Graduation Year

2025

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Science and Management

Reader 1

Jenna Monroy

Reader 2

Ashley Heers

Abstract

The goal of this study is to understand titin’s role in muscle fiber type composition in response to resistance exercise. Titin is a long protein with spring-like properties which allows it to play a role in passive force production during muscle activation. Due to its large size and central location in the sarcomere, titin has been linked to many signaling pathways, including hypertrophic signaling. These signaling pathways can influence muscle fiber type, which can be categorized by myosin heavy chain isoforms (most commonly–type I, type IIa, type IIb). Type I fibers are highly oxidative and common in larger muscles used for endurance activities. Type IIb fibers have few mitochondria and fatigue rapidly, but are used in fast, forceful movements. Type IIa is an intermediate fiber and functions between type I and type IIb. This study compared the muscle composition of TtnΔ112-158 mice with a 75% deletion of the PEVK region of titin to wild-type mice at varying physical activity levels. We hypothesize that titin’s spring-like and cell signaling properties are essential to exercise-induced change in muscle composition. Using immunohistochemistry we measured the size (area and diameter) of the muscle fibers and identified the amount/type of fiber (type I, type IIa, or type IIb) within a soleus muscle section of a specimen. Due to the multiple known functions of titin, we have two conflicting expected results. Since titin acts as a molecular spring, a shorter titin protein would require more force for contraction. Therefore, mutant mice may be expected to have more Type IIb fibers to perform exercises. However, because titin also contributes to cell signaling, the TtnΔ112-158 mice presumably have an impaired ability to convert type I fibers to type IIa and type IIb. Therefore, exercise would have less of an effect on the TtnΔ112-158 mice and we would not expect to see many type IIa or type IIb fibers in TtnΔ112-158 mice. Our results showed a decrease in type IIa fiber area in TtnΔ112-158 mice. There was no significant change in the percentage of fiber types in the wild-type and TtnΔ112-158 mice in response to exercise. However, trends in the data show an increase in type IIa fibers in TtnΔ112-158 following resistance exercise. Though the PEVK region of titin plays a role in cell signaling (and is likely linked to hypertrophic signaling) its role as a molecular spring contributes most to its effect on muscle composition during physical activity.

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