Mini microscope is a window into live muscle tissue

New technology lets researchers see motor nerve cells and muscle fibers in action


MUSCLE TWITCH  In a stroke-affected biceps brachii muscle (top), muscle fibers exhibited wiggly contractions over time (x-axis), even though the volunteer was trying to relax. Fibers in the unaffected arm (bottom) held steady, showing no involuntary contractions.

G.N. Sanchez et al/Neuron 2015

Step aside, Fitbit. Data-driven fitness gadgets have nothing on this: A tiny, wearable microscope catches glimpses of muscles in action. The mini microscope, described in the Dec. 16 Neuron, can track minute twitches of most major muscles in live people, a technological feat that was previously impossible.

“It’s an amazing piece of work,” says biomedical engineer Paul Campagnola of the University of Wisconsin‒Madison. This new technology will help scientists better understand how muscles work both in healthy people and in those whose muscles have been affected by stroke, cerebral palsy or other neuromuscular disorders, he says.

Applied physicist and neuroscientist Mark Schnitzer of Stanford University and colleagues had previously designed a large microscope that could image muscle contractions in live people. But that method, described in 2008, was restricted to the forearm, which could fit inside the equipment.

The team’s new tiny microscope can image live muscle action in lots of bodily locales, illuminating previously hidden details about how muscles work, Schnitzer says.   

The microscope fits into the palm of a hand and sits atop a skin-piercing needle. This needle both delivers and collects light, as well as suctions nearby blood to improve visibility. The needle penetrates more than a centimeter deep, and the poke, which is fast, doesn’t hurt, Schnitzer says.

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CAUGHT IN THE ACT A wearable microscope can image contractions of single motor units — a motor nerve cell and the muscle fibers it controls — in live people. G.N. Sanchez et al/Neuron 2015

Once situated, the needle can collect detailed information about skeletal muscle anatomy. For instance, the lengths of sarcomeres, the force-generating units in skeletal muscles, offer clues to how well the muscles work. By measuring sarcomere length in six arm and leg muscles in healthy volunteers, Schnitzer and colleagues now have a more precise view of various muscles’ makeup.

In addition to seeing the structure of muscles, the miniature microscope can also test how well they work. The device stimulates muscle fibers with tiny jolts of electricity and then measures the movements of the sarcomeres, which indicate how the muscle responds. This allowed researchers to see individual motor units — each made of a single motor nerve cell and the muscle fibers it controls — spring into action.

The researchers also tested the microscope on four people who had suffered a stroke that damaged one side of the body. In the affected biceps, muscle fibers spontaneously contracted, producing a wiggly pattern of muscle activity even when the volunteers tried to relax their arms, the team found. The unaffected arms didn’t show these jolts. What’s more, the sarcomere lengths in the stroke-damaged arms were longer than in the unaffected arms, indicating that these muscle fibers might be weaker.

The new microscope provides a more detailed and quantitative way to assess people with muscle problems, says Schnitzer, who along with study coauthors Gabriel Sanchez and Scott Delp, also of Stanford, has started a company based on the technology. “Now we have a lens by which to probe a wide range of neuromuscular syndromes,” Schnitzer says. 

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