Collagen content does not alter the passive mechanical properties of fibrotic skeletal muscle in mdx mice

Lucas R. Smith, Elisabeth R. Barton

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Many skeletal muscle diseases are associated with progressive fibrosis leading to impaired muscle function. Collagen within the extracellular matrix is the primary structural protein providing a mechanical scaffold for cells within tissues. During fibrosis collagen not only increases in amount but also undergoes posttranslational changes that alter its organization that is thought to contribute to tissue stiffness. Little, however, is known about collagen organization in fibrotic muscle and its consequences for function. To investigate the relationship between collagen content and organization with muscle mechanical properties, we studied mdx mice, a model for Duchenne muscular dystrophy (DMD that undergoes skeletal muscle fibrosis, and age-matched control mice. We determined collagen content both histologically, with picosirius red staining, and biochemically, with hydroxyproline quantification. Collagen content increased in the mdx soleus and diaphragm muscles, which was exacerbated by age in the diaphragm. Collagen packing density, a parameter of collagen organization, was determined using circularly polarized light microscopy of picosirius redstained sections. Extensor digitorum longus (EDL and soleus muscle had proportionally less dense collagen in mdx muscle, while the diaphragm did not change packing density. The mdx muscles had compromised strength as expected, yet only the EDL had a significantly increased elastic stiffness. The EDL and diaphragm had increased dynamic stiffness and a change in relative viscosity. Unexpectedly, passive stiffness did not correlate with collagen content and only weakly correlated with collagen organization. We conclude that muscle fibrosis does not lead to increased passive stiffness and that collagen content is not predictive of muscle stiffness.

Original languageEnglish (US)
Pages (from-to)C889-C898
JournalAmerican Journal of Physiology - Cell Physiology
Volume306
Issue number10
DOIs
StatePublished - May 15 2014
Externally publishedYes

Keywords

  • Collagen
  • Fibrosis
  • Passive mechanics
  • Skeletal muscle

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

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