/uploadedImages/Bios/Bump_Christopher.jpgby Christopher J. Bump, DC

Genomics, metabolomics, proteomics, nutrinomics; you have probably heard of these terms. Since the completion of the Human Genome Project in 2001 medical science has made exponential advances in understanding the biomolecular, biochemical and genetic influences on health and disease. We are grateful for this, but at the same time we have  tunneled further into a risky place where reductionism runs supreme and our patients become the sum of their single nucleotide polymorphisms. Lets face it, defining SNPs is sexy science. Polymerase Chain Reactions (PCR) provide the ultimate assessment tools for evaluating the individual needs of every patient, and I predict that within a few years we will be able to run personalized SNP testing in our offices. Descartes would be pleased. Read More >>

by Christopher J. Bump, DC

Genomics, metabolomics, proteomics, nutrinomics; you have probably heard of these terms. Since the completion of the Human Genome Project in 2001 medical science has made exponential advances in understanding the biomolecular, biochemical and genetic influences on health and disease. We are grateful for this, but at the same time we have tunneled further into a risky place where reductionism runs supreme and our patients become the sum of their single nucleotide polymorphisms. Lets face it, defining SNPs is sexy science. Polymerase Chain Reactions (PCR) provide the ultimate assessment tools for evaluating the individual needs of every patient, and I predict that within a few years we will be able to run personalized SNP testing in our offices. Descartes would be pleased. 

I wonder though if you are familiar with the term “mechanomics”, which, perhaps, is the most comprehensive example of a systems biology approach in medical science. Dr. Roger Kamm defines the “mechanome” as the complete mechanical state of a biological system including the distribution of stress in the system, the mechanical properties of each of its sub-elements, as well as the collection of interactions between mechanics (force or stiffness) with ongoing biochemical processes.  Mechanomics is composed of the field of mechanobiology which has also seen accelerated growth of discoveries in the past decade. Mechanobiology and mechanotransduction represent multifaceted disciplines between physics, chemistry, biology and bioengineering. These sciences represent the interface and integration of structure and function and have important clinical implications in diseases such as cancer, asthma, malaria and heart disease. 

It is now well established that fascia is much more complex and extensive in its function than taught even 20 years ago. It is not a wrapping, supportive envelope that Gray, Netter and others viewed as disposable tissue. Fascia is the tissue that translates mechanical messages into cellular signals. We know that it is a complex and sophisticated system that reaches every organ, gland, tissue and cell in the body. We also know that one of connective tissue’s newly defined functions is communication. The brilliant research of Helene M. Langevin and others, have elucidated the integral role that fascia now plays in human health and disease. Fascia is intertwined with the extra cellular matrix and it is this relation that enables us to understand and appreciate how mechanotherapies have their effect. 

Fascia is composed of numerous cellular components which include fibroblasts, mast cells, adipose cells, plasma cells, leukocytes and macrophages. Elastic, collagen and reticular fibers make up the fibrous part of fascia. The Extra Cellular Matrix (ECM) gives support and structure to the tissue surrounding the cell and is made up of various macromolecules. These include the ground substance, which is noncollagenous, glycoproteins, proteoglycans and extracellular fluid. Fibroblasts are of special interest as they are the principal cell of the connective tissue and are responsible for the synthesis of collagen, elastic and reticular fibers of the ground substance. Fibroblasts respond to stretch and pressure, and may provide the initial stimulus for the healing cascade. Studies have shown that mechanical force can influence fibroblasts and ground matrix macromolecules to alter their chemical and physical properties. With only slight perturbations to the body, these changes occur. In other words, the fascial composition can and will change in response to stresses throughout ones lifetime. For instance, studies that have demonstrated that light, short stretching of muscle and tendon following injury can expedite recovery, but hard, prolonged stretching causes further injury and increased scarring formation. 

