Strained Collagen Resists Bacterial Collagenase Degradation

Abstract

Background: Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals, found in tendon, bone, ligament, cartilage, intervertebral disc, skin, blood vessel, and cornea. Tendons have 70-80% dry weight as collagen, and function as dynamic structures which respond to the magnitude, direction, frequency, and duration of physiologic as well as pathologic mechanical loads via complex interactions between cellular pathways and the highly specialized extracellular matrix. This extracellular matrix of tendon is hierarchical structure having collagen fibrils oriented along longitudinal axis of tendon. The theory suggests that the mechanisms which drive the preferential accumulation of collagen of loaded tissue are not only cell-driven but operate at the molecular level. The concept reduces control of matrix morphology in degrading chemical environment via mechanical strain. Methodology: The investigation was carried out in an environmentally-controlled microbioreactor in which fascicle extracted from mice tail tendon was subjected to strain gradients using three-point bending. The unstrained fascicle was labelled with dye and stripes were created on it via photobleaching. The deformation of fascicle lead to change in the displacement between stripes which resulted in quantification of strain magnitude. Thereafter, deformed fascicle was exposed to bacterial collagenase (BC) and its degradation was tracked using Second Harmonic Generation (SHG) signal produced by collagen fibrils present in it. It was found that mechanical strain significantly increased degradation time of Collagen fibrils present in the regions of fascicle having high tensile strain compared to the ones having low strain magnitudes. Conclusions/Significance:Our study demonstrates for the first time that applied mechanical strain preferentially preserves collagen fibrils forming tendon tissue in the presence of a pathologically-important BC. Our results have the potential to extend our understanding of phenomena like development, adaptation, remodeling and disease of many collagen matrices.