Experimental and Theoretical Investigations on the Mechanical Stabilization and Enzymatic Degradation of Collagen.

摘要

The major aim of this dissertation work was to contribute to the current understanding of connective tissue remodeling and deterioration. More specifically, the goal was to test the existence of a relationship between applied mechanical tension and the enzymatic susceptibility of collagenous tissue, which provides the structural backbone for tendons, ligaments, cartilage, and bone, as well as more specialized tissues including vasculature and cornea. This relationship, with mechanical tension slowing the enzymatic degradation of reconstituted collagen tape, was first observed in 1977. In the next decades, several additional studies would show a similar result with mechanical load slowing the enzymatic and thermal degradation of collagenous tissues. While results from tissue-level investigations continued to support the initial observation that mechanical tension reduced enzymatic degradation, the use of bulk tissue obscures extraction of the detailed relationship between applied force and enzymatic degradation rate. The main focus of this work was to unequivocally show that mechanical load slows the enzymatic degradation of collagen, and then to characterize the mechanochemical relationship between force and enzymatic cleavage kinetics. Mechanochemical results are presented from reconstituted bulk fibril experiments as well as isolated, single fibril experiments. Finally a characterization of the relationship observed between force and enzymatic molecular cleavage is provided.