Issue Date: November 19, 2012
Membrane Pore Made From DNA
The first synthetic ion channel made from DNA that can spontaneously assemble within a lipid membrane has been designed and built by researchers in Munich, Germany (Science, DOI: 10.1126/science.1225624).
Modeled after α-hemolysin, a bacterial protein ion channel that acts as an antibiotic, the new DNA-based pore may one day find application as an antimicrobial agent. Other potential applications range from drug delivery to sensor technology, notes Kurt Vesterager Gothelf of the Centre for DNA Nanotechnology at Denmark’s Aarhus University, who was not involved in the research.
Critics of DNA nanotechnology often claim that “interesting and aesthetically beautiful DNA nanostructures have been created with DNA origami but that the actual usefulness of DNA nanostructures is questionable,” Gothelf says. The German team’s work shows that DNA origami—designed folding of DNA into defined shapes—is evolving to also produce functional structures, he says.
The pore self-assembles from a long DNA strand whose nucleotide bases were designed using computer programs to hybridize into a three-dimensional structure that has two main components: a lipid-membrane-traversing channel and a barrel-shaped cap, says Friedrich C. Simmel, a physicist at Technical University Munich, who led the research with his TUM collaborator Hendrik Dietz.
The channel’s architecture is reinforced by 156 smaller strands of DNA that hybridize to buttress the main structure. Some of these reinforcing oligonucleotides are linked to molecules of cholesterol. This enables the channel, which is polar because of its DNA makeup, to slip into the nonpolar membrane.
The team used electrophysiology to show that the new channel allows transport of ions and DNA hairpins through its pore in much the same way a traditional protein channel would. The channel also has “impressive stability, commensurate with that of biological ion channels,” notes Michael S. Strano, who develops carbon nanotube pores at Massachusetts Institute of Technology, in an associated Science commentary (DOI: 10.1126/science.1231024).
However, the DNA channel still has much room for improvement, Simmel says. The researchers would like to eliminate ion leakage across the membrane that occurs outside the pore’s interior ion channel, he says. And they would also like to reduce the channel’s size, which is currently several times larger than that of α-hemolysin, and improve its ability to slip into membranes made from any kind of lipid. Currently, the system works only with certain lipids.
Making these improvements is a matter of developing better computer-based designs for the DNA channel, the researchers say. An advantage of a DNA-based pore design over protein sequence design is that DNA 3-D structures more often self-assemble as planned, Simmel says.
“The possibilities with this [DNA] system are endless,” Strano notes, “because one can vary the sequence and corresponding structure quite easily, analogous to site-directed mutagenesis in biology.”
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