Picture of the Week: DNA Bunny

Aug 27, 2015

The candy-colored bunny above looks good enough to eat, but it’s no Easter leftover. This is a 3-D-printed model of a microscopic, rabbit-shaped structure made entirely out of DNA. An enlarged picture of that tiny structure (which is 50 nanometers long) appears at left. Can you make out its cottontail shape? 

For just over 30 years, scientists have been experimenting with DNA to build nanostructures, ranging from simple, 2-D sheets to more complex shapes such as octahedrons, stars, and even smiley faces.

“The amazing thing is that DNA can both function as an information storage molecule, but it can also function as kind of like a Lego building block,” says Shawn Douglas, who works on DNA nanotechnology at his lab at the University of California, San Francisco (he wasn’t involved in the bunny work).

Indeed, many of the traits that make DNA useful in nature are befitting nanoscale construction material. For instance, strands of DNA will self-assemble in solution, thanks to complementary base pairing. Plus, the nucleic acid can bind to other molecules, such as proteins, “allowing it to serve as a scaffold for complex nanomachinery,” according to a 2010 article appearing in Nature. In other words, scientists can stick stuff on DNA that tailors it to certain tasks.

The team that created the rabbit used a DNA-manipulating technique called DNA origami, which was first described in 2006. In a nutshell, the method involves folding a long piece of single-stranded DNA into a predesigned shape with the help of shorter strands—called “staples”—which bind to complementary sequences on the longer strand, effectively “stapling” it in place.

But the researchers added a twist to that approach, borrowing ideas from both computer graphics and graph theory.

Reporting in a recent edition of Nature, they used 3-D software to first create shapes known in CG parlance as “meshes.” (Basically, a mesh is a series of polygons stuck together to form a figure that conveys three-dimensionality. Picture a Swarovski crystal figurine, and that’s kind of how the bunny mesh looks. See the picture below.)

Next, they used an algorithm to figure out how a single strand of DNA could be routed along every edge of the mesh. To develop the algorithm, they drew on a mathematical concept known as a Eulerian circuit, which is a circuit that touches each edge on a multi-sided shape only once. 

If, in scouting a given mesh, the algorithm couldn’t find a route that hadn’t been crossed, it figured out which edges to double back on that would result in a minimal amount of overlapping. Once an entire route was determined, the software populated it with the sequence of the chosen DNA strand. (They used DNA from a bacteriophage with a known sequence.)

The final steps entailed defining the “staple” DNA strands that would hold the long strand together in key areas; ordering those strands from a DNA synthesizing company; and throwing the long with the short together in solution to allow them to self-assemble.

What materialized were 3-D nanostructures that, when viewed under the microscope, in fact resembled the bunny mesh, as well as several other shapes that the researchers had designed, including a bottle and a waving stickman. (For the record, the bunny wasn’t chosen by whim: It’s based on an experimental model commonly used in testing computer graphics techniques, known as the “Stanford bunny,” for the university where researchers first developed it. The model itself is based on a terra cotta rabbit.)

The nanostructure shapes are “more inflated and open” than previous ones designed through DNA origami, says Björn Högberg, an associate research professor at the Karolinska Institutet in Stockholm, Sweden, who oversaw the work. “What people had been doing previously was to make 3-D structures that were a little bit more like solid bricks,” he says—that is, the DNA arrangement interlocked kind of like Lincoln Logs, whereas these newer structures are more like cages.

The type of DNA conformation a researcher decides to use in a nanostructure “depends on what type of application you want to use the origami structures for,” says Högberg.

While the bunny et al. are more proof-of-concept, the potential applications for DNA nanostructures in general are manifold. Högberg’s team, for instance, is investigating cellular communication by attaching proteins in different patterns on DNA origami scaffolds and exposing them to breast cancer cells. And it’s conceivable that some time in the future, a DNA nanostructure could ensconce a drug, and upon recognizing a target cell protein in the body, release it.

DNA is a kind of “superstar molecule,” says Douglas. There’s plenty more it can do, now that the bunny’s out of the hat.