Mechanobiology and diseases of mechanotransduction

Posted by:  Kevin G. Parker, D.C.

Annals of Medicine 2003;35(8):564-77. 2003:


Donald E. Ingber, M.D., Ph.D


Mechanobiology and diseases of mechanotransduction.


KEY POINTS

1) “Mechanical forces are critical regulators of cellular biochemistry and gene expression as well as tissue development.”

2) Many “unrelated diseases share the common feature that their etiology or clinical presentation results from abnormal mechano-transduction.”

3) There is an “undeniable physical basis of disease.”

4) Abnormal cell and tissue responses to mechanical stress contribute to the etiology and clinical presentation of many important diseases.

5) There is a “strong mechanical basis for many generalized medical disabilities, such as lower back pain and irritable bowel syndrome, which are responsible for a major share of healthcare costs worldwide.”

6) Physical interventions can influence cell and tissue function. (Manual type therapies, physical therapy, massage, muscle stimulation)

7) “Altered cell or tissue mechanics may contribute to-disease development.”

8 ) “Mechanical forces are critical regulators in biology.”

9) Because of the recent advances in the molecular basis of disease, there has been a loss of interest in mechanics.

10) “Mechanical forces serve as important regulators at the cell and molecular levels, and they are equally potent as chemical cues.”

11) Tissues are composed of groups of living cells held together by an ExtraCellular Matrix (ECM).

12) The surface membrane of cells is mechanically attached to all of the cells organelles, to its nucleus and its chromosomes, and to its synaptic vesicles, by a “filamentous cytoskeleton.” [“Filamentous Cytoskeleton”]

13) Because our bodies are hierarchical structures, mechanical deformation of any tissues results in structural rearrangements in many tissues.

14) Mechanical loads anywhere in the body can affect many tissues and cells because they are physically interconnected.

15) “Forces that are applied to the entire organism (e.g., due to gravity or movement) or to individual tissues would be distributed to individual cells via their adhesions to the ECM support scaffolds that link cells and tissues throughout the body.”  (WOW!)

16) If the ECM is less flexible, then stresses will be transmitted to and through the cell. (WOW!)

17) Living cells contain a cytosketeton that generate and transfer tensional forces, known as “tensegrity.” (Tensegrenous Matrix)

Thomas Myers-Tensegrity Applied to Human Biomechanics 20 min video

18) Changes in the cytoskeletal force balance alter tissue homeostasis.

19) “The physicality of the ECM substrate and degree of cell distortion govern cell behavior regardless of the presence of hormones, cytokines or other soluble regulatory factors.” (WOW!)

20) “Cell-generated tensional forces appear to play a central role in the development of virtually all living tissues and organs, even in neural tissues.”

21) “Mechanical forces directly regulate the shape and function of essentially all cell types.”

22) Many of the enzymes and substrates that mediate cellular metabolism (e.g., protein synthesis, glycolysis, RNA processing, DNA replication) are physically immobilized on the cytoskeleton and nuclear nucleoskeleton matrix. Consequently, mechanical stresses through the cytoskeletal and nucleoskeletal matrix can alter physiology by physically altering biophysical properties, which in turn alter chemical reaction rates.

23) Mechanical stress- stimulates rapid calcium influx in the neuromuscular synapse, again altering function.

24) “All cells also contain ‘stress-sensitive’ (mechanically-gated) ion channels that either increase or decrease ion influx when their membranes are mechanically stressed.”

25) “The global shape of the cell dictates its behavior (e.g., growth versus differentiation or apoptosis), and these effects are mediated through tension- dependent changes in cytoskeletal structure and mechanics.”

26) “These new insights into mechanobiology suggest that many ostensibly unrelated diseases may share a common dependence on abnormal mechanotransduction.” (WOW!)

27) Local mechanical changes in tissue structure may explain why genetic diseases, including cancer, often present focally.

28) Manual type therapies, physical therapy, massage, muscle stimulation, Etc… have known the therapeutic value because they alter mechanotransduction. (WOW!)

29) Most of the clinical problems that bring a patient to the doctor’s office result from changes in tissue structure and mechanics.

30) Abnormal cell and tissue responses to mechanical stress may actively contribute to the development of many diseases and ailments. Consequently it may be wise to look for a physical cause for disease.

31) Mechanics must be reintegrated into our understanding of the molecular basis of disease.

Murphy thoughts:  This is very interesting… this appears to say that as a person loses physical capacity, posture, and control of movement their risk of disease increases.

Below picture: Dense Random scarring of connective tissue

untitled-scanned-11a

Normal connective tissue

Normal connective tissue

Image 1-Excess scar tissue with no motion(stuck joint) #2 shows joint motion=Healthy joint tissue

Image 1-Excess scar tissue with no motion(stuck joint) #2 shows joint motion=Healthy joint tissue

As clinicians… or fitness minded people… this means that everything we do to restore a physical capacity increases their chances of having a more productive and gratifying life with less risk of organic disease.

He appears to say that biochemistry is subservient to tissue structure. If that’s true.. it further reinforces the important role that body posture and movement symmetry play in how well a person performs in daily life, how fast they age, and the quality of life they will have.

This would validate everything we do as practitioners or fitness-minded people dedicated to restoring and maintain the physical body’s form and, therefore, function.

Just think about that. This means that every time we help restore form back to the body its function improves and life becomes just a little bit better.

