The observation of spectroscopic signals in response to mechanically induced changes in biological macromolecules can be enabled at an unprecedented level of resolution by coupling single-molecule manipulation/sensing using carbon nanotubes with single-molecule fluorescence imaging. Proteins, DNA and other biomolecules can be attached to nanotubes to give highly specific single-molecule probes for the investigation of intermolecular dynamics, the assembly of hybrid biological and nanoscale materials and the development of molecular electronics. Recent advances in nanotube fabrication and Atomic Force Microscope (AFM) imaging with nanotube tips have demonstrated the potential of these tools to achieve high-resolution images of single molecules. In addition, proof-of-principle demonstrations of nanotube functionalization and attachment of single molecules to these probes have been successfully made. Improved techniques for the growth and attachment of single wall carbon nanotubes as robust and well-characterized tools for AFM imaging are being developed. This work serves as a foundation toward development of single-molecule sensors and manipulators on nanotube AFM tips for a hybrid atomic force microscope that also has single-molecule fluorescence imaging capability. An individual single wall carbon nanotube (SWNT) attached to an AFM tip can function as a structural scaffold for nanoscale device fabrication on a scanning probe. Such a probe can have a novel role, to trigger specific biochemical reactions or conformational changes in a biological system with nanometer precision. The consequences of these perturbations can be read out in real time by single-molecule fluorescence and/or AFM sensing. Of particular interest is the possibility of electrical wiring of single redox enzymes to carbon nanotube scanning probes, which will allow for observation and electrochemical control of single enzymatic reactions, by monitoring fluorescence from a redox-active cofactor or the formation of fluorescent products. Enzymes """"""""nanowired"""""""" to carbon nanotube tips may enable extremely sensitive probing of biological stimulus-response with high spatial resolution, including product-induced signal transduction. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21GM071702-01
Application #
6794894
Study Section
Special Emphasis Panel (ZRG1-BPC-A (50))
Program Officer
Lewis, Catherine D
Project Start
2004-09-06
Project End
2007-08-31
Budget Start
2004-09-06
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$185,779
Indirect Cost
Name
California Institute of Technology
Department
Chemistry
Type
Schools of Engineering
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Kong, Qingjun; Vazquez, Maribel (2009) Flow-induced shear stresses increase the number of cell-cell contacts within extracellular matrix. J Biomed Mater Res A 89:968-79