Wednesday, February 13, 2008

Wiring Up DNA

Measuring the conductivity of DNA could provide a way to detect mutations.

By Helen Pearson

Hot-wired: By placing a double-stranded DNA segment in a gap in a single-walled carbon nanotube, researchers have measured the electrical properties of the biological molecule. Since even a single mismatch in the DNA letters affects the conductivity of the segment, the system could eventually be the basis of chemical sensors to detect mutations in DNA. Credit: Colin Nuckolls

By wiring up DNA between two carbon nanotubes, researchers have measured the molecule's ability to conduct electricity. Introducing just a single letter change can drastically alter the DNA's resistance, the researchers found, a phenomenon that they plan to exploit with a device that can rapidly screen DNA for disease-linked mutations.

Measuring the electrical properties of DNA has proved tricky because the molecule and its attachments to electrodes tend to be very fragile. But in the new study, Colin Nuckolls, a professor of chemistry at Columbia University, in New York, teamed up with Jacqueline Barton, a professor of chemistry at Caltech, in Pasadena, CA, who's an expert in DNA charge transport. Nuckolls's group had previously developed a method for securely hooking up biological molecules to single-walled carbon nanotubes, which act as the electrodes in a miniscule circuit.

The researchers used an etching process to slice a gap in a carbon nanotube; they created a carboxylic acid group on the nanotube at each end of the gap. They then reacted these groups with DNA strands whose ends had been tagged with amine groups, creating tough chemical amide links that bond together the nanotubes and DNA. The amide linkages are robust enough to withstand enormous electrical fields.

The team estimated that DNA strands of around 15 base pairs (around 6 nanometers) in length had a resistance roughly equivalent to that of a similar-sized piece of graphite. This is a finding that the researchers might have expected since the chemical base pairs that constitute DNA create a stack of aromatic rings similar to those in graphite.

"In my opinion, the results of this work will survive, in contrast to many other publications on this topic," says chemist Bernd Giese, of the University of Basel, Switzerland. Previous estimates of DNA's conductivity have varied dramatically, Giese says, partly because it was unclear if the delicate DNA or its connection to electrodes had become damaged by the high voltages used. "One thinks one has burned the DNA to charcoal," Giese says. "It's extremely complicated experimentally."

Barton and Nuckolls performed two tricks with their wired-up DNA. For their first, they introduced a restriction enzyme that bound and cut the DNA at a specific sequence. When severed, the current running through the DNA vanished. "It's a way of biochemically blowing a fuse," Nuckolls says. It also demonstratesthat the DNA keeps its native structure in the circuit; if it had not, the enzyme would not recognize and cut the molecule.