DNA in nanotubes sorts molecules

By Kimberly Patch, Technology Research News

Cells are especially selective gatekeepers, allowing the right chemicals through the cell membrane at the right time. The ability to allow some molecules through the membrane while blocking others is useful in biotechnology and nanotechnology applications that require that specific molecules be selected or sorted.

Researchers from the University of Florida have made a synthetic membrane that recognizes certain biochemical molecules and allows them to pass through.

The method could be used to make biological sensors like those needed for genetics research, and to sort biological molecules, said Charles Martin, a professor of chemistry at the University of Florida.

The synthetic membrane is made up of tiny gates and molecular gatekeepers. The gates are gold nanotubes and DNA strands attached to the nanotubes determine which molecules pass through, said Martin.

To form a working membrane, the researchers had to match the size of the gate to the size of the gatekeeper. "A gate-keeping man can block a gate the size of a window, but this man could not block a gate the size of a garage door," said Martin. "So we need to make nanotubes with diameters comparable to the size of the DNA molecules -- in the 10 nanometer range." A nanometer is one millionth of a millimeter, or the span of 10 hydrogen atoms.

The researchers used template synthesis to make nanotubes of the correct size. They electrically deposited gold atoms inside the 30-nanometer diameter pores of a polycarbonate template membrane to make gold nanotubes with inner diameters ranging from 8 to 12 nanometers.

The researchers also had to determine what kind of DNA strands would be the best gatekeepers. They used DNA hairpin molecules to select target DNA strands and allow them to pass through the nanotubes.

The DNA gatekeeper molecule is made from the same building blocks as biological DNA -- the bases adenine, cytosine, guanine and thymine attached to a sugar-phosphate backbone. Single-stranded DNA can combine with other strands that contain complementary bases -- adenine across from thymine, and cytosine across from guanine.

Hairpin DNA molecules contain complementary bases on a single strand, and when these bases join, the single-strand forms a hairpin-like shape. The researchers' hairpins strands contain a loop before the joined portion.

The researchers affixed hairpin DNA to the insides of the gold nanotubes in the membrane so that the loops floated freely. DNA present in the environment that contained a stretch of bases complementary to the exposed loops combined with the gatekeeper DNA, then passed through when other complementary strands displaced them.

The flow of DNA molecules that contain exactly matching segments is increased because when there is an excess of matching segments, the segments connected to the loops quickly disconnect, according to Martin. This rapid displacement of connected segments accelerates the transport of matching segments through the membrane.

The researchers found that the nanotube membrane transported five times as many DNA segments that contained exactly complementary sequences to the DNA hairpin loop as segments that contain the complementary sequence with a single base mismatch

The researchers are working on making the membranes more selective and quicker, said Martin. The method also needs to be tested with more realistic samples, like DNA extracted from cells.

The method could be ready for practical use in in five to ten years, said Martin.

Ultimately, the research is aimed at tapping the vast experience of nature, according to Martin."Living systems use bio and nano devices routinely -- ion channels, ribosomes, protein complexes, molecular motors et cetera," he said. "I'm trying to make bio and nano devices that mimic the functions of the natural ones."

Martin's research colleagues were Punit Kohli, C. Chad Harrell, Zehui Cao, Rahela Gasparac, and Weihong Tan. The work appeared in the August 13, 2004 issue of Science. The research was funded by the National Science Foundation (NSF).

Timeline:   5-10 years
Funding:   Government
TRN Categories:  Biotechnology; Nanotechnology
Story Type:   News
Related Elements:  Technical paper, "DNA-Functionalized Nanotube Membranes with Single-Base Mismatch Selectivity," Science, August 13, 2004


November 3/10, 2004

Page One

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DNA in nanotubes sorts molecules

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Nanotubes lengthen to centimeters
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