How to make a molecular nanobot

May 13, 2010

Scientists have programmed an autonomous molecular nanorobot made out of DNA to start, move, turn, and stop while following a DNA track.

(Paul Michelotti)

The development could ultimately lead to molecular systems that could be used for medical therapeutic devices and molecular-scale reconfigurable robots—robots made of many simple units that can reposition or even rebuild themselves to accomplish different tasks.

Molecular robots, in theory, could be programmed to sense their environment (say, the presence of disease markers on a cell), make a decision (that the cell is cancerous and needs to be neutralized), and act on that decision (deliver a cargo of cancer-killing drugs). Or they could be programmed to assemble complex molecular products.

“In normal robotics, the robot itself contains the knowledge about the commands, but with individual molecules, you can’t store that amount of information, so the idea instead is to store information on the commands on the outside,” says Nils G. Walter, professor of chemistry and director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan in Ann Arbor. And you do that by “imbuing the molecule’s environment with informational cues,” says Milan N. Stojanovic, a faculty member in the Division of Experimental Therapeutics at Columbia University.

“We were able to create such a programmed or ‘prescribed’ environment using DNA origami,” explains Hao Yan, professor of chemistry and biochemistry at Arizona State University. DNA origami is a type of self-assembled structure made from DNA that can be programmed to form nearly limitless shapes and patterns. Exploiting the sequence-recognition properties of DNA base pairing, DNA origami are created from a long single strand of DNA and a mixture of different short synthetic DNA strands that bind to and “staple” the long DNA into the desired shape. The origami used in the Nature study was a rectangle that was 2 nanometers (nm) thick and roughly 100 nm on each side.

The researchers constructed a trail of molecular “bread crumbs” on the DNA origami track by stringing additional single-stranded DNA molecules, or oligonucleotides, off the ends of the staples. These represent the cues that tell the molecular robots what to do—start, walk, turn left, turn right, or stop, for example—akin to the commands given to traditional robots.

To build the 4-nm-diameter molecular robot, the researchers started with a common protein called streptavidin, which has four symmetrically placed binding pockets for a chemical moiety called biotin. Each robot leg is a short biotin-labeled strand of DNA, “so this way we can bind up to four legs to the body of our robot,” Walter says. “It’s a four-legged spider,” quips Stojanovic. Three of the legs are made of enzymatic DNA, which is DNA that binds to and cuts a particular sequence of DNA. The spider also is outfitted with a “start strand”—the fourth leg—that tethers the spider to the start site (one particular oligonucleotide on the DNA origami track). “After the robot is released from its start site by a trigger strand, it follows the track by binding to and then cutting the DNA strands extending off of the staple strands on the molecular track,” Stojanovic explains.

“Once it cleaves,” adds Yan, “the product will dissociate, and the leg will start searching for the next substrate.” In this way, the spider is guided down the path laid out by the researchers. Finally, explains Yan, “the robot stops when it encounters a patch of DNA that it can bind to but that it cannot cut,” which acts as a sort of flypaper.

Using atomic force microscopy and single-molecule fluorescence microscopy, the researchers were able to watch spiders crawling over the origami, showing that they were able to guide their molecular robots to follow four different paths.

More info: Caltech news and Molecular robots guided by prescriptive landscapes