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Titin contribution to active muscle

Jeong, Siwoo (2021) Titin contribution to active muscle. Doctoral thesis, Northern Arizona University.

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Abstract

The aim of this dissertation is to compare the traditional ‘muscle as motor’ viewpoint to the alternative viewpoint ‘muscle as composite material’. We make three parts to achieve the aim. We first investigate whether the contribution of activation and length perturbation on muscle force depends on length history. The effect of length history is to alter muscle stiffness. The alteration of muscle stiffness determines the role of activation and length perturbation in determining muscle force. That is, muscle responds to activation and length perturbation depending on length history. Muscle models based on the ‘muscle as motor’ viewpoint fail to predict muscle force accurately under dynamic conditions in part because they cannot account for the history dependence of muscle force. An alternative muscle viewpoint should be able to explain the history dependent muscle force to enlarge our knowledge about how muscle works under dynamic conditions. In the second part, we focus on the ratio of muscle force to stiffness. The ratio of force to stiffness has been believed to be relatively constant during isometric contraction because both isometric force and stiffness are linearly related to the number of formed cross-bridge. However, the ratio depends on shortening velocity as well as is not constant during the isometric force redevelopment period following active shortening. This finding invokes ‘stress-induced inhibition’ where weakly-bound cross bridge generated by active shortening contributes only to stiffness with no contribution to force. The weakly-bound cross bridge is able to explain non-zero y-intercepts of the relationship between force and stiffness, but not the lower slope for the slower velocity. In the ‘stress-induced inhibition’, the slower shortening velocity should distort actin more due to the bigger stress. The more distorted actin induces the bigger number of weakly-bound cross bridge, which should result in the bigger slope of the relationship between force and stiffness. This is not compatible with our results. Another possible explanation of the finding is a change in titin stiffness. According to the winding filament hypothesis, titin equilibrium length is modulated by cross-bridge force. Active shortening at different velocity could generate the different initial conditions for titin strain and equilibrium position, and then titin differently responds to an increase in cross bridge force depending on the initial conditions. The tunable titin stiffness contributes to the variable muscle stiffness. Finally, this dissertation develops a titin-clutch model based on a composite material viewpoint. The titin-clutch model predicts frequency-dependent muscle force better than the Hill model. The model has three subunits: a contractile, titin, and series elastic element. The pulley connects the titin to the contractile element in series and parallel. The history-dependent pulley position implements the history-dependent contributions of length perturbation and activation to force. When the contractile force increases, pulley rotates counterclockwise direction, then titin element wraps around a pulley. The interaction between them regulates titin stiffness. The dissertation concludes that incorporating a tunable titin spring in muscle models improves the predictions of muscle force under dynamic conditions.

Item Type: Thesis (Doctoral)
Publisher’s Statement: © Copyright is held by the author. Digital access to this material is made possible by the Cline Library, Northern Arizona University. Further transmission, reproduction or presentation of protected items is prohibited except with permission of the author.
Keywords: Muscle; Muscle contraction mechanism; Muscle mechanics; Muscle model; Titin; Winding filament hypothesis
Subjects: Q Science > QP Physiology
MeSH Subjects: A Anatomy > A02 Musculoskeletal System
NAU Depositing Author Academic Status: Student
Department/Unit: Graduate College > Theses and Dissertations
College of the Environment, Forestry, and Natural Sciences > Biological Sciences
Date Deposited: 16 May 2023 22:30
Last Modified: 17 May 2023 08:30
URI: https://openknowledge.nau.edu/id/eprint/5888

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