The wobbly gel mat trains the muscle cells to work together

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Skeletal muscle fibers. Credit: Berkshire Community College Bioscience Image Library / Public domain

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Skeletal muscle fibers. Credit: Berkshire Community College Bioscience Image Library / Public domain

There is no doubt that exercise is good for the body, including strengthening and toning our muscles. But how exactly does exercise do this?

When we run, lift, and stretch, our muscles experience chemical signals from surrounding cells, as well as mechanical forces acting against the tissue. Some physiologists wonder: Are the body’s natural chemical triggers or the physical forces of repetitive motion — or some combination of the two — ultimately driving our muscles to grow? The answer is key to identifying treatments to help people recover from muscle injuries and neurodegenerative disorders.

Now, MIT engineers have designed a type of workout mat for cells that can help scientists zero in on the microscopic, purely mechanical effects of exercise. They have Published Their results in the journal device.

The new design is no different from a yoga mat: both are rubbery, slightly stretched. As for the MIT mat, it’s made from hydrogel—a soft, Jell-O-like material that’s embedded with foot-sized and magnetic microparticles.

To activate the mechanical action of the gel, the researchers used an external magnet underneath the mat to move the embedded particles back and forth, shaking the gel like a vibrating mat. They controlled the frequency of the wobble to mimic the forces experienced by the muscles during actual exercise.

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They next grew a carpet of muscle cells on the surface of the gel and activated the movement of the magnet. Then, they studied how the cells responded to „exercise” as they were vibrated magnetically.

This video depicts Magnetic Matrix Actuation (MagMA). Credit: Brandon Rios and Angel Bu from the Raman Laboratory at MIT

So far, the results suggest that regular mechanical exercise can help muscle fibers grow unidirectionally. These aligned, „exercised” fibers can work or contract in sync. The findings demonstrate that scientists can use a new workout gel to shape how muscle fibers grow. With their new device, the team plans to design sheets of strong, functional muscle that can potentially be used in soft robots and repair diseased tissue.

„We hope to use this new platform to see if mechanical stimulation can help muscles regrow after injury or reduce the effects of aging,” says Ritu Raman, Britt and Alex D’Arbeloff Professor of Career Development in Engineering Design at MIT. „Mechanical forces play a very important role in our bodies and the environment we live in. Now we have a tool to study it.”

On the bottom mat

At MIT, Raman’s lab designs living materials for use in medicine and robotics. The group is engineering functional, neuromuscular systems with the aim of restoring movement in patients with motor disorders and operating soft and adaptive robots. To better understand natural muscles and the forces that drive their function, his team studies how tissues respond at the cellular level to various forces, such as exercise.

„Here, we wanted a way to disentangle the two main components of exercise, the chemical and the mechanical, to see how the muscles fully respond to the mechanical forces of exercise,” Raman says.

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The team sought a way to expose muscle cells to regular and repetitive mechanical forces while not physically damaging them in the process. They eventually landed on magnets as a safe and non-destructive way to generate mechanical forces.

For their prototype, the researchers created tiny, micron-sized magnetic strips by mixing commercially available magnetic nanoparticles with a rubbery, silicone solution. They cured the mixture to form a slab, then cut the slab into very thin bars. They sandwiched four magnetic strips, each spaced slightly between two layers of hydrogel—a material commonly used to grow muscle cells. The result was a magnet-embedded mat the size of a foot.

The team then grew a „cobblestone” of muscle cells across the surface of the mat. Each cell began as a round shape that gradually elongated and joined with other neighboring cells to form filaments over time.

Finally, the researchers placed an external magnet in a track under the gel mat and planned to move the magnet back and forth. The embedded magnets move in response, shaking the gel and generating forces similar to those experienced by cells during actual exercise. The team mechanically „exercised” the cells for 30 minutes a day, for 10 days. As a control, they grew cells on the same mat but left them to grow without exercise.

„Then, we zoomed in and took an image of the gel and found that these mechanically stimulated cells looked very different from the control cells,” Raman says.

Cells are synchronized

The team’s experiments revealed that muscle cells that were continuously exposed to mechanical movement grew longer compared to unexercised cells, which remained circular in shape. What’s more, the „exercised” cells grew into unidirectionally aligned filaments, whereas non-exercised cells resembled a highly disordered haystack of misaligned filaments.

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The muscle cells the team used in this study were genetically engineered to contract in response to blue light. Normally, muscle cells in the body contract in response to an electrical impulse from a nerve. However, electrically stimulating muscle cells in the lab can damage them, so the team chose to genetically manipulate the cells to contract in response to a noninvasive stimulus—in this case, blue light.

„When we shine light on muscles, you can see the control cells pulsing, but some fibers pulsate this way, some that way, and overall create a very asynchronous pull,” explains Raman. „With fibers aligned, they all pull and hit in the same direction, at the same time.”

Raman says the new workout gel, which he calls MagMA for Magnetic Matrix Actuation, could act as a quick and non-invasive way to shape muscle fibers and study how they respond to exercise. He also plans to grow other cell types in the gel to study how they respond to regular exercise.

„There is evidence from biology that many types of cells respond to mechanical stimulation,” says Raman, „and this is a new tool to study interactions.”

More information:
Extracellular matrices that enable mechanically programming anisotropy in engineered muscle, device (2023) DOI: 10.1016/j.device.2023.100097.

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