Mechanobiology

Mechanobiology

Animal tissue grows and remodels in response to changes in mechanical forces. Bones, for example, change shape, density, and stiffness when mechanical loading conditions are altered, hence the need for astronauts in low gravity to exercise or lose bone mass. The cellular components of the tissues are responsible for this remodeling in response to mechanical forces. Such mechanical forces play a fundamental role in the regulation of cell functions, including gene induction, protein synthesis, cell growth, death, differentiation, all of which contribute to tissue homeostasis. Conversely, abnormal mechanical loading conditions alter cellular function and change the structure and composition of the extracellular matrix (ECM), eventually leading to tissue or organ pathologies such as osteoporosis, osteoarthritis, tendinopathy, atherosclerosis, and fibrosis in the bone, cartilage, tendon, vessels, heart, lung, and skin.

A Tensegrity-centered explanation of mechanobiology and its role in disease

Donald E. Ingber is a leading proponent of tensegrity-based modelling of cellular mechanobiology. This summary is based on Donald E. Ingber's "Mechanobiology and diseases of mechanotransduction" from Annals of Medicine 2003;35(8):564-77, 2003, posted by Kevin Parker and blogged at http://adjust2it.wordpress.com/

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.

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.

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.”

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 ExtraCellular Matrix support scaffolds that link cells and tissues throughout the body.”

16) If the ExtraCellular Matrix is less flexible, then stresses will be transmitted to and through the cell.

17) Living cells contain a cytosketeton that generate and transfer tensional forces in a way best comprehended by a “tensegrity” model (Tensegrenous Matrix).

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

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

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.”

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.