DNA Origami Seeds Offer Bottom-Up Methods for Molecular Self Assembly

Process uses rules of nature to build tiny machines.

Ribbon-like DNA tile crystals can be self-assembled from DNA origami seeds.

Construction of complex man-made objects—a car, for example, or even a pizza—almost invariably entails what are known as "top-down" processes, in which the structure and order of the thing being built is imposed from the outside (say, by an automobile assembly line, or the hands of the pizza maker).

While top-down methods have been successful in manufacturing a range of goods on the grand scale, they can be enormously expensive when it comes to small, highly precise objects like silicon chips with smaller and smaller transistors, according to Erik Winfree of the California Institute of Technology (Caltech).

Winfree, a computer scientist and associate professor of bioengineering, is developing a "bottom-up" alternative in which the order is imposed from within the object being made, so that it "grows" according to some built-in design. The basis of the technology is an information-containing DNA "seed" that can direct the self-assembled bottom-up growth of DNA tiles in a precisely controlled fashion.

“We are finally beginning to understand how to program information into molecules and have that information direct algorithmic processes,” Winfree said. "It exhibits a degree of control over information-directed molecular self-assembly that is unprecedented in accuracy and complexity.”

While bottom-up approaches have been extremely useful in biology, they haven't played as significant a role in technology, "because we don't have a great grasp on how to design systems that build themselves,” Winfree said. “Most examples of bottom-up technologies are specific chemical processes that work great for a particular task, but don’t easily generalize for constructing more-complex structures."

To understand how complexity can be programmed into bottom-up molecular fabrication processes, Winfree and his colleagues study and understand the processes—or algorithms—that generate organization not just in computers but also in the natural world.
"Every cell, it appears, is a kind of universal computer that can be instructed in seemingly limitless ways by a DNA genome that specifies what chemical processes to execute, thus building an active organism," Winfree said.

Winfree's coworker at Caltech, Paul W. K. Rothemund, pioneered the seed-DNA technology that allows tiny "DNA origami" structures to self-assemble into nearly arbitrary shapes (such as a smiley face and a map of the Western Hemisphere). The researchers designed several different versions of a DNA origami rectangle, 95 by 75 nanometers, which served as the seeds for the growth of different types of ribbon-like DNA crystals. The seeds were combined in a test tube with other bits of DNA, called "tiles," heated, and then cooled slowly.

At the lower temperature, the tiles start to stick to each other and to the origami. In this way, the DNA ribbons self-assemble, but only into forms such as ribbons with particular widths and ribbons with stripe patterns prescribed by the original seed.

Information transfer from the bottom up a has long been exploited by natural evolution, Winfree said. In some ways, the process is similar to how the fertilized seeds of plants or animals contain information that directs the growth and development of those organisms.

"Tasks can be solved by carrying out well-defined rules,” he says, “and these rules can be carried out by a mindless mechanism such as a computer."

A research paper on the work appeared in a March issue of the Proceedings of the National Academy of Sciences.

The work was supported by grants from the National Aeronautics and Space Administration's astrobiology program, the National Science Foundation, and the Focus Center Research Program, and a gift from Microsoft Research.

—By Leslie Fink/NSF from materials provided by Caltech.