MIT scientists have developed a microfluidic chip that mimics the neuromuscular connections that exist at the junction between neurons and the muscles. These junctions are often involved in various debilitating neuromuscular conditions such as myasthenia gravies and amyotrophic lateral sclerosis (ALS). Studying these junctions under controlled conditions and being able to test various compounds on them may help identify therapies to treat these diseases.
The microfluidic device hosts a single muscle fiber that’s connected to a number of neurons. The three-dimensional space includes sections that separate the nerves from the muscle fibers, just as in our bodies but at shorter distances. In order to improve how closely the device mimics the body, the neuron cells and muscle fibers are also suspended within a special gel that acts kind of like nearby tissue to keep the living components hanging instead of simply laying on a surface.
To grow a muscle fiber, the team used muscle precursor cells obtained from mice, which they then differentiated into muscle cells. They injected the cells into the microfluidic compartment, where the cells grew and fused to form a single muscle strip. Similarly, they differentiated motor neurons from a cluster of stem cells, and placed the resulting aggregate of neural cells in the second compartment. Before differentiating both cell types, the researchers genetically modified the neural cells to respond to light, using a now-common technique known as optogenetics.
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 [Sebastien Uzel, team lead on the study while he was a grad student at MIT’s Department of Mechanical Engineering] 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.
Study in journal Science Advances: Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units