New tools for determining the three dimensional structure of single macromolecules and macromolecular complexes are urgently needed. The goal of this R01 renewal proposal 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.
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.
|Issac, Corinne E; Gleave, Christine M; Nasr, PamÃ©la T et al. (2016) Dynamic nuclear polarization in a magnetic resonance force microscope experiment. Phys Chem Chem Phys 18:8806-19|
|Chen, Lei; Longenecker, Jonilyn G; Moore, Eric W et al. (2013) Magnetic Resonance Force Microscopy Detected Long-Lived Spin Magnetization. IEEE Trans Magn 49:3528-3532|
|Chen, Lei; Longenecker, Jonilyn G; Moore, Eric W et al. (2013) Long-lived frequency shifts observed in a magnetic resonance force microscope experiment following microwave irradiation of a nitroxide spin probe. Appl Phys Lett 102:132404|
|Alexson, Dimitri A; Hickman, Steven A; Marohn, John A et al. (2012) Single-shot nuclear magnetization recovery curves with force-gradient detection. Appl Phys Lett 101:022103|
|Lee, Sanggap; Moore, Eric W; Marohn, John A (2012) A Unified Picture of Cantilever Frequency-Shift Measurements of Magnetic Resonance. Phys Rev B Condens Matter Mater Phys 85:165447-165453|
|Longenecker, Jonilyn G; Mamin, H J; Senko, Alexander W et al. (2012) High-gradient nanomagnets on cantilevers for sensitive detection of nuclear magnetic resonance. ACS Nano 6:9637-45|
|Lee, Sanggap; Moore, Eric W; Hickman, Steven A et al. (2012) Switching through intermediate states seen in a single nickel nanorod by cantilever magnetometry. J Appl Phys 111:83911-839117|
|Longenecker, Jonilyn G; Moore, Eric W; Marohn, John A (2011) Rapid serial prototyping of magnet-tipped attonewton-sensitivity cantilevers by focused ion beam manipulation. J Vac Sci Technol B Nanotechnol Microelectron 29:32001|
|Moore, Eric W; Lee, Sanggap; Hickman, Steven A et al. (2010) Evading surface and detector frequency noise in harmonic oscillator measurements of force gradients. Appl Phys Lett 97:|
|Hickman, Steven A; Moore, Eric W; Lee, SangGap et al. (2010) Batch-fabrication of cantilevered magnets on attonewton-sensitivity mechanical oscillators for scanned-probe nanoscale magnetic resonance imaging. ACS Nano 4:7141-50|
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