# Dynamic collagen architecture influence on mechanics of dystrophic skeletal muscle

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $44,873

## Abstract

Fibrosis, which is the pathologic accumulation of extracellular matrix (ECM), is one of the
main traits of Duchenne muscular dystrophy (DMD) and many other muscle pathologies.
Fibrotic ECM differs from healthy ECM in its structural properties, specifically density,
orientation, and cross-linking, often which resulting in a stiffer ECM compared to healthy
muscle. Excessive stiffness of muscle the cause of muscle contractures that are common
in DMD and other neuromuscular disorders. Similarly, we are also interested in the
collagen architecture and structural differences between fibrotic muscle and healthy
muscle. They hypothesis is that these aspects of collagen architecture are disrupted in
fibrosis and responsible for the increase in stiffness, rather than simply the excess
collagen present. The parent R01 investigates how ECM architecture is organized by
FAPs and also directs FAP fate. Aim 3 of the parents R01 investigates how ECM
architecture influences muscle passive mechanical stiffness in coordination with
microdystrophin gene therapy. However, many aspects of ECM architecture may be
dynamically altered with muscle stretch. As in tendon, we would predict that as tissue
undergoes stretch the collagen fibers would align along the direction of stretch and once
straightened contribute largely to passive force. However, integrated muscle mechanics
with detailed muscle architecture that is necessary to understand how dynamic changes
in muscle architecture dictate mechanical properties has not been demonstrated
previously.
This supplement would address that need by leveraging Gabriel’s technical expertise
and equipment available to design a system that is capable of simultaneously measuring
muscle mechanics while imaging muscle ECM architecture. This is an extension of the
parent R01 through the additional of this technical capability, which would allow
investigation of how deformable the ECM architecture is in the fibrotic condition of
muscular dystrophy along with the extent to which microdystrophin gene therapy
recovers matrix dynamic changes. The primary component of ECM architecture that is
anticipated to change with stretch would be collagen alignment and straightness,
however, the level of interactions and fiber diameter may also dynamically shift. The
overall hypothesis is that collagen architecture is dynamically shifted by muscle stretch,
but that these shifts are decreased in dystrophic muscle, and recovered with early
treatment of microdystrophin gene therapy.

## Key facts

- **NIH application ID:** 11071792
- **Project number:** 3R01AR079545-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** LUCAS R SMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,873
- **Award type:** 3
- **Project period:** 2024-09-19 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11071792

## Citation

> US National Institutes of Health, RePORTER application 11071792, Dynamic collagen architecture influence on mechanics of dystrophic skeletal muscle (3R01AR079545-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11071792. Licensed CC0.

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