Mechanochemical transduction in tissues

It is intriguing to try to analyze if differences in mechanochemical transduction mechanisms could explain why some tissues mineralize normally and others do not. This would make it possible to attempt to analyze why heart valves and vessel walls mineralize abnormally in diseases leading to valvular failure or cardiac insufficiency. 

Although the mechanical behavior of tissues has been studied extensively, we know that interpretation of this behavior is made more complex by the time-dependence, also termed viscoelasticity. Therefore, we examine how the time-dependence can be corrected for in terms of the structural components. The goal of the mechanics sections is to relate mechanical behavior to the composition, arrangement, and environmental conditions that affect each tissue type. Finally, we examine how external forces balance with internal forces to modulate mechanochemical transduction. 

We have presented information on the elastic and viscous stress-strain behaviors for a variety of different ECMs in preparation for relating changes in external loading and mechanochemical transduction processes. In order to determine the exact external loading in each tissue that stimulates mechanochemical transduction processes we must take into account the balance between passive loading incorporated into the collagen network in the tissue and active loading applied externally. Inasmuch as the passive load is different for each tissue and is also a function of age (the tension in tissues decreases with age), the net load experienced at the cellular level is difficult to calculate. 

We know from studies of hypertensive animals that blockage of fluid flow in the arterial system not only increases blood pressure but leads to vessel dilation and increases in wall thickness. There appears to be a direct relationship between external (increased blood pressure) mechanical stimulation and up-regulation of mechanochemical transduction processes by increasing the tensile loads that are placed on collagen fibers. This increase in external mechanical stimulation is then directly transferred to smooth muscle cells within the vessel wall. Increased tensile forces lead to increased activation of MAPK pathways as discussed in Chapter 9. We now have the beginning information that details how external mechanical loading influences tissue growth and development. 

Mechanosensing is used to describe the process by which cells sense mechanical forces. Mechanochemical transduction is the phrase that is used to try to describe the biological processes by which external forces such as gravity influence the biochemical and genetic responses of cells and tissues. Specifically, these responses include stimulation of cell proliferation or apoptosis (death) and synthesis or catabolism of components of the extracellular matrix. These processes cause either increases in chemical energy (conversion of amino acids or other small molecules into macromolecules) or decreases in chemical energy (depolymerization of macromolecules). 

The increased vessel wall diameter and wall thickness seen in blood vessels from hypertensive individuals suggests that increased external tensile loading up-regulates tissue deposition. This observation suggests that mechanochemical transduction processes may play an important role in development of atherosclerosis as a result of elevated smooth muscle wall stresses. 

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