Blame the metal, not the nanotubes

BROWN (US)—Carbon nanotubes offer promising new treatment options for neurological disorders such as epilepsy, Parkinson’s disease, and perhaps even paralysis. The problem is they appear to interfere with critical signals in neurons. A new study, however, says don’t blame the tubes.

A team of Brown University researchers report in the journal Biomaterials that the metal catalysts used to form the tubes are the culprits, and that minute amounts of one metal—yttrium—could impede neuronal activity.

The findings mean that carbon nanotubes without metal catalysts may be able to treat human neurological disorders, although other possible biological effects still need to be studied. Recent research has shown that carbon nanotubes may help regrow nerve tissue or ferry drugs used to repair damaged neurons.

“We can purify the nanotubes by removing the metals,” says Lorin Jakubek, a Ph.D. candidate in biomedical engineering and lead author of the paper, “so, it’s a problem we can fix.”

Jakubek took single-walled carbon nanotubes to the laboratory of Diane Lipscombe, a Brown neuroscientist. The researchers zeroed in on ion channels located at the end of neurons’ axons. These channels are gateways of sorts, driven by changes in the voltage across neurons’ membranes.

When an electrical signal, known as an action potential, is triggered in neurons, these ion channels “open,” each designed to take in a certain ion. One such ion channel passes only calcium, a protein that is critical for transmitter release and thus for neurons to communicate with each other.

In experiments using cloned calcium ion channels in embryonic kidney cells, the scientists discovered that nickel and yttrium, two metal catalysts used to form the single-walled carbon nanotubes, were interfering with the ion channel’s ability to absorb the calcium.

Because its ionic radius is nearly identical to calcium’s, yttrium in particular “gets stuck and prevents calcium from entering and passing through. It’s an ion pore blocker,” says Lipscombe, who specializes in neuronal ion channels and is a corresponding author on the paper.

The experiments showed that yttrium in trace amounts—less than 1 microgram per milliliter of water—may disrupt normal calcium signaling in neurons and other electrically active cells, an amount far lower than what had been thought to be safe levels. With nickel, the amount needed to impede calcium signaling was 300 times higher.

“Yttrium is so potent that . . . a very low nanotube dose” would be needed to affect neuronal activity, says Robert Hurt, professor of engineering and a corresponding author on the paper.

Jakubek says she was surprised that the metals turned out to be the cause. “Based on the literature, I thought it would be the nanotubes themselves.”

The National Institutes of Health, the National Science Foundation, and the U.S. Environmental Protection Agency funded the research.

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