Cause of neurological interference by carbon nanotubes discovered
1 September 2009
Carbon nanotubes hold many exciting possibilities, some of them in
the realm of the human nervous system. Recent research has shown that
carbon nanotubes may help regrow nerve tissue or ferry drugs used to
repair damaged neurons associated with disorders such as epilepsy,
Parkinson’s disease and perhaps even paralysis.
Yet some studies have shown that carbon nanotubes appear to interfere
with a critical signaling transaction in neurons, throwing doubt on the
tubes’ value in treating neurological disorders. No one knew why the
tubes were causing a problem.
Now a team of Brown University researchers in the US has found that
it’s not the tubes that are to blame. Writing in the journal
Biomaterials, the scientists report 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.
Neural Nanoblocker Metal catalysts — nickel and
particularly yttrium —
used to create carbon nanotubes can block a key
pathway in neurons. Experiments show the metal particles tend
to plug cellular pores normally reserved for calcium ions.
Jakubek / Brown University.
“It’s a problem we can fix. We can purify the nanotubes by removing
the metals,” said Lorin Jakubek, a Ph.D. candidate in biomedical
engineering and lead author of the paper.
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,” said 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, said Robert Hurt, professor of
engineering and a corresponding author on the paper.
Jakubek said she was surprised that the metals turned out to be the
cause. “Based on the literature, I thought it would be the nanotubes
themselves,” she said.
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