Cantilever Magnetic Resonance of Biomolecules

生物分子的悬臂磁共振

• 批准号: 7656136
• 负责人: JOHN A MAROHN
• 金额: $ 31.44万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7656136
• 关键词: Address; Atomic Force Microscopy; Binding; Biological; Biological Process; Biology; Biomedical Technology; Cell membrane; Cell physiology; Chemicals; Detection; Device or Instrument Development; Disease; Electron Spin Resonance Spectroscopy; Electrons; Friction; Goals; Image; In Vitro; Label; Learning; Lipid Bilayers; Location; Macromolecular Complexes; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Maps; Medicine; Microscope; Molecular; NIH Program Announcements; Nanotechnology; National Institute of Biomedical Imaging and Bioengineering; National Institute of General Medical Sciences; Noise; Nuclear Magnetic Resonance; Preparation; Property; Proteins; Protons; Research Personnel; Sampling; Scanning; Scheme; Speed; Spin Labels; Surface; Technology; Temperature; Time; Vacuum; Work; cantilever; cryogenics; density; design; electron beam lithography; experience; graduate student; improved; instrument; macromolecule; nanofabrication; nanoscale; nanoscience; nanostructured; novel strategies; public health relevance; research study; response; single molecule; three dimensional structure; tool

DESCRIPTION (provided by applicant): New tools for determining the three dimensional structure of single macromolecules and macromolecular complexes are urgently needed. The goal of this R01 renewal application is to create a "molecular microscope" capable of imaging the proton density of, or mapping the locations of electron spin labels in, a single copy of a protein or macromolecular complex. We will develop a molecular microscope capable of scanned-probe nuclear magnetic resonance (NMR) imaging and electron spin resonance (ESR) imaging. Instrument development will be directed towards the study of native and spin-labeled macromolecular complexes bound to a lipid bilayer or located in a cell membrane. Our specific aims are: (1) To exploit magnetic-tipped cantilevers and force-gradient detection of magnetic resonance to observe electron spin resonance (ESR) from a single copy of a nitroxide-labeled protein and to observe nuclear magnetic resonance (NMR) from a few hundred protons in a biomolecule; (2) To understand and mitigate (via sample preparation, cantilever design, and spin modulation schemes) excess force and force- gradient noise experienced by ultrasensitive cantilevers near surfaces in vacuum at cryogenic temperatures and to learn to prolong spin coherence time by giving more perfect spin flips in magnetic resonance force microscopy; and (3) To develop time- domain Fourier image encoding to increase the imaging speed of scanned-probe magnetic resonance. PUBLIC HEALTH RELEVANCE: New tools for determining the three dimensional structure of single macromolecules and macromolecular complexes are urgently needed. We are developing a "molecular microscope" to image nanoscale entities of relevance to biomedicine. Such an instrument would dramatically impact a broad spectrum of biological processes, disorders, and diseases.

描述（由申请人提供）：迫切需要用于确定单个大分子和大分子复合物的三维结构的新工具。 R01 更新应用的目标是创建一种“分子显微镜”，能够对蛋白质或大分子复合物的单个副本的质子密度进行成像，或绘制其中电子自旋标签的位置图。我们将开发一种能够进行扫描探针核磁共振（NMR）成像和电子自旋共振（ESR）成像的分子显微镜。仪器开发将针对与脂质双层结合或位于细胞膜中的天然和自旋标记的大分子复合物的研究。我们的具体目标是：（1）利用磁尖悬臂和磁共振力梯度检测来观察硝基氧标记蛋白质的单个副本的电子自旋共振（ESR），并观察生物分子中数百个质子的核磁共振（NMR）； （2）了解和减轻（通过样品制备、悬臂设计和自旋调制方案）超灵敏悬臂在低温下真空中表面附近所经历的过量力和力梯度噪声，并学习通过在磁共振力显微镜中提供更完美的自旋翻转来延长自旋相干时间； (3)开发时域傅里叶图像编码以提高扫描探针磁共振的成像速度。 公共卫生相关性：迫切需要用于确定单个大分子和大分子复合物的三维结构的新工具。我们正在开发一种“分子显微镜”来对与生物医学相关的纳米级实体进行成像。这样的仪器将极大地影响广泛的生物过程、紊乱和疾病。