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Nanobiotechnology: tethering enzymes to make energy and diagnose disease

A major new area of study in nanobiotechnology is being supported by an NIH Pioneer Award. These studies derived from our earlier work investigating the compartmentalization of metabolic pathways in sperm. We and others discovered that the enzymes of glycolysis are tethered along a cytoskeletal element in the principal piece of the sperm flagellum. This “solid state design” gives the sperm the ability to produce energy locally down the length of the tail—a critical adaptation in cells that have a highly restricted localization of mitochondria. We are employing a biomimetic strategy (copying a design from nature) to target these enzymes on hybrid organic-inorganic devices where they would function to produce energy in the form of ATP. Getting enzymes to function efficiently while tethered to a support is a fundamental problem in nanobiotechnology. Our binding strategy immobilizes the enzymes in a specific orientation, as opposed to simple adsorption or covalent binding methods such as carboxyl-amine binding. We’ve found consistently that our enzymes function more efficiently when bound using this biomimetic approach, both individually and when looking at the efficiency of coupled reactions of tethered enzymes. We are now exploring the impacts of different substrates on tethered enzyme activity, such as the size and composition of various nanoparticles.

If we can successfully recreate the whole glycolytic pathway, it would enable the development of self-powered, implantable nanoscale medical devices, which could use circulating glucose as fuel. Such devices could carry out a variety of medical functions, such as delivering drugs to specific sites such as solid tumors at defined kinetic rates over time.

Now that we have many enzymes working while tethered, we are exploring other uses for them, such as point-of-care diagnostics to detect disease biomarkers. The use of these tethered enzymes has many advantages in speed, cost, and sensitivity in comparison to antibody-based biomarker detection. These attributes give us an opportunity to pursue point-of-care diagnostics for time-sensitive pathologies such as stroke, and applications such as traumatic brain injury where a quantifiable assessment is needed because the extent of injury is often not obvious.