Nanobiotechnology offers the possibility of new forms of medical treatments, such as implantable devices that carry out biological or mechanical functions, or deliver drugs to specific tissues. Because proteins function so efficiently at this small scale, they will likely be major components of nanodevices. However, a number of important obstacles must be overcome for nanodevices to realize their potential. One of the most critical problems is how to supply implantable nanodevices with energy. Our work on the physiology of mammalian sperm has inspired us with a strategy to address this important issue. Sperm generate ATP throughout the flagellar principal piece by using glycolytic enzymes tethered to a cytoskeletal support by means of germ cellspecific targeting domains. We hypothesize that by identifying and modifying these domains, we can generate recombinant glycolytic enzymes that can be bound to a support and retain function. As proof of principle, we have made modified forms of the first two enzymes in this pathway, and show their activities in series when coupled to the same support. To our knowledge, this is the first demonstration of sequential enzymatic activities in a multi-step pathway on a hybrid organic-inorganic device. These data also support our hypothesis that sperm provide a natural model of how to produce ATP locally on nanodevices. We propose to construct similarly modified recombinant forms of the rest of the enzymes of glycolysis, as well as an additional enzyme that will be needed for co-enzyme regeneration. We shall then test the activities of these enzymes individually, in sub-assemblies, and in series on single supports in our effort to design a system through which implantable nanodevices can produce their own energy from freely available circulating glucose. If successful, our innovative strategy will produce an enabling technology that should advance a variety of medical applications for nanobiotechnology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
8DP1EB016541-04
Application #
8306909
Study Section
Special Emphasis Panel (ZGM1-NDPA-B (02))
Program Officer
Liu, Christina
Project Start
2009-09-30
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$762,300
Indirect Cost
$267,300
Name
Cornell University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Cohen, Roy; Buttke, Danielle E; Asano, Atsushi et al. (2014) Lipid modulation of calcium flux through CaV2.3 regulates acrosome exocytosis and fertilization. Dev Cell 28:310-21
Gao, Lizeng; Giglio, Krista M; Nelson, Jacquelyn L et al. (2014) Ferromagnetic nanoparticles with peroxidase-like activity enhance the cleavage of biological macromolecules for biofilm elimination. Nanoscale 6:2588-93
Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus et al. (2013) Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS. PLoS One 8:e61434