Cross-Links Can Harm Tendon Collagen Structure

Cross-links between proteins are formed by advanced glycation end-products and become a growing problem with advancing age. The best understood consequences are the degradation of elasticity in skin and blood vessels, but there are many other forms of harm that result from this interference with tissue structure. There is too little research presently taking place on methods of safely breaking cross-links, but this is something that the SENS Research Foundation seeks to change - the means to make an impact on aging here is one of the forms of rejuvenation treatment that might be developed comparatively rapidly, given the funding.

Here is an example of another form of harm created by cross-links, this time in the structure of tendons. The molecular structure of tissues determines their properties, such as mechanical strength and elasticity, and damage to that structure leads to loss of function:

Recent molecular modeling data using collagen peptides predicted that mechanical force transmitted through intermolecular cross-links resulted in collagen triple helix unwinding. These simulations further predicted that this unwinding, referred to as triple helical microunfolding, occurred at forces well below canonical collagen damage mechanisms. Based in large part on these data, we hypothesized that mechanical loading of glycation cross-linked tendon microfibers would result in accelerated collagenolytic enzyme damage.

This hypothesis is in stark contrast to reports in literature that indicated that individually mechanical loading or cross-linking each retards enzymatic degradation of collagen substrates. Using our Collagen Enzyme Mechano-Kinetic Automated Testing (CEMKAT) System we mechanically loaded collagen-rich tendon microfibers that had been chemically cross-linked with sugar and tested for degrading enzyme susceptibility. Our results indicated that cross-linked fibers were more than 5 times more resistant to enzymatic degradation while unloaded but became highly susceptible to enzyme cleavage when they were stretched by an applied mechanical deformation.



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