Dissertation
The effect of muscle length and sarcomere length on cross-bridge kinetics in skeletal muscle
Doctor of Philosophy (PhD), Washington State University
01/2020
Handle:
https://hdl.handle.net/2376/112259
Abstract
Skeletal muscles in our arm contract when we lift objects, in our diaphragm when we inhale, and throughout our body to hold a posture. The force underlying contraction is generated by proteins within muscle known as myosin. These motor-proteins form cross-bridges with parallel actin filaments and convert chemical energy into contractile force, which results in sliding of the filaments and shortening of the sarcomere. The in-series shortening of sarcomeres results in shortening of the muscle fiber and eventually the whole muscle. Muscle contraction does not require shortening, however. Muscle force can be counterpoised to the resistive load to provide musculoskeletal stability without muscle movement, and muscles may even lengthen during contraction if the load is greater than the force produced. We know that the force and efficiency of muscle contraction is sensitive to muscle length and contraction velocity, and previous research has suggested that cross-bridge cycling behavior may be strain-dependent. However, whether cross-bridges exhibit strain-dependent behavior in an intact system and how this property contributes to the larger picture of length-dependent muscle behavior remains unclear. Here, we used a combination of novel in-silico and in-vitro methods to investigate the multi-scale relationship between muscle length and cross-bridge kinetics. First, we used a computational model of a half-sarcomere and showed that dynamically shortening the sarcomere decreased force production and increased energy consumption, while lengthening the sarcomere had the opposite effect. Next, we measured myosin kinetics in individual soleus fibers at two different sarcomere lengths. We found that fibers exhibit slower rates of cross-bridge detachment at longer sarcomere lengths due to slowed nucleotide release. Finally, we measured similar kinetics in intact soleus muscle across a range of muscle lengths. Data revealed that cross-bridge detachment is faster at shorter muscle length and slower at longer muscle length. Together, our findings indicate that myosin cross-bridges are sensitive to changes in muscle length over multiple biological scales (from the molecule to the muscle), which may enhance contractility and economy of contraction in response to varying demands on the muscle.
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Details
- Title
- The effect of muscle length and sarcomere length on cross-bridge kinetics in skeletal muscle
- Creators
- Axel Fenwick
- Contributors
- Bert CW Tanner (Advisor)James H Peters (Committee Member)David C Lin (Committee Member)Anita N Vasavada (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Program in Neuroscience
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 142
- Identifiers
- 99900581812301842
- Language
- English
- Resource Type
- Dissertation