A mechanical way of stimulating neurons


In addition to responding to electrical and chemical stimuli, many of the body’s nerve cells can also respond to mechanical effects such as pressure or vibration. But these reactions have been more difficult for researchers to study, as there is not an easily controllable way to generate such mechanical stimulation of cells. Now, researchers at MIT and elsewhere have discovered a new way to do this.

This discovery could lead to a move toward new types of therapeutic treatments, similar to electrolyte based neurostimulation that has been used to treat Parkinson’s disease and other conditions. Unlike systems that require an external wire connection, the new system will be completely contact-free after the initial injection of particles, and will be reactivated through an externally applied magnetic field.

The magazine has a search report ACS NanoFormer MIT postdoc Denzilla Gregrek, Alexander SNC PhD ’19, Associate Professor Polina Anikeva, and nine others at Boston Brigham and Women’s Hospital at MIT and a paper in Spain.

The new method opens up a new pathway for stimulation of nerve cells within the body, which until now has been almost entirely dependent on either the chemical pathway, through the use of pharmaceuticals, or on the electrical pathways that deliver voltage to the body. Requires aggressive wiring. . Researchers said that this mechanical stimulation, which activates a completely different signaling pathway within neurons, may provide an important area of ​​study.

“One interesting thing about the nervous system is that neurons can actually detect forces,” Senko says. “This is 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, as these cells are particularly sensitive to mechanical forces.

Applications of the technique may be similar to those developed in the field of bioelectronic medicine, Senko says, but require electrodes that are much larger and stiffer than neurons that are typically stimulated, their purity and sometimes Never limit harmful cells.

The key to the new process was developing minuscule disks with an unusual magnetic property, which can cause them to flake when subjected to a certain type of different magnetic field. Although the particles themselves are only 100 or so nanometers across, about one-hundredth of the size of the neurons they are trying to stimulate can be formed and injected in large quantities, so that they collectively The effects are strong enough to activate cell pressure receptors. “We produced nanoparticles that actually have forces that cells can detect and respond to,” says Senko.

Anykeva states that conventional magnetic nanoparticles are required to actively activate large magnetic fields, so finding materials that could provide sufficient force with just moderate magnetic activation was “a very difficult problem.” This solution proved to be a new type of magnetic nanodis.

These disks, which are hundreds of nanometers in diameter when not applied to any external magnetic field, have a vortex configuration of atomic spin. This makes the particles behave as if they were not magnetic, making them exceptionally stable in solutions. When these disks are subjected to a very weakly varying magnetic field of a few militasla, with a low frequency of several hertz, they switch to a position where the internal spines all align in the plane of the disc. This allows these nanodiscs to act as levers – swinging up and down along the direction of the field.

Anikeva, who is an Associate Professor in the departments of Materials Science and Engineering and Brain and Cognitive Sciences, says the work combines several disciplines, including new chemistry that has led to the development of these nanodisks as well as electrical Work on the biology of magnetic effects and neuroscience. .

The team first considered using particles of a magnetic metal alloy, which could provide the necessary forces, but these were not biochemical materials, and they were prohibitively expensive. Researchers found a way to use hematite, a particle made of benign iron oxide, that could create the required disc size. Hematite was then converted to magnetite, which has the magnetic properties they need and is known to be benign in the body. This dramatic chemical change from hematite to magnetite darkens a blood-red tube of particles.

“We had to confirm that these particles actually support this abnormal spin state, this vortex,” says Gregurek. He first tried out the newly developed nanoparticles and proved, using holographic imaging systems provided by colleagues in Spain, that the particles actually reacted as expected, providing the necessary force to the reactions from the neurons. The results came in late December and “everyone thought it was a Christmas present,” recalls Annekeva, “when we got our first hologram, and we could actually see what we predicted theoretically and chemically. The suspect was actually physically true. “

The work is still in its infancy, she says. “It is a very first demonstration that it is possible to use these particles to move large forces to the membranes of neurons to stimulate them.”

“It opens up a whole gamut of possibilities,” she says. … This means that anywhere in the nervous system where cells are sensitive to mechanical forces, and it is essentially any organ, we can now control the function of that organ. “It brings science one 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.

The work was supported by the US Defense Advanced Research Projects Agency, the National Institute of Mental Health, the Department of Defense, the Airforce Office of Scientific Research, and the National Defense Science and Engineering Graduate Fellowship.

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