The Strex Cell Stretching System Helps Advance Research on Space Flight Muscle Atrophy

User Case Study

At Strex, we strive to gain valuable perspectives on our clients’ applications. The following is a case study of our clients at the Redox Biology and Cell Signaling Laboratory at Texas A&M University, Principal Investigator Dr. John Lawler and Assistant Research Scientist Dr. Khaled Kamal, who graciously shared with us their experience with the Strex ST-1400 Cell Stretching System. They are using the system to apply controlled loading and unloading forces and patterns on skeletal muscle cells to investigate muscular atrophy experienced by astronauts in the microgravity of space. Our interview with them has been edited for formatting.

What kind of research does your lab focus on?

For astronauts in space, gravitational forces are very different from those experienced on Earth, posing increased risks of degradation, or ‘atrophy’, on their skeletal muscles in the absence of normal loading and unloading forces. The Redox Biology and Cell Signaling Laboratory is interrogating applied force-driven changes in the signaling and morphology of the cells that organize into myotubes, the precursors of muscle fibers, during muscle development. Dr. John Lawler tells us, “our interest is mechanotransduction, and that’s the ability of a cell to be able to detect and then act upon changes in the mechanical environment.” The Redox Biology and Cell Signaling Laboratory is funded by NASA to advance their understanding of how cells in myotubes interact with their surroundings and how muscles are remodeled as a result. Dr. Kamal clarifies his project, saying, “we try to have a proof of concept about how we can mimic muscle atrophy and muscle hypertrophy and scale to muscle myotubes. This will allow us to understand how we can mimic spaceflight research by NASA.”

The Redox Biology and Cell Signaling Laboratory at Texas A&M University is investigating muscular atrophy seen in astronauts after spaceflight.

What major issue in healthcare is your lab tackling?

Muscles are very sensitive to their environment, making them susceptible to damage caused by pathophysiological or abnormal conditions. “For skeletal muscle and other cells we’re going to be testing, we’re looking at overloading, unloading, and sometimes just disturbances in the mechanical environment that causes remodeling that usually leads to disease,” states Dr. Lawler. These disturbances are commonly seen with diseases like muscular dystrophy, but he highlights how his laboratory is investigating them as a consequence of space flight. One potential devastating outcome for astronauts is muscle atrophy, where muscle build-up and break-down, or ‘anabolism’ and ‘catabolism’ respectively, become disbalanced. “Catabolism always precedes anabolism. You get rid of the old stuff before you put it together. It’s no different than basically doing some refurbishing and remodeling of your home,” he explains. “That’s exactly what the body is trying to do with skeletal muscles and connective tissue. It happens within weeks in skeletal muscle. It’s highly dynamic.” When the process is out of balance, the muscle may break down or fail to form properly.

Integrative Model of Mechanobiology of the unloading phenotype in skeletal muscle and regulation of RANKL and Nox2 assembly when exposed to spaceflight microgravity. Updated from Source: Lawler 2021, Int. J. Mol. Sci. 2021, 22, 3252.

How has the Strex Automated Uniaxial Cell Stretching System helped you in your research?

The Strex Automated Uniaxial Cell Stretching System, model ST-1400, can apply uniform uniaxial stretching of up to 20% to monolayer cells, tissue and tissue slices, and 3D cultured cells over the course of hours and even days in an incubator. The lab has found that the ST-1400 is ideal for modeling forces applied to muscles in physiological and pathological conditions. “We use the ST-1400 in our skeletal muscle model,” says Dr. Kamal. After the effortless setup out of the box, they were ready to start stretching myocytes. “The Strex cell system allows us to basically kind of break it down to brass tacks in terms of isolating just the mechanical stress on a tissue through stretch, and then coming back and, piece by piece, integrating the system back in,” Dr. Lawler explains.

