A new method for mechanical stimulation of nerve cells

Reviewed by Emily Henderson, B.Sc.July 20, 2020

Many nerve cells in the body can respond to electrical and chemical stimuli as well as mechanical effects such as pressure and vibration. However, these responses have become more difficult for researchers to study because there was no easily controllable way to induce mechanical stimulation of such cells. Researchers such as MIT are now discovering new ways to do that.

This finding may provide a step toward new types of treatments, as well as electrical-based nerve stimulation that has been used to treat Parkinson’s disease and other medical conditions. Unlike these systems, which require external wire connections, the new system is completely contactless after the first injection of particles and can be restarted at will through an externally applied magnetic field.

Findings are reported in the journal ACS Nano, Post-doc MIT Danijela Gregurec, Alexander Senko PhD ’19, Associate Professor Polina Anikeeva, Boston Brigham and Women’s Hospital at MIT, and 9 papers in Spain.

New methods open new pathways for stimulating nerve cells in the body. It has relied almost entirely on chemical pathways through the use of drugs, or electrical pathways that require invasive wires to supply voltage to the body. .. The researchers say that this mechanical stimulus may activate completely different signaling pathways within the neurons themselves, providing an important area of ​​study.

“The interesting thing about the nervous system is that neurons can actually detect forces,” says Senko. “That is your sense of touch, and your sense of hearing and balance.” The team targeted a specific group of neurons in a structure called the dorsal root ganglion. It forms the interface between the central and peripheral nervous systems. These cells are particularly sensitive to mechanical forces.

According to Senko, the application of this technology may be similar to that being developed in the field of bioelectronic medicine, but it usually requires larger and stiffer electrodes than the stimulated neurons, and their accuracy It is limited and can damage cells.

The key to the new process was to develop microscopic disks with unusual magnetic properties. This can cause the disc to start flapping when exposed to certain types of fluctuating magnetic fields. The size of the particles themselves is only about 100 nanometers, which is about one-hundredth of the size of the neurons they are trying to stimulate, but because they can be made and injected in large numbers, their effects are collectively A receptor that is strong enough to activate pressure. “We actually created nanoparticles that create the forces that cells can detect and respond to,” says Senko.

Anikeeva said that finding conventional magnetic nanoparticles requires an unrealistically large magnetic field to activate, and finding a material that can provide sufficient force at moderate magnetic activation is a “very difficult problem.” I say yes. The solution turned out to be a new kind of magnetic nanodisk.

These disks, which are hundreds of nanometers in diameter, contain a spiral shape of atomic spins when no external magnetic field is applied. This causes the particles to behave as if they were completely non-magnetic and very stable in solution. When these discs are exposed to a very weak fluctuating magnetic field of a few millitesla, and the frequency is as low as a few hertz, they switch to the state where all the internal spins are aligned with the disc surface. This causes these Nanodiscs to act as a lever and swing up and down in the direction of the field.

Anikeba, an associate professor in the Departments of Materials Science and Engineering and Brain Science and Cognitive Science, found that this research has led to several areas, including new chemistry that led to the development of these Nanodiscs, the field of electromagnetic effects and neurostimulation It is said that it is combined with research related to science.

The team first considered using particles of magnetic metal alloys that could provide the required force, but these were not biocompatible materials and were very expensive. Researchers have found a way to use particles made from hematite, a benign iron oxide that can form the required disk shape. Next, hematite was converted to magnetite. Magnetite has the necessary magnetic properties and is known to be benign in the body. This chemical conversion of hematite to magnetite dramatically darkens the blood red tube of particles.

“We had to make sure that these particles really supported this extraordinary spin state, this vortex,” Gregrec said. They first tried the newly-developed nanoparticles and, using a holographic imaging system provided by a colleague in Spain, the particles responded exactly as expected and the force needed to elicit a response from neurons. Proved to provide. The results were announced in late December, saying, “everyone thought it was a Christmas gift,” when the first hologram was obtained, what was theoretically predicted and chemically suspected was actually physically I actually found it true.

The work is just beginning.

This is the first demonstration that it is possible to use these particles to transform large forces into the membrane of neurons and stimulate them. “

Polina Anikeeva, MIT Associate Professor

She said, “It opens up the whole field of possibilities. This is wherever cells in the nervous system, where cells are sensitive to mechanical forces, and essentially any organ, It means being able to regulate function.” She takes science one step closer and approaches the goal of bioelectronic medicine, which can stimulate at the level of individual organs or parts of the body without the need for drugs or electrodes. say.