Concepts such as biotensegrity and mechanotransduction have been researched thoroughly and definitively demonstrated through many studies by numerous scientists over the last 25 years. Tensegrity emphasizes the interplay between tension and compression in all structures; and biotensegrity allows us to look at this interplay in biological structures from the gross anatomy level down to the cellular level. Donald Ingber of Harvard has become the most well known researcher on mechanotransduction or the mechanism by which cells convert external mechanical signals into internal biochemical reactions. “Mechano-responsiveness is a fundamental feature of all living tissues.Experiments with cultured cells confirm that mechanical stresses can directly alter many cellular processes, including signal transduction, gene expression, growth differentiation, and survival.”(8) The mechanism of this signaling is now known to travel from the extracellular matrix of the connective tissue, which we used to think did not cross into the inner world of each cell and only structurally supported the cell externally, through the cell membrane at “focal adhesion” sites called integrins that act as transmembrane receptors to then form the intracellular cytoskeleton which then crosses the nuclear membrane and forms the nuclear skeleton. Therefore, mechanical signals travel from any area of the body through the connective tissue fascial system directly into the cells and initiate biochemical reactions and gene expression. (9) Another scientist, Paul R. Standley, PhD, noted that numerous clinical studies have supported the efficacy of manual medicine techniques; but, an evidence base for the cellular mechanism underlying why manual medicine techniques are efficacious had been lacking.(10) Therefore, he has been doing numerous studies that involve applying a repetitive motion strain (RMS) to fibroblasts and then analyzing cell shape, proliferative capacity, cellular protein content, protein-DNA ratio, nitric oxide secretion and cytokine secretion. He chose to study the fibroblast because this is the primary cell of the fascia that is routinely subjected to mechanical forces during normal physiologic movement, pathologic movement and manual medicine techniques. “This makes fibroblasts uniquely poised to affect the amount and types of extracellular matrix proteins, neuromuscular modulators, cytokines and vasoactive molecules secreted into the myofascial matrix.” (11)
In one study Dr. Standley and his team investigated human fibroblast proliferation and interleukin secretion in response to modeled repetitive motion strain (RMS) and modeled indirect osteopathic manipulative techniques (IOMT). The fibroblasts were exposed to one of three conditions: (1) an 8-hour RMS; (2) a 60-second IOMT; (3) an 8-hour RMS followed by a 60-second IOMT. Data on fibroblast proliferation and interleukins present in media were obtained immediately after RMS and 24 hours after each of the experiment conditions. They found that numerous proinflammatory interleukins, such as IL-1a, IL-1B, IL-2, IL-3, IL-6, and IL-16, were substantially increased 24 hours after strain cessation. But, those that had received the 60-seconds of IOMT did not display an increase in these interleukins. Cytokines are not typically stored as vesicle bound proteins; instead they are secreted in a regulated manner only after cellular activation and subsequent gene transcription. (12) Therefore, Dr. Stanley’s studies have shown not only that mechanotransduction does indeed have an effect on gene transcription, but have also begun to demonstrate that “strain regulation of interleukin secretory profiles provides a compelling cellular mechanism to explain injury-induced inflammation and the clinical efficacy of OMT.” (13)
8. Chen, Christopher and Ingber, Donald, “Tensegrity and mechanoregulation: from skeleton to cytoskeleton, Osteoarthritis and Cartilage (1999) 7, pg.81
9. ibid, pg. 81-94
10. Meltzer, Kate, MS and Standley, Paul, PhD; “Modeled Repetitive Motion Strain and Indirect Osteopathic Manipulative Techniques in Regulation of Human Fibroblast Proliferation and Interleukin Secretion”; JAOA, Vol. 107(12), 2007: 527-536.
11. Dodd JG, Good MM, Nguyen TL, Grigg AI, Batia LM, Standley PR; “In Vitro Biophysical Strain Model for Understanding Mechanisms of Osteopathic Manipulative Treatment”, JAOA, 106(3): 157.full. quote pg. 158
12. Meltzer, Kate, MS and Standley, Paul, PhD; “Modeled Repetitive Motion Strain and Indirect Osteopathic Manipulative Techniques in Regulation of Human Fibroblast Proliferation and Interleukin Secretion”; JAOA, Vol. 107(12), 2007: 527-536.
13. Ibid., pg. 534.q11