Mechanochemical transduction processes

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. 

There are a number of biochemical components that are involved in mechanochemical transduction processes. We introduce some of the important molecules in an attempt to demonstrate how complex the mechanisms appear to be however, the functions and interrelationships among these molecules are currently unclear. 

Although mechanosensing and mechanochemical transduction processes are likely to be quite complex from a biochemical point of view, we can begin to understand from an engineering point of view how changes in... 

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. 

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). 

Figure 9.6. Diagram illustrating the pretension present in the superficial zone of articular cartilage. Normal articular cartilage shown at the top is loaded in tension across the surface like a drumhead that is pulled taut over a drum. When a piece of cartilage is cut from the surface, it curls as a result of release of this tension, as shown in the lower diagram. The presence of tension in the superficial zone makes articular cartilage behave like a drumhead, allowing compressive forces applied to the surface at specific points to be distributed across the surface to lower local stresses. The presence of tension on the chondrocytes in the superficial layer may be important to limit inflammation and support reparative processes by stimulating mechanochemical transduction.

Studies involving fluid shear, hydrostatic compression, biaxial and uniaxial stretch, or a combination of two or more of these factors indicate that fluid shear is a major factor affecting bone cell metabolism and cells subjected to mechanical stress reshape and align themselves with their long axis perpendicular to the axis of force. Cells also exhibited remodeling of the actin cytoskeleton and increases in PKC levels, processes thought to be involved in the early phase of mechanochemical transduction. 

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