# In tendons, differing physiological requirements lead to distinct patterns of MMP-1 degradation

## TL;DR

Energy-storing tendons are more resistant to MMP-1 degradation compared to positional tendons, which may explain their lower collagen turnover and higher injury rates.

## Contribution

The study validates that energy-storing tendon fibrils are more resistant to MMP-1 degradation, particularly in smaller diameter fibrils.

## Key findings

- Energy-storing tendon fibrils showed only a 15% diameter reduction after MMP-1 treatment, compared to a 41% reduction in positional tendon fibrils.
- Larger fibrils experienced greater diameter decreases and more longitudinal variation when exposed to MMP-1.
- Crosslinking is suggested to contribute to the resistance of energy-storing tendon fibrils to enzymatic degradation.

## Abstract

Collagen fibrils from high-stress, energy-storing tendons critical to locomotion are smaller in diameter with increased intermolecular crosslinking compared to fibrils from low-stress, positional tendons. This results in distinct loading mechanics thought to limit fatigue damage in energy-storing tendons. However, there appears to be a functional trade-off with energy-storing tendons also having reduced remodeling ability. Energy-storing tendons have lower collagen turnover and increased injury rates compared to positional tendons. In a recent study, a causative factor for this lower collagen turnover was suggested: resistance to degradation by MMP-1. To validate the prior study’s results obtained from single fibrils, the current study undertook population level assessment of fibril degradation by MMP-1. Predictive degradation models were created to assess fibril diameter distribution changes. Positional and energy-storing tendon sections were incubated for 24 h with buffer or MMP-1, imaged with scanning electron microscopy, and analysed with a custom pipeline for piece-wise fibril measurement. Enzyme treated sections showed evidence of degradation with reduced fibril diameter, decreased alignment, increased curvature, and decreased D-band length. Energy-storing tendon fibrils were more resistant to enzymolysis, with only the large diameter fibril subpopulation affected by MMP-1 (15% diameter reduction compared to control), while the entire population of positional tendon fibrils decreased in diameter (41%). Comparison to model predictions confirmed a linear relationship of degradation with fibril size. Larger fibrils experienced greater diameter decreases combined with increased longitudinal diameter variation and D-band decreases. Crosslinking is thought to be responsible for both fibril type and size findings, the latter suggesting higher density crosslinking in the fibril core.

The online version contains supplementary material available at 10.1038/s41598-025-32374-3.