TEMPE,
Ariz. – In the fifty-year history since the structure
of DNA was first revealed, what was once a Nobel
prize- winning research discovery has become an omnipresent
cultural icon co-opted for promoting everything from
fragrances to musical acts. Now, the familiar DNA
double helix is serving as a microscopic trellis
in order to further advances in nanotechnology aimed
at improving human health.
Hao Yan, a researcher at the Biodesign Institute
at Arizona State University and an assistant professor
in ASU's Department of Chemistry and Biochemistry,
recently created unique arrays of proteins tethered
onto self-assembled DNA nanostructures.
While other efforts in recent years have focused
on learning how to build DNA-based nanostructures,
Yan's work is novel because it makes it feasible
to attach any desired biomolecule onto DNA nanostructures.
Such work is an important step and can serve as a
future foundation for biocatalytic networks, drug
discovery or ultrasensitive detection systems.
"Rationally-designed DNA nanoscale architectural
motifs have for a long time been envisioned as scaffolds
for directing the assembly of biomolecules such as
proteins into a functional network," said Yan. "However,
the methods to control such assemblies are still
scarce. A robust and modular approach is needed. "
In his results, Yan and fellow institute researchers
Yan Liu, Chenxiang Lin, and Hanying Li have taken
advantage of the base pairing properties of DNA to
make the DNA nanostructures. By controlling the exact
position and location of the chemical bases within
a synthetic replica of DNA, Yan could potentially
fashion a variety of DNA assemblies.
In this case, Yan created a triple crossover DNA
tile, consisting of three side-by-side helices just
six nanometers in width and 17 nanometers in length.
One nanometer is one-billionth of a meter. By programming
into the assembly a short sequence of DNA that recognizes
a particular protein, called an aptamer, Yan created
a DNA molecule that could now function as a biomolecular
tether.
"This is the first time ever an aptamer has been
utilized to link proteins to self-assembled DNA nanoarrays," said
Yan.
Yan integrated an aptamer that recognizes the protein
thrombin, which is an important protein vital to
blood clotting. The technique allows for Yan to precisely
control both the position and spacing of the thrombin
proteins on the DNA nanoarray.
Yan's confirmed his results by using atomic force
microscopy, where the thrombin proteins bound to
the DNA nanoarray are seen as beads on a string.
Because of the ability of the protein binding to
be visualized, one intriguing application of the
technique may be in the application toward single
molecule proteomics studies.
"We are actively discussing applying this technology
to single molecule proteomics and to study protein-protein
interactions because the distance between interacting
proteins could be controlled with nanometer accuracy," said
Yan.
Also, by attaching different proteins onto the DNA
scaffold, Yan could directly visualize the binding
of a drug to its target molecule or recreate metabolic
pathways on a single array to mimic the way different
organelles function in a cell.
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