DNA Origami Takes
Engineering to a Nano


It all started with a smiley face.

In 2006 Paul Rothemund, a senior research associate at the California Institute of Technology, invented DNA origami by using specific pairings of bases in a strand of viral DNA and the bases in shorter DNA strands to create two-dimensional nanostructures (for example, a star and a smiley face) out of the material.

These specific interactions between complementary base pairs in the DNA structure allow engineers to bend the DNA strand into specific shapes—creating an innovative construction material with a broad range of design applications.

The process involves the folding of a long single strand of viral DNA using multiple smaller strands. These shorter strands bind the longer in various places, resulting in various shapes, along with many nanostructures. After DNA strands are synthesized, the scientists mix them together and the DNA particles assemble themselves into the desired shape.

The CanDo (computer-aided engineering for DNA origami) program can convert a 2-D DNA origami blueprint into a complex 3-D shape, seen here. Image: Do-Nyun Kim

A Rapidly Evolving Science

Advances in DNA origami are resulting in expanded applications, such as nanoswitches for electronics or drug-delivery devices that target cancer cells. Since Rothemund's initial discovery, scientists have developed a deeper understanding of the mechanical properties of DNA origami (for example, how to make curved and twisted 3-D shapes). For example, Mark Bathe, assistant professor of biological engineering at MIT, has created a software program called CanDo that allows scientists to predict the shape and structural properties (such as flexibility) of complex DNA origami.

"Predicting the 3-D solution shape and flexibility of scaffolded DNA origami structures is based on the assumption that the mechanical response of the DNA double-helix is well approximated by a homogeneous elastic rod with axial, twisting, and bending moduli that have been measured experimentally," says Bathe.

Double-strand crossovers are modeled as rigid links connecting neighboring helices that are initially positioned on either a honeycomb or square lattice, providing internal constraints that deform DNA from its straight, rod-like conformation to complex shapes.

"Computational prediction of deformed DNA shapes is performed using the finite element method," says Bathe. "The flexibility of deformed DNA origami shapes is computed using the equipartition theorem of statistical mechanics and normal mode analysis." Innovative research continues to show how this unique self-assembly method can create materials and structures with predesigned functions. Several research institutions, including Harvard University and the National Center for Nanoscience and Technology, have reported success in building self-assembling and self-destructing DNA origami devices that can penetrate diseased cells and release lethal drug payloads. DNA is also the framework for structures that arrange metal nanoparticles into specific geometries to behave like metallic nanowires.

"DNA origami have also been used to template little gold spirals that can selectively absorb one or the other of two polarizations of light," says Rothemund. "This means that when broad-spectrum, circularly polarized white light illuminates the DNA origami, right-handed spirals look red and left-handed spirals look blue. Basically DNA origami will allow us to make all kinds of optical nanostructures that will have pre-programmed responses to light."

Nanoelectronic Manufacturing

Artificial DNA nanostructures show great promise for organizing functional materials to create advanced nanoelectronic or nano-optical devices. DNA origami can display 6-nm-resolution patterns for binding sites, theoretically allowing them to arrange materials such as carbon nanotubes, silicon nanowires, or quantum dots into complex patterns.

One of the biggest challenges with this approach is that DNA origami are synthesized in solution and virtually impossible to align on a surface—depositing a drop of DNA origami solution on a substrate results in a totally random arrangement—"similar to throwing a deck of playing cards on the floor," says Rothemund.

This, of course, makes it very difficult to integrate the origami with conventionally fabricated microcircuitry, for example. However, Rothemund and research collaborators at IBM have demonstrated that DNA origami can be precisely aligned on a surface using the same kinds of technology used to make computer chips. Electron-beam lithography and dry oxidative etching create "sticky" spots on silica- or carbon-based substrates that precisely match the shapes of the DNA origami.

When the DNA origami solution is poured over the surface, the DNA origami (and any devices they carry) line up and arrange themselves exactly as desired on the pattern of sticky patches. "This makes them much easier to study or to wire up any devices they may carry," Rothemund says.

Mark Crawford is an independent writer.

Artificial DNA nanostructures show great promise for organizing functional materials to create advanced nanoelectronic or nano-optical devices.


December 2012

by Mark Crawford, ASME.org