Machines, motors, mechanization — what comes to mind when you hear these terms? Maybe something big and clunky; maybe something powerful and sleek. But my guess would be that your mind doesn’t jump to a technology miniscule enough for nanochemistry research, gentle enough to handle DNA, and precise enough to locate even a single mutation. Now, what if I told you that this incredible little machine was engineered out of DNA itself? Surprised? Just wait — it gets better.
Let’s back up to the fundamentals. Molecular machines, such as these DNA machines, are compounds made up of a series of molecules in a complex that produces specific responses to certain stimuli. In our case, the molecules making up the complex are strands of DNA. One common example of a DNA machine is a set of three DNA strands that acts as a pair of tweezers. Normally, the three sections (A, B, and C) of DNA bind to each other in a linear formation; chemists engineer the sequences of these strands so that A will bind to half of B and half of C, leaving the other two halves open. The open ends of B and C have been designed so that they are complementary to a “target” strand of DNA.
When this target strand is present, the DNA tweezers will hold onto it by forming new bonds with the complementary sequences of B and C. One possible application of DNA tweezers is the fundamental task of synthesizing a DNA sequence. By using tweezers that are closed by specific sequences of nucleotides, Bernard Yurke at Bell Laboratories says researchers can select and assemble specific patterns from a heap of random sequences. He likens it to “intelligent glue” and notes it has an advantage over other techniques because it’s highly selective.
DNA walkers are even more complex types of DNA machines that operate on similar principles to those of the DNA tweezer. In this case, though, our DNA machine can autonomously move along a sequence of RNA or DNA. During this “walk,” the machines can identify mutations, carry molecular cargo, and synthesize a DNA template. One core feature of this process is the addition of Ribonuclease H, which breaks the bonds between the walker and the target strand through hydrolysis, allowing the walker to move further down the line to its next location. The basic tasks accomplished by DNA walkers can be applied to everything from detecting biomarkers for cancer to delivering drugs at targeted locations in the cell.
The basic tasks accomplished by DNA walkers can be applied to everything from detecting biomarkers for cancer to delivering drugs at targeted locations in the cell.
One notable drawback of DNA walkers is the difficulty ensuring high levels of accuracy while maintaining a rapid speed. In the past, chemists designing DNA walkers would usually need to prioritize one or the other. Giving a walker more legs — more strands of DNA — could increase fidelity, but the walker would move much more slowly.
Now, a team of researchers at Emory University has discovered a new way to approach the problem. They call it a DNA roller. Instead of creating the DNA structure as an independent unit, the researches have coated a silica bead with single stranded DNA. This allows the DNA to roll across the target RNA, which is anchored on a gold plate. The DNA roller operates 1000 times faster than any DNA walkers and, depending on the number of beads, can be tailored to roll in a straight line or in a random, self-avoiding pattern. This approach opens up many new opportunities in nanotechnology and DNA science. With the speed and reliability of the DNA roller, chemists can begin to apply DNA machines in laboratory situations, without having to compromise on speed or on reliability. It looks like you can now have your machine and use it, too.
High-speed DNA-based rolling motors powered by RNase H. Kevin Yehl, Andrew Mugler, Skanda Vivek, Yang Liu, Yun Zhang, Mengzhen Fan, Eric R. Weeks, Khalid Salaita. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.259; 30 November 2015
Gunther, Matthew. “Speedy DNA Nanomachines are on a Roll.” Chemistry World. 09 December 2015. <http://www.rsc.org/chemistryworld/2015/12/dna-nano-machine-motor-fast-roller>
MacNeil, John S. “DNA Tweezers, Please.” Science News. American Association for the Advancement of Science. 11 August 2000. <http://news.sciencemag.org/technology/2000/08/dna-tweezers-please>
Richards, Sabrina. “DNA Machines Inch Forward: Researchers are using DNA to computer, power, and sense.” The Scientist. LabX Media Group. 5 March 2013. <http://www.the-scientist.com/?articles.view/articleNo/34606/title/DNA-Machines-Inch-Forward/>