Dr. Kamal’s proof-of-concept paper (npj Microgravity, DOI: 10.1038/s41526-023-00320-0) demonstrating how myotubes change in size in response to stretch, or lack thereof, is approved for publication in Nature in April 2024. He tells us that “we validate our protocol using immunofluorescence to determine the myotube diameter and signaling and the extent of muscle hypertrophy and atrophy.” His immunofluorescence images show dramatic differences in myotubes undergoing different stretch protocols in the ST-1400. Dr. Kamal explains that “the diameter of the myotube starts to increase in response to only 2 days of cyclic stretching, and after 5 days it becomes even larger. When we had cessation of stretching for 3 days we found a significant decrease in the myotube diameter compared to 2 days and 5 days of stretching.” These findings could have major implications for astronauts in space undergoing long-term absences of the loading and unloading forces experienced by their muscles on Earth. Dr. Lawler hints that there is hope, however. The muscle’s mechanotransduction may be useful in developing therapies to address atrophy. “Mechanical unloading is really a biological response to an anticipated systemic problem,” he tells us. “What we’re trying to do is trick connective tissues, and technically even skeletal muscle, into recovering faster by using biologics, like natural compounds and antibodies.”

Following days of uniaxial stretching in the ST-1400, myotubes are much larger compared to those where stretching has ceased.
Source: Kamal 2024, npj Microgravity, DOI: 10.1038/s41526-023-00320-0.

Why did you choose the Strex ST-1400 over other options?

Controlling the way stretch forces are applied to muscle cells and myotubes is important, Dr. Lawler explains. “Skeletal muscles are different, they mostly see tension as a systemic force. When a load is being put on and stretches a muscle like the biceps, and when that muscle is contracting, that’s actually where a lot of the good stuff happens in terms of stimulation and self-signaling.” In the past, the lab had tried a vacuum-pump stretching device that drew down elastic membranes to stretch cells. “The vacuum system induces what we call radial stretch. In other words, the directions are all over,” he recounts. 

The ST-1400 Cell Stretching System can automatically apply uniaxial stretch to cells.
Source: Kamal 2024, npj Microgravity, DOI: 10.1038/s41526-023-00320-0.

This presented a major roadblock in the project.“The problem is we couldn’t get that uniaxial stretch. And you notice that when you get that uniaxial stretch the muscle fibers all line up like they would do in an actual tissue. The uniaxial stretch lines up those fibers. We get a nice dense population.” With the automated uniaxial stretching of the ST-1400, the Redox Biology and Cell Signaling Laboratory is able to more closely model the isotropic forces experienced by skeletal muscle cells in vivo. “We wouldn’t have that confidence if we had a vacuum system,” Dr. Lawler tells us.

What does the future hold for your research?

With a proof-of-concept paper on the way, the team shares their exciting ideas for further research, including targeting muscle cell mechanotransduction proteins. “We’re going to start using inhibitors and activators to try to tease out which of these proteins, or series of proteins, is most important,” says Dr. Lawler. He tells us that the lab is also interested in interrogating sex-related differences using the ST-1400. “Women tend to lose more muscle mass in a space flight environment. There’s some enhanced stress proteins and other protected proteins that women have in abundance. Some of this is due to estrogen. This allows us to be able to introduce this into the system integrated into stretch.” Further down the line, the lab is considering Strex’s Microscope-Mountable Automated Stretching Systems. Dr. Kamal tells us that “we had the idea how we can implement a microscope for live imaging during the Strex cell stretching” to observe the cells in real time. Eventually, they would like to test the effects of different stretch parameters on muscle cells in space, and examine the influence of microgravity on skeletal muscle.

The team at Strex would like to thank Dr. John Lawler and Dr. Khaled Kamal at the Redox Biology and Cell Signaling Laboratory of Texas A&M University for taking the time to share their story with the ST-1400 Automated Uniaxial Cell Stretching System. Check out their lab’s website for more information on their research. Click here to learn more about Strex’s Cell Stretching Systems and other products. Feel free to reach out and see how we can help you set up your stretching experiments, or click below to request a demo of our products.