi-frequency electron paramagnetic resonance studies.

Sec14p 磷脂结合腔内的局部极性和氢键：高场多频电子顺磁共振研究。

• 发表时间: 2007-05-15
• 影响因子: 3.4
• 作者: Smirnova, Tatyana I;Chadwick, Thomas G;Voinov, Maxim A;Poluektov, Oleg;van Tol, Johan;Ozarowski, Andrzej;Schaaf, Gabriel;Ryan, Margaret M;Bankaitis, Vytas A
• 通讯作者: Bankaitis, Vytas A