How to drop nanowires on cell targets

JOHNS HOPKINS (US)—Using virtual “tweezers,” researchers have dropped gold nanowires, each about one-two hundredth the size of a cell, on predetermined spots on target cells.

It’s the equivalent of dropping a toothpick on the head of a particular person in a stadium crowd of 100,000.

Once the nanowires are dropped in place using precise electrical fields, molecules coating the surfaces trigger a biochemical cascade of actions only in the cell where the wire touches, without affecting other cells nearby. Details are reported in Nature Nanotechnology.

The researchers say this technique could lead to better ways of studying cells. Eventually, it could be used to deliver medication exactly where it is needed, by, for instance, attacking abnormal cells while sparing their healthy neighbors.

“One of the biggest challenges in cell biology is the ability to manipulate the cell environment in as precise a way as possible,” said principal investigator Andre Levchenko, associate professor of biomedical engineering at Johns Hopkins University.

Precision becomes possible with the gold nanowires, metallic cylinders a few hundred nanometers or smaller in diameter.

Just as the unsuspecting stadium spectator would feel only a light touch from a toothpick dropped on the head, a cell reacts only to molecules released from the nanowire in one very precise place where the wire touches the cell’s surface.

The team developed nanowires coated with a molecule naturally released in the body by white blood cells. The molecule helps fight infection but also is capable of blocking tumor growth and halting viral replication. Exposure to too much of the TNF-alpha molecule, however, causes an organism to go into a potentially lethal septic shock, Levchenko says.

To test the system, the team cultured cervical cancer cells in a dish. They were able to plop the coated nanowires down in a precise location and trigger the desired cellular response in a very localized area

The TNF-alpha coating gives the nanowire a negative charge, making the wire easier to maneuver with the two perpendicular electrical fields of the “tweezer” device, a technique developed by doctoral researcher Donglei Fan.

“The electric tweezers were initially developed to assemble, transport and rotate nanowires in solution,” says Robert Cammarata, a professor of materials science and engineering. “Donglei then showed how to use the tweezers to produce patterned nanowire arrays as well as construct nanomotors and nano-oscillators. This new work with Dr. Levchenko’s group demonstrates just how extremely versatile a technique it is.”

The team members envision many possibilities for this method of subcellular molecule delivery.

“For example, there are many other ways to trigger the release of the molecule from the wires: photo release, chemical release, temperature release,” Levchenko says. “Furthermore, one could attach many molecules to the nanowires at the same time.” He adds that the nanowires can be made much smaller, but said that for this study the wires were made large enough to see with optical microscopy.

Levchenko sees the nanowires becoming a useful tool for basic research.

“With these wires, we are trying to mimic the way that cells talk to each other,” he says. “They could be a wonderful tool that could be used in fundamental or applied research.”

Drug delivery applications could be much further off, however, Levchenko notes. But, he says, “if the wires retain their negative charge, electrical fields could be used to manipulate and maneuver their position in the living tissue.”

The research was funded by the National Science Foundation and the National Institutes of Health.

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