Ross Wohlgemuth

UC Davis

“Collagen fibers dynamically re-align in skeletal muscle in response to stretching”

In Duchenne Muscular Dystrophy, there is a nonsense mutation to dystrophin that leads to chronic cycles of damage and accumulation of extracellular matrix (ECM) components, primarily collagen. Collagen fibers are the primary load-bearer of the muscle ECM, and our lab has demonstrated that the architecture of collagen fibers relates to muscle stiffness in dystrophic mice. Previous reports suggest that collagen fiber architecture, specifically collagen alignment, is dynamic during muscle stretching. Additionally, we have found that ex vivo treatment with collagenase, an enzyme mix that digests collagen, was effective in reducing dystrophic muscle stiffness. Thus, we hypothesized that collagen fibers increase their alignment during muscle stretching, which drives increased stiffness, but this re-alignment effect is blunted by collagenase, which results in decreased stiffness. We found that collagen fibers increase their alignment in response to muscle stretching, even after treatment with collagenase. Further, we found that collagen fiber alignment was positively correlated to muscle stiffness. Our results highlight the strain-dependent nature of collagen architecture in skeletal muscle and its relevance to passive stiffness.

ABSTRACT

Skeletal muscles were isolated from healthy and diseased mice and decellularized to remove the cellular material. Decellularized skeletal muscles were measured for stiffness and dynamic changes in collagen fiber alignment with muscle stretching. We found that collagen fibers became highly aligned when the muscle was stretched, and that alignment was correlated to higher muscle stiffness.
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