Graduation Term

Fall 2024

Degree Name

Master of Science (MS)

Department

School of Biological Sciences

Committee Chair

Andrés Vidal-Gadea

Committee Member

Tom Hammond

Committee Member

Martin Engelke

Committee Member

Kyle Floyd

Abstract

Muscle tissues generate force, allowing organisms to move and perform mechanical work. To adapt to development, environmental stress, and disease, muscle fibers exhibit plasticity. However, the mechanisms that enable muscles to detect and respond to mechanical load remain unclear. Studies suggest that muscles express mechanosensitive and structural proteins, including PIEZO1, a key mechanoreceptor in striated muscle, and dystrophin, encoded by the DMD gene, which is crucial for mechanical stability. Dystrophin deficiency leads to Duchenne Muscular Dystrophy (DMD), a severe degenerative disease.

This MS thesis explores how mechanosensory proteins like PIEZO1 detect mechanical load changes and regulate structural proteins like dystrophin. Using Caenorhabditis elegans, where PEZO-1 and DYS-1 (the orthologs of PIEZO1 and dystrophin) are expressed in muscle, a combination of anatomical, molecular, and physiological approaches was employed. Loss of dys-1 induces dystrophic phenotypes resembling DMD. An anatomical evaluation revealed multiple types of muscle growth, including allometric, developmental, activity-dependent hypertrophy, and disease-associated atrophy, which parallel those seen in human muscles. This underscores C. elegans as a relevant model for muscle research. Furthermore, PEZO-1 was found to differentially regulate motor patterns, indicating that mechanoreception is finely tuned to functional contexts within muscle. A functional interaction between PEZO-1 and DYS-1 was also identified, highlighting their joint role in maintaining muscle integrity under varying mechanical loads. This work provides new insights into muscle plasticity, function, and adaptation in both healthy and diseased states.

Access Type

Thesis-Open Access

Available for download on Friday, January 15, 2027

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