Mechanotransduction

Impacting the Body Down to the Cellular Level

By David Lesondak
[Body of Wonder]

Takeaway: Researchers used compression, stretch, and shear to have a regenerative effect on the mechanical environment of damaged cell cultures.

Whatever style of bodywork you do, you’re obviously aware of the potential effect it can have on muscle tissue/tonus, range of motion, nervous-system regulation, hydration, pain management, and even constipation.1 What would you think if I told you the potential effects can impact each individual cell in your body?

Into the Cell

Just as your body has a specific structure, so do your cells. Because of the oversimplified diagrams we saw in grade school, we tend to think of cells as round, microscopic balls, but their shape is much more varied than that. The shape is determined and maintained by a network of three interlinked proteins, including actin and myosin, which are collectively known as the cytoskeleton. However, cells respond to not only chemical changes in their environment (like the caffeine in the green tea I drank to keep focused while writing this article), but also mechanical changes in their environment. These responses to pressure and vibrations can create a host of electrochemical changes in the cell.2 And this, believe it or not, is where practitioners can make a difference.

Like a satellite with numerous antennae orbiting Earth, every cell in your body is similarly festooned with cell receptors that “listen” for different types of messages. The receptor of most interest to us is the integrin. Integrins are incredibly social, connecting cells to other cells and to the individual collagen fibers in the fluid and fiber matrix that we in the macro-bodywork world call fascia. But in the microbiology world, they are the extracellular matrix (ECM). Integrins are transmembrane receptors, meaning they cross intercellular and extracellular boundaries for the purpose of communication. Integrins are found on nearly every cell in your body, but curiously seem to be absent on cancer cells. They also connect to larger intercellular macromolecules called focal adhesions (more on that in a bit). 

Integrins are sensors for mechanical and physiological stress, as you might imagine, since they’re linked to the ECM. They are further linked to the actin filaments in your cytoskeleton and can transmit physical stresses, both good and bad, that cause the cell to change its shape and behavior. Cell yoga, anyone? 

Furthermore, the integrins have a fibrillar network that goes all the way to the nucleus of the cell. Stimulation of the integrins can hasten both cell growth and death, motility, and even gene expression. This process of creating electrochemical changes in the cell via changes in external pressure and tension in the ECM is called mechanotransduction,3 a process that happens at the speed of sound (see image). 

To summarize, the nucleus of every cell in your body is connected via the integrins to your fascial web. That’s about 100 trillion cells for the average adult. All connected. When stimulated, the integrin induces mechanotransduction, which affects the cell’s quality of life at a rate that is almost three times faster than your nervous system. 

Into the Lab

One of my favorite studies that helped establish the cellular evidence base necessary to help explain the positive benefits of manual therapy was done by inducing repetitive motion strain (RMS) in a living cell culture.4 Cells were placed on a flexible petri dish that could be subject to the same mechanical stress over and over for eight hours. For example, take a straw, or your finger, or your back, and bend it the same way, back and forth, for eight straight hours. No, wait. Don’t do that. It turns out that after eight hours of RMS, the cells not only visibly changed, but many of the intercellular connections were damaged or broken, production of noxious cytokines increased, and the rate of cell death (apoptosis) increased by 30 percent—something to think about the next time someone with a mechanically repetitive job comes to see you.

But, as a clickbait headline might read, you won’t believe what happened next! Those same researchers took the damaged cell cultures and changed their mechanical environment, adding the combined elements of compression, stretch, and shear. Basically, they added the three necessary components of what we might, by any other name, call a myofascial release (MFR). They chose an application interval of 60 seconds—a totally random choice, the researchers tell me. And that’s when the astonishing thing happened. It had a regenerative effect on the cells. In fact, it restored the apoptosis rate to normal, as it did the cell morphology (which is the scientific word for shape). The takeaway is that 60 seconds of MFR can undo the damage from eight hours of repetitive motion—on the cellular level at least.

More recently, Bo Ri Seo at Harvard’s Wys Institute for Biologically Inspired Engineering took this a step further.5 She and her team created a sophisticated, tunable, soft robotic “finger” capable of delivering a consistent compression to the leg muscles of mice. They were able to show that this “robotic massage” not only increased the speed with which neutrophils (a type of white blood cell) were removed from the damaged tissue, but also further removed inflammatory cytokines generated by these neutrophils. That further enhances the regeneration of muscle fibers and shows a very clear connection between mechanical stimulation and immune function. 

Onto the Table

Back in the macro world, 11 young men pushed themselves to exhaustion via heavy exercise. They did this to measure the effects of post-exercise massage.6 The muscle chosen for this study was the vastus lateralis. Tissue biopsies were taken before exercise, after a 10-minute massage, and 2.5 hours later. The result? The massage induced mechanotransduction in a number of markers, including reduction of inflammatory cytokines, formation of new mitochrondria (our cellular batteries), and focal adhesion kinase (FAK). FAK is essential to the process of phosphorylation (cellular sugar metabolism, energy storage, and release) and regulates and mediates other intercellular signals too.

So, the next time someone gets off your table and tells you they feel great all the way down to their bones, you can smile and tell them it actually goes a little deeper than that. 

Notes

1. Nuray Turan and Türkinaz Atabek Aşt, “The Effect of Abdominal Massage on Constipation and Quality of Life,” Gastroenterology Nursing 39, no. 1 (January/February 2016): 48–59, https://doi.org/10.1097/SGA.0000000000000202.

2. Thomas Burkholder, “Mechanotransduction in Skeletal Muscle,” Frontiers in Bioscience–Landmark 12, no. 1 (January 2007): 174–91, https://doi.org/10.2741/2057; Daniel Tschumperlin, “Mechanotransduction,” Comprehensive Physiology 1, no. 2 (April 2011): 1057–73, https://doi.org/10.1002/cphy.c100016. 

3. Z. Sun, S. S. Guo, and R. Fässler, “Integrin-Mediated Mechanotransduction,” Journal of Cell Biology 215, no. 4 (November 2016): 445–56, https://doi.org/10.1083/jcb.201609037.

4. Kate Meltzer et al., “In Vitro Modeling of Repetitive Motion Injury and Myofascial Release,” Journal of Bodywork and Movement Therapies 14, no. 2 (April 2010): 162–71, https://doi.org/10.1016/j.jbmt.2010.01.002. 

5. Bo Ri Seo et al., “Skeletal Muscle Regeneration with Robotic Actuation-Mediated Clearance of Neutrophils,” Science Translational Medicine 13, no. 614 (October 2021): https://doi.org/10.1126/scitranslmed.abe8868.

6. Justin Crane, “Massage Therapy Attenuates Inflammatory Signaling after Exercise-induced Muscle Damage,” Science Translational Medicine 4, no. 119 (February 2012): 119ra13, https://doi.org/10.1126/scitranslmed.3002882. 

David Lesondak is an Allied Health member in the Department of Family and Community Medicine at the University of Pittsburgh Medical Center, and is board-certified in structural integration. He is the author of Fascia: What It Is and Why is Matters, editor of Fascia, Function, and Medical Applications, and host of the podcast BodyTalk. Learn more at davidlesondak.com.