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Author ORCID Identifier
https://orcid.org/0009-0003-5813-9267
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Kinesiology
Year Degree Awarded
2023
Month Degree Awarded
September
First Advisor
Edward Debold
Second Advisor
Sam Walcott
Third Advisor
Shuang Zhou
Fourth Advisor
Wouter Hoogkamer
Subject Categories
Atomic, Molecular and Optical Physics | Biological and Chemical Physics
Abstract
In response to repeated intense contractile activity, a muscle’s ability to generate force decreases due to the created state of muscular fatigue. This compromised force production state is dependent on changes within the microenvironment of muscle thought to alter the function of the force generating, contractile protein myosin. For example, phosphate (Pi), elevated during fatigue, has been suggested to alter how myosin generates force. However, the effects of Pi are not straightforward, as muscle fiber data suggest that Pi's interaction with myosin may be force-dependent. In particular, Pi has no effect on maximal shortening velocity, but dramatically decreases isometric force development. These effects of Pi on muscle force development occur in a concentration dependent manner, but the mechanism underlying its effects on myosin has not been resolved. In fact, there are two competing explanations for how Pi reduces the force generating capacity of myosin. Each explanation generates different predictions of how Pi affects myosin. Therefore, to understand the mechanism underlying Pi effects on the crossbridge, we aimed to 1) characterize the force-dependent mechanism of Pi-rebinding in skeletal myosin and 2) identify a structural element coordinating this process. Our work has a) explained the force-dependent effect of Pi on skeletal muscle myosin’s force generating capacity, b) characterized a force sensitive region within the active site that mediates Pi-rebinding, and c) improved our understanding of the mechanisms of muscular fatigue at the crossbridge level.
DOI
https://doi.org/10.7275/35782273
Recommended Citation
Marang, Christopher P., "THE FATE OF THE CROSSBRIDGE AFTER PHOSPHATE REBINDING: IMPLICATIONS FOR FATIGUE" (2023). Doctoral Dissertations. 2899.
https://doi.org/10.7275/35782273
https://scholarworks.umass.edu/dissertations_2/2899
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.