Great Fascia Video:  Fascia and stretching-The Fuzz Speech-Gil Hedley, Ph.D.

and this…. Fascia-The Secret Life of Fascia-Charles Poliquin 

….More on Donald E. Ingber, M.D., Ph.D-The current focus of medicine on molecular genetics ignores the physical basis of disease even though many of the problems that lead to pain and morbidity, and bring patients to the doctor’s office, result from changes in tissue structure or mechanics.

The main goal of this article is therefore to help integrate mechanics into our understanding of the molecular basis of disease.

This article first reviews the key roles that physical forces, extracellular matrix and cell structure play in the control of normal development, as well as in the maintenance of tissue form and function.

Recent insights into cellular mechanotransduction–the molecular mechanism by which cells sense and respond to mechanical stress–also are described.

Re-evaluation of human pathophysiology in this context reveals that a wide range of diseases included within virtually all fields of medicine and surgery share a common feature: their etiology or clinical presentation results from abnormal mechanotransduction.

This process may be altered by changes in cell mechanics, variations in extracellular matrix structure, or by deregulation of the molecular mechanisms by which cells sense mechanical signals and convert them into a chemical or electrical response.

Molecules that mediate mechanotransduction, including extracellular matrix molecules, transmembrane integrin receptors, cytoskeletal structures and associated signal transduction components, may therefore represent targets for therapeutic intervention in a variety of diseases.

Insights into the mechanical basis of tissue regulation also may lead to development of improved medical devices, engineered tissues, and biologically-inspired materials for tissue repair and reconstruction.

Donald E. Ingber, M.D., Ph.D., has made major contributions to cell and tissue engineering, as well as angiogenesis and cancer research, systems biology, and nanobiotechnology. His research group is interested in how living cells and tissues structure themselves so as to exhibit their incredible organic properties, including their ability to change shape, move, and grow. His team strives to identify design principles that govern the formation and control of living systems, and to use this knowledge to develop novel therapeutics, devices, and robotic systems. By combining approaches from molecular cell biology, chemistry, physics, engineering, computer science, magnetics, and optics, Ingber has helped to develop multiple new experimental nano- and micro-technologies, as well as engineered tissues and cancer therapeutics that have entered human clinical trials. His pioneering work demonstrating that tensegrity architecture is a fundamental principle that governs how living cells and tissues are structured at the nanometer scale has inspired a new generation of cancer researchers, bioengineers, and nanotechnologists. It also has resulted in the discovery of the molecular mechanism by which living cells sense and respond to mechanical forces. His contributions include more than 290 publications and 35 patents in areas ranging from anti-cancer therapeutics, tissue engineering, medical devices, and nanotechnology to bioinformatics software.

Ingber received his B.A., M.A., , M.D., and Ph.D. degrees from Yale University before completing his postdoctoral training with Judah Folkman at Harvard University. He holds the Judah Folkman Professorship of Vascular Biology at Harvard Medical School and Children’s Hospital Boston, and he is a Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences. Ingber served as Co-Director of Harvard’s Center for Integration in Medicine and Innovative Technology at Children’s Hospital from 2005-2007.

He helped to found two biotechnology start-ups, and has consulted for multiple pharmaceutical, biotechnology, venture capital and private investment companies, as well as the Department of Defense, Office of National Intelligence and National Public Radio. Among his many awards and distinctions, Ingber received the Biomedical Engineering Society’s top award for 2009, the Pritzker Distinguished Lectureship, was named one of the world’s “Best and Brightest” in 2003 by Esquire magazine, and is a recipient of a Breast Cancer Innovator Award from the Department of Defense.

Ingber is the Founding Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, which was launched in January 2009 with a $125 million dollar gift — the largest single philanthropic gift in the history of Harvard University.

other related articles: 

Chiropractic Manipulation and Rehabilitation Irvine Calif.  (Janda, Lewit, Liebenson)

Myofascial Release Technique-Active Release Technique (ART)

Manipulation in Improving Motion and Joint Health ~Review of Medical literature

Muscle Trigger points vs Acupuncture points

Thomas Myers-Tensegrity Applied to Human Biomechanics 20 min video:

Posture may Predict Future Disability-J Gerontol A Biol Sci Med Sci. 2013

Sitting Is the New Smoking

Healing Time of Soft Tissue

Back Pain-Insider Secrets revealed-San Fran Gate 2012

A New Gatekeeper for Back Pain

Why Does Back Pain Recur?

Fibroblast cells in Healing

Fish oil-Neurosurgeon for the Pittsburgh Steelers

Foam Roller for Back Pain

Exercise Makes Us Feel Good-NY Times 2011

Gluten Free Diet helped Nerve Pain-Neurology 2010

Inflammation-13 Tips To Fight Inflammation

Laser Therapy in Rehabilitation-Irvine California

Low Back Pain Studies 2010

Magnesium Deficiency

Muscle Trigger points vs Acupuncture points

Neck pain-Journal of the American Board of Family Practice 2004

Nerve ingrowth into chronic painful disc-Lancet 1997

Omega 3’s-Molecular Neurobiology-January 2011

Omega 3′s and Nerve pain-Clinical Journal of Pain 2010

Self Movement Screen

Sitting-Can sitting too much kill you? Scientific American Jan 2011

If you are suffering from: Sports Injuries, Sprains, Strains, Car accident,  Herniated Disc, Disc Bulge, Degenerative Disc Disease, Neck pain, Headaches, Low back pain, of just want to feel better and have better life performance– please call our office in Irvine, California- at 949.857.1888or visit our website at ADJUST2IT to learn more about Functional Fitness Chiropractic, Sports massage, Myofascial Release, Corrective Exercise, Non Surgical Spinal Decompression, Class IV laser,  and Functional Nutrition.

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