What The Cell?

By Andrew Shepherd

A Discussion of the Paper: “Sport Performance and Manual Therapies: A Review on the Effects on Mitochondrial, Sarcoplasmatic and Ca2+ Flux Response” by Regno et al (2021)

All of us think about and discuss with our clients the anatomy and physiology of the regions that we treat during our practice of manual therapies. We talk about muscles and joints, fascia and connective tissues, blood and nerve supply. But how often do we think about what is happening at the cellular level?

The above paper reviews some of the specific cellular effects that may occur with both physical activity and manual therapies and what this may mean for both exercise and treatment types in the context of what is known as mechanobiology.

It is important to note from the outset that there is a paucity of good quality studies on the effects on cell structure and function by manual therapy, which is noted within the paper, so much of the discussion is theoretical in nature and based on what is known about the effects of exercise on the cells, and evidence of the effects of manual therapies on the extracellular matrix, which is extrapolated on to the cells themselves.

The introduction of the paper discusses the types of manual therapies commonly used and the structures they affect in terms of pain, function and athletic performance. It also describes the microscopic effects of mechanical stimulation of cellular structures both endogenous, such as the heartbeat on blood vessel endothelial cells, and exogenous, such as manual therapy on the tissues.

Specifically, the paper focuses on the mechanobiological effects on mitochondria, the sarcoplasmic reticulum and calcium ion flow in muscle cells. An example of a well-known mechanobiological effect is given here: “Wolff’s Law”, which states that bone is laid down in the skeleton where it is needed and reabsorbed where it is not, in a process known as ‘mechanotransduction’ – in this case, the piezoelectric effect. This is where a mechanical load applied to the bone is transduced into an electric effect along the bone membrane, which drives mineral ions, such as calcium, into the bone and increases bone density.

Another well-known mechanobiological process is muscle hypertrophy from exercise, where stress is applied to muscle cells, which induces protein synthesis within the sarcoplasmic reticulum of the muscle cell to produce more muscle fibres that are then able to cope with increasing stress.

At a molecular level, mechanobiological processes within muscle cells drive the flow of calcium ions which are crucial to both muscle fibre contraction and mitochondrial function. 

With regard to the mitochondria, the paper references the effects of exercise and structural stress on the organelles via mechanical forces. These forces are transmitted to the mitochondria through the cytoskeleton which can cause them to fuse to other structures or to undergo fission and split into more mitochondria, in both cases affecting cellular function and adaptation to the stressor.

Calcium ions are important to driving cellular processes due to their high positive charge – flowing across special channels in cell membranes and those of their organelles – creating a potential difference on either side of these membranes and simulates an electrical effect. The paper details how one mechanical effect of a force applied to the mitochondrial membrane can stretch open these ion channels and increase the flow of calcium ions.

The paper goes on to discuss the potential role of manual therapies as a mechanobiological intervention. The previous parts of the paper discussed mechanobiology in terms of exercise so the manual therapy role is largely hypothetical and highly speculative. The authors theorise that if manual therapies can have an effect on the extracellular matrix (ECM), then it’s possible they can also affect cell membranes, cytoskeletons and organelles.

The paper references research on the effects of manual therapies on ECM as changes in fibroblast activity and collagen arrangement. Other research showed effects of manual therapy, such as myofascial release, having an effect on myoblast activity. One study referenced by the paper illustrated the mechanotransductive effects of massage on injured quadriceps and subsequent mitochondrial changes.

Several other studies on the cellular and molecular effects of manual therapy were also included in this section, however the authors noted that all of the papers were of low quality and some included negative effects of manual therapies on cellular function. The tests used in these studies to measure the effects of manual therapies on mechanobiology were also considered by the authors to be either of poor quality, low value clinically or simply impractical.

In conclusion, this paper by Regno et al illustrates that there is a whole micro-universe of cellular biology of which we have only scratched the surface and of which most manual therapists are only vaguely aware and likely spend little time thinking about. It’s important to note that the paper is highly theoretical in its claims of potential effects of manual therapies on cell structure and function. However, it is also important for manual therapists to be aware of the concepts highlighted in the paper and that the effects are plausible and need further research to determine whether there is good evidence for them which could therefore influence the way we practice.

About the Author

Andrew Shepherd is a chiropractor and massage therapist in Mosman, NSW, who believes in treating individuals as more than the sum of their parts.

Cover image by Thanks for your Like • donations welcome from Pixabay

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