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.

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM070012-09
Application #
8298544
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Lewis, Catherine D
Project Start
2004-06-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
9
Fiscal Year
2012
Total Cost
$324,950
Indirect Cost
$112,991
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Moore, Eric W; Lee, SangGap; Hickman, Steven A et al. (2009) Scanned-probe detection of electron spin resonance from a nitroxide spin probe. Proc Natl Acad Sci U S A 106:22251-6
Yazdanian, Showkat M; Hoepker, Nikolas; Kuehn, Seppe et al. (2009) Quantifying electric field gradient fluctuations over polymers using ultrasensitive cantilevers. Nano Lett 9:2273-9
Yazdanian, Showkat M; Marohn, John A; Loring, Roger F (2008) Dielectric fluctuations in force microscopy: noncontact friction and frequency jitter. J Chem Phys 128:224706
Kuehn, Seppe; Hickman, Steven A; Marohn, John A (2008) Advances in mechanical detection of magnetic resonance. J Chem Phys 128:052208
Kuehn, Seppe; Loring, Roger F; Marohn, John A (2006) Dielectric fluctuations and the origins of noncontact friction. Phys Rev Lett 96:156103
Kuehn, Seppe; Marohn, John A; Loring, Roger F (2006) Noncontact dielectric friction. J Phys Chem B 110:14525-8