New microfluidic chip replicates muscle-nerve connection


MIT engineers have developed a microfluidic device that replicates the neuromuscular junction - the vital connection where nerve meets muscle. The device, about the size of a U.S. quarter, contains a single muscle strip and a small set of motor neurons.
Image: Microfluidic chip; Copyright:

New chip could help test drugs for ALS, other neuromuscular disorders; ©



The team's results, published online today in Science Advances, may help scientists understand and identify drugs to treat amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig's disease, as well as other neuromuscular-related conditions.

"The neuromuscular junction is involved in a lot of very incapacitating, sometimes brutal and fatal disorders, for which a lot has yet to be discovered," says Sebastien Uzel, who led the work as a graduate student in MIT's Department of Mechanical Engineering. "The hope is, being able to form neuromuscular junctions in vitro will help us understand how certain diseases function."



"Think of a giraffe," says Uzel, who is now a postdoc at the Wyss Institute at Harvard University. "Neurons that live in the spinal cord send axons across very large distances to connect with muscles in the leg."



Kamm says light "gives you pinpoint control of what cells you want to activate," as opposed to using electrodes, which, in such a confined space, can inadvertently stimulate cells other than the targeted neural cells.

Finally, the researchers added one more feature to the device: force sensing. To measure muscle contraction, they fabricated two tiny, flexible pillars within the muscle cells' compartment, around which the growing muscle fiber could wrap. As the muscle contracts, the pillars squeeze together, creating a displacement that researchers can measure and convert to mechanical force.

In experiments to test the device, Uzel and his colleagues first observed neurons extending axons toward the muscle fiber within the three-dimensional region. Once they observed that an axon had made a connection, they stimulated the neuron with a tiny burst of blue light and instantly observed a muscle contraction. "You flash a light, you get a twitch," Kamm says.


"You could potentially take pluripotent cells from an ALS patient, differentiate them into muscle and nerve cells, and make the whole system for that particular patient," Kamm says. "Then you could replicate it as many times as you want, and try different drugs or combinations of therapies to see which is most effective in improving the connection between nerves and muscles."

On the flip side, he says the device may be useful in "modeling exercise protocols." For instance, by stimulating muscle fibers at varying frequencies, scientists can study how repeated stress affects muscle performance.

"Now with all these new microfluidic approaches people are developing, you can start to model more complex systems with neurons and muscles," Kamm says. "The neuromuscular junction is another unit people can now incorporate into those testing modalities."; Source: Massachusetts Institute of Technology

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