The communication of pressure and mechanical stimuli is transmitted through the fascia network into the ECM which is bound, through its proteins, to transmembrane receptors, known as integrin. Integrins bridge the cellular membrane and hence mediate extracellular membrane signaling. Therefore integrins are the connection between extracellular with intracellular. Within the cell is a complex network of microtubules, microfilaments and intermediate filaments that make up the cytoskeleton. And it is the stimulation cytoskeleton that ultimately influences the cellular structure and function. Cellular differentiation, migration and apoptosis are the result. 

In essence, we are a living matrix of molecular relations that permeate our entire body. This interrelation is also known as tissue tensegrity, which is a combination of both tension and integrity. The idea of tensegrity was originally introduced by Buckminister Fuller in 1961. According to Dr. Donald Ingber tensegrity: “refers to network structures that mechanically stabilize themselves through use of a tensile prestress. They are composed of a network of tensed elements (e.g., cables) that tend to pull towards the center; however, they are balanced by a subset of other structural elements that resist being compressed. As a result, the whole structure is placed in a state of isometric tension that makes it strong, resilient and immediately responsive to external mechanical stresses.” In other words, our cells are not like balloons filled with jello, but more like a hi-tech, lite-weight backpacking tent. Our cells live in a state of pretension and when pressure is applied at one point on the cell, it is distributed throughout the cell. Not only does the force transfer evenly throughout the cytoskeleton, it does so instantaneously! (See figure 3 below which is used with permission from Dr. Wang’s paper on mechanotransduction from a distance.)

The implications of this model are great, as cellular movement, growth and death have been shown to be influenced by tensegrity. Additionally, it has been shown that the stiffness or softness of the fascia and ECM has a direct influence on cellular function. Mina Bissell has shown that certain cancers result from hardness in the ECM and its influence on gene expression. Cancer is only one of many conditions and diseases associated with mechanotransduciton and mechanobiology. Other conditions include arthritis, heart disease, diabetes and irritable bowel disease. In all, every major organ system is affected by mechanical stress. It is how we translate the stress that determines the result, and in this area we have much to learn.

The good news is we know that mechanotherapies have a very beneficial affect on our tissue. These include acupuncture, massage therapy, myofascial therapies, physical therapies and chiropractic adjustment. We’ll explore the benefits of these therapies in a future article. In the meantime, drink lots of water, stretch long and steady, exercise regularly and have your body touched!

Molecular Connectivity from the ECM to nucleus

References:

  1. Celluar Mechanotranduction: Diverse Perspectives from Molecules to Tissues. Mohammad R. K. Mofrad and Roger D. Kamm.  Cambridge University Press 2010 2.
     
  2. Fascia: The Tensional Network of the Human Body. Robert Schleip, Thomas W. Findley, Lean Chaitow, Peter A. Huijing. Churchill Livingston Elsevier. 2012
     
  3. The Scienc and Clinical Application of Manual Therapy.  Hollis H. King, Wilfrid Janig, Michael M. Patterson. Churchill Livingston Elsevier. 2011
     
  4. Khan, K.M. and Scott, A. (2009) Mechanotherapy: how physical therapists‘   prescription of exercise promotes tissue
    repair. Br. J. Sports Med. 43, 247–252
     
  5. Ingber, D.E. (2003) Mechanobiology and diseases of mechanotransduction. Ann.Med. 35, 564–577
     
  6. Ingber, D.E. (2005) Tissue adaptation to mechanical forces in healthy, injured and aging tissues. Scand. J. Med. Sci. Sports 15, 199–201
     
  7. Alenghat FJ, Ingber DE. Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins. Sci STKE (www.stke.org/cgi/content/full/OC_sigtrans;2002/119/ 
     
  8. Stamenovic, D. and Ingber, D.E. (2009) Tensegrity-guided self assembly: from molecules to living cells. Soft Matter 5, 1137–1145
     
  9. Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. 
    Nature Reviews. Molecular Cell Biology10.1 (Jan 2009): 75-82.