DNA Origami

This week I'd like to share with you an interesting recent paper published in the journal Science. The topic of the paper is DNA origami, which as the name suggests is literally doing origami with molecules of DNA. Since DNA forms basepairs in a predictable way, by cleverly designing the sequences of several strands of DNA you can coax them to self-assemble into a particular shape. So instead of following a list of paper folding maneuvers, the DNA acts based on its intrinsic chemistry. You can see the shapes formed by DNA origami under a microscope in amazing detail. Although the resolution isn't high enough to see individual atom or the double helix, you can still get a great impression of the overall shape assumed by the strands of DNA. I have provided some striking images depicting examples of DNA origami below. Pay particular attention to the bottom two rows, which are atomic force micrographs (method explained later).

Since we know a lot about the structure of DNA and how it behaves, developing DNA origami is limited largely by our creativity and insightfulness and less by any limits of fundamental scientific understanding. This is a great example of how scientific research builds on itself and how findings with no immediately apparent applications can come in useful down the road. Watson and Crick are credited with discovering the double helical structure of DNA. Consequently, the fact that DNA is double-stranded is practically orthodoxy! However it's not entirely true. DNA can exist in a less stable, single-stranded form as well. We distinguish these two forms by labeling them dsDNA and ssDNA, for double- or single-stranded. A strand of ssDNA readily basepairs with any other strand of ssDNA bearing a complementary sequence. Two strands needn't be 100% complementary; parts of one strand can pair with parts of the same strand, with a different strand, or with two or even more different strands.

Besides looking very cool under a microscope, there are a wide range of potential uses for this DNA origami. Until recently, DNA origami has been constrained to two dimensional shapes like smiley faces, stars, and other things (left). These are entertaining, but this technology has potential applications besides aesthetic. Maybe one day we can build containers for drugs using DNA origami that carry medicine to particular cells, say chemotherapy drugs to cancer cells while sparing healthy cells from the same fate. Maybe (and I believe this has been explored already) we can take advantage of the stability of DNA by using it to build scaffolds on which tissues or whole organs can grow. These two applications clearly require taking DNA origami into three dimensions, which is just what Dongran Han and his colleagues did.

In their designs they used one long piece of ssDNA, called the scaffold, and many small pieces of ssDNA, called staples. By choosing staples carefully, they were able to contort the scaffold into a desired shape. They began by building simple concentric circles in two dimensions with the scaffold weaving in and out between the rings. They then varied the parameters of their design to build three dimensional shapes with circular cross sections. They managed to build hemispheres, spheres, ellipsoids (stretched spheres), and flasks. They called their DNA flask the "nanoflask" in reference to its nanoscale size. The pictures of these shapes shown below are transmission electron micrographs in black and white and atomic force micrographs in yellow and red. Electron microscopes use a beam of electrons instead of light to focus on objects much smaller than the wavelength of visible light. Atomic force microscopes feel their way through a sample using a tiny needle tipped with a single atom.

There are several things about this project that I find particularly interesting. First, it combines knowledge from diverse fields, most obviously biology and chemistry for the DNA and physics for the instrumentation. Second, it makes some quite stunning images, glimpses into the
nanoscale lying beyond ordinary human comprehension. And last I think there's something to be said for using our understanding of basic biology to build things. Until relatively recently, biology has largely eluded engineering (unless you count examples such as selective breeding, which in my book is too indirect to qualify). At the time of the physicist Richard Feynman's death in 1988, his blackboard contained, among other things, the statement "What I cannot create, I do not understand." While clearly an engineering discipline, I think that synthetic biology equally plays a role in refining our understanding of biology at a basic level.

Image Credit: In order of appearance: Abauseind (via Wikimedia); Adapted from Rothemund (Figure 2); Adapted from Han et al. (Figure 3)

References and Further Reading:

DNA Origami Gets Curves. KatiePhD.

Han, D. et al. DNA Origami with Complex Curvatures in Three-Dimensional Space. Science 332, 342–346 (2011).

Rothemund, P. Folding DNA to Create Nanoscale Shapes and Patterns. Nature 440, 297–302 (2006).