A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field,
providing a research tool for studying neural responses

Date:
July 20, 2020
Source:
Massachusetts Institute of Technology
Summary:
Magnetic nanodiscs can be activated by an external magnetic field,
providing a research tool for studying neural responses.



FULL STORY ==========================================================================
In addition to responding to electrical and chemical stimuli, many of
the body's neural cells can also respond to mechanical effects, such as pressure or vibration. But these responses have been more difficult for researchers to study, because there has been no easily controllable method
for inducing such mechanical stimulation of the cells. Now, researchers
at MIT and elsewhere have found a new method for doing just that.


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The finding might offer a step toward new kinds of therapeutic treatments, similar to electrically based neurostimulation that has been used to
treat Parkinson's disease and other conditions. Unlike those systems,
which require an external wire connection, the new system would be
completely contact-free after an initial injection of particles, and
could be reactivated at will through an externally applied magnetic field.

The finding is reported in the journal ACS Nano, in a paper by former MIT postdoc Danijela Gregurec, Alexander Senko PhD '19, Associate Professor
Polina Anikeeva, and nine others at MIT, at Boston's Brigham and Women's Hospital, and in Spain.

The new method opens a new pathway for the stimulation of nerve cells
within the body, which has so far almost entirely relied on either
chemical pathways, through the use of pharmaceuticals, or on electrical pathways, which require invasive wires to deliver voltage into the
body. This mechanical stimulation, which activates entirely different
signaling pathways within the neurons themselves, could provide a
significant area of study, the researchers say.

"An interesting thing about the nervous system is that neurons can
actually detect forces," Senko says. "That's how your sense of touch
works, and also your sense of hearing and balance." The team targeted a particular group of neurons within a structure known as the dorsal root ganglion, which forms an interface between the central and peripheral
nervous systems, because these cells are particularly sensitive to
mechanical forces.

The applications of the technique could be similar to those being
developed in the field of bioelectronic medicines, Senko says, but those require electrodes that are typically much bigger and stiffer than
the neurons being stimulated, limiting their precision and sometimes
damaging cells.



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The key to the new process was developing minuscule discs with an
unusual magnetic property, which can cause them to start fluttering
when subjected to a certain kind of varying magnetic field. Though the particles themselves are only 100 or so nanometers across, roughly a
hundredth of the size of the neurons they are trying to stimulate, they
can be made and injected in great quantities, so that collectively their
effect is strong enough to activate the cell's pressure receptors. "We
made nanoparticles that actually produce forces that cells can detect
and respond to," Senko says.

Anikeeva says that conventional magnetic nanoparticles would have
required impractically large magnetic fields to be activated, so finding materials that could provide sufficient force with just moderate magnetic activation was "a very hard problem." The solution proved to be a new
kind of magnetic nanodiscs.

These discs, which are hundreds of nanometers in diameter, contain a
vortex configuration of atomic spins when there are no external magnetic
fields applied. This makes the particles behave as if they were not
magnetic at all, making them exceptionally stable in solutions. When
these discs are subjected to a very weak varying magnetic field of a few millitesla, with a low frequency of just several hertz, they switch to a
state where the internal spins are all aligned in the disc plane. This
allows these nanodiscs to act as levers - - wiggling up and down with
the direction of the field.

Anikeeva, who is an associate professor in the departments of Materials
Science and Engineering and Brain and Cognitive Sciences, says this
work combines several disciplines, including new chemistry that led to development of these nanodiscs, along with electromagnetic effects and
work on the biology of neurostimulation.

The team first considered using particles of a magnetic metal alloy that
could provide the necessary forces, but these were not biocompatible
materials, and they were prohibitively expensive. The researchers found
a way to use particles made from hematite, a benign iron oxide, which
can form the required disc shapes. The hematite was then converted into magnetite, which has the magnetic properties they needed and is known
to be benign in the body. This chemical transformation from hematite to magnetite dramatically turns a blood-red tube of particles to jet black.

"We had to confirm that these particles indeed supported this really
unusual spin state, this vortex," Gregurec says. They first tried out
the newly developed nanoparticles and proved, using holographic imaging
systems provided by colleagues in Spain, that the particles really did
react as expected, providing the necessary forces to elicit responses from neurons. The results came in late December and "everyone thought that was
a Christmas present," Anikeeva recalls, "when we got our first holograms,
and we could really see that what we have theoretically predicted and chemically suspected actually was physically true." The work is still
in its infancy, she says. "This is a very first demonstration that it is possible to use these particles to transduce large forces to membranes
of neurons in order to stimulate them." She adds "that opens an entire
field of possibilities. ... This means that anywhere in the nervous system where cells are sensitive to mechanical forces, and that's essentially
any organ, we can now modulate the function of that organ." That brings
science a step closer, she says, to the goal of bioelectronic medicine
that can provide stimulation at the level of individual organs or parts
of the body, without the need for drugs or electrodes.


========================================================================== Story Source: Materials provided by
Massachusetts_Institute_of_Technology. Original written by David
L. Chandler. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Danijela Gregurec, Alexander W. Senko, Andrey Chuvilin, Pooja
D. Reddy,
Ashwin Sankararaman, Dekel Rosenfeld, Po-Han Chiang, Francisco
Garcia, Ian Tafel, Georgios Varnavides, Eugenia Ciocan, Polina
Anikeeva. Magnetic Vortex Nanodiscs Enable Remote Magnetomechanical
Neural Stimulation. ACS Nano, 2020; DOI: 10.1021/acsnano.0c00562 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200720152406.htm

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