Three Dimensional Stochastic Computer Model of the Skeletal Muscle Half Sarcomere: changes in calcium diffusion caused by the myofilament lattice

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atmire.migration.oldid5838
dc.contributor.advisorMacIntosh, Brian
dc.contributor.authorHolash, Robert John
dc.contributor.committeememberChen, Wayne
dc.contributor.committeememberBarclay, Chris
dc.contributor.committeememberJacob, Christian
dc.contributor.committeememberter Keurs, Henk
dc.date.accessioned2017-08-11T20:35:12Z
dc.date.available2017-08-11T20:35:12Z
dc.date.issued2017
dc.date.submitted2017en
dc.description.abstractIn this thesis a 3-dimensional model of the skeletal muscle myofibril is developed. This model uses a Monte-Carlo based algorithm to simulate diffusion and binding of individual calcium ions (Ca2+) through the skeletal muscle myofibrillar 1/2 sarcomere. This Ca2+ diffusion model is a departure from recent Ca2+ models, which use a series of ordinary differential equations to compute diffusion and binding. The thesis begins with an overview of current understanding of muscle structure and activation. Emphasising the structure of the myofilament lattice (MFL), and our current ability to understand Ca2+ handling within the sarcomere. We build virtual models of the MFL at lengths of 1.8, 2.3, and 2.8 µm, then demonstrate that changes in MFL spacing associated with changes in sarcomere length (SL), affect myosin and actin interaction. Using MCell™ software that incorporates the MFL, we reproduce the experimental and previous simulation results for an averaged calcium transient during a single activation. In addition, our simulation provided data which demonstrate how the MFL affects the diffusion and binding of Ca2+. This simulation model yielded advanced visualizations of this process; two simulation movies of excitation-contraction coupling. Modelling SLs of 1.8 and 2.8 µm we explore how changes in SL can influence the diffusion of Ca2+ following a simulated activation. At the shorter length of 1.8 µm, the greater filament overlap and larger interfilament spacing result in more even diffusion of Ca2+. Conversely, at 2.8 µm there was an anisotropic distribution of Ca2+ with higher [Ca2+] and greater Ca2+ binding to TnC observed closest to the Z-disk. Finally, the position of the triad on the surface of the sarcomere model was altered to replicate amphibian muscle. Moving the triad to the amphibian muscle position increased the [Ca2+] transient by 56 % when compared with the mammalian placement. This change increases [Ca2+] in the centre of the sarcomere model with fewer Ca2+ able to bind TnC.en_US
dc.identifier.citationHolash, R. J. (2017). Three Dimensional Stochastic Computer Model of the Skeletal Muscle Half Sarcomere: changes in calcium diffusion caused by the myofilament lattice (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28434en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/28434
dc.identifier.urihttp://hdl.handle.net/11023/4010
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.facultyKinesiology
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBioinformatics
dc.subjectPhysiology
dc.subjectComputer Science
dc.subject.otherSarcomere
dc.subject.otherStochastic
dc.subject.otherCalcium
dc.subject.otherDiffusion
dc.subject.otherComputer-model
dc.subject.other3-Dimensional
dc.titleThree Dimensional Stochastic Computer Model of the Skeletal Muscle Half Sarcomere: changes in calcium diffusion caused by the myofilament lattice
dc.typedoctoral thesis
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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