Synthetic Membrane Channels Constructed with DNA-Based Nanostructures

Scientists have shown for the first time that synthetic, lipid-membrane channels can be constructed by using a technique employing DNA molecules as building materials for custom-designed, self-assembling, nanometer-scale structures. The results suggest potential applications as molecular sensors, antimicrobial agents, and drivers of novel nanodevices.

Physicists at the Technical University of Munich (TUM; Garching, Germany) and the University of Michigan (Ann Arbor, MI, USA) have applied the emerging field of DNA-nanotechnology, including “scaffolded DNA origami,” to mimic the shape and function of one of the most widespread and important natural nanomachines – the biological transmembrane channel. The synthetic structure consists of a needle-like stem (42 nm long, 2 nm internal diameter) that penetrates and spans a lipid bilayer membrane. The stem is partly sheathed by a barrel-shaped cap that adheres to the membrane, in part via a ring of 26 cholesterol moieties around the edge of the cap that helps the device dock while the stem forms a channel. The device is formed by 54 double-helical DNA domains on a honeycomb lattice. Evidence is presented suggesting that these nanostructures function much like cellular ion channels. For example, in single-channel electrophysiological measurements there were similarities to natural ion channels, such as conductance on the order of 1 nanosiemens and channel gating.

"We have not tested this yet with living cells, but experiments with lipid vesicles show that our synthetic device will bind to a bilayer lipid membrane in the right orientation, [...] forming a pore," explains Prof. Friedrich Simmel, co-coordinator of the Excellence Cluster Nanosystems Initiative Munich. Further experiments demonstrated that the resulting pores have electrical conductivity that suggests they could act like the voltage-controlled gates present in cells and that the transmembrane current could be tuned by adjusting fine structural details.

This study of the first artificial channel suggests a number of potential applications. "If you want, for example, to inject something into a cell, you have to find a way to punch a hole into the cell membrane, and this device can do that, at least with model cell membranes," says Prof. Hendrik Dietz, a fellow of the TUM Institute for Advanced Study. To test one potential application, the researchers used these devices as "nanopores" for several different molecular sensing experiments and confirmed that it is possible, by measuring changes in electrical characteristics, to record the passage of single molecules. Because this approach allows both geometric and chemical tailoring of the membrane channels, it might offer advantages over two other families of molecular sensors, based on biological and solid-state nanopores respectively.

Other conceivable applications remain to be investigated. One notion is to imitate viruses or phages to kill targeted bacteria. Synthetic channels might be used as nanoneedles to inject material into cells for medical use such as gene-therapy or for basic studies of cell metabolism. Another idea is to harness the ion flux to drive sophisticated nanodevices.

The study was reported November 16, 2012, in the journal Science.

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Technische Universitaet Muenchen
University of Michigan