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Experiments and mechanochemical modeling of smooth muscle contraction: Significance of filament overlap.
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
2012 (English)In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 297, 176-186 p.Article in journal (Refereed) Published
Abstract [en]

The main function of smooth muscle is to maintain/regulate the size of different hollow organs through contraction and relaxation. The magnitude of the active force during contraction is dependent on the number of attached cross-bridges, which can be linked to the overlap between the thin and thick filaments. The relevance of filament overlap and the active cross-bridges in smooth muscle is investigated through a mechanical model founded on Hill's three-element model. The mechanical model describes a sarcomere-equivalent contractile unit supported by structural observations with a distinct filament overlap and a realistic framework for the filament sliding behavior based on force-velocity experiments. The mechanical model is coupled to the four-state latch-model by Hai and Murphy to capture the electromechanical activation from intracellular calcium concentration to load-bearing cross-bridges. The model is fitted to isometric experiments performed on the pig carotid media and on isotonic quick-release experiments found in the literature. The proposed coupled mechanochemical model with the description of the filament overlap, which has a significant influence on the results, is able to predict isometric experimental data performed at different muscle lengths. The relevance of the filament overlap and the load-bearing cross-bridges is investigated through the model by simulating additional scenarios that has been documented in the literature.

Place, publisher, year, edition, pages
2012. Vol. 297, 176-186 p.
Keyword [en]
Smooth muscle, Muscle contraction, Contractile unit, Filament overlap, Modeling
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:kth:diva-66749DOI: 10.1016/j.jtbi.2011.11.012ISI: 000300652000017PubMedID: 22108241Scopus ID: 2-s2.0-84856736341OAI: oai:DiVA.org:kth-66749DiVA: diva2:484610
Note
QC 20120127Available from: 2012-01-27 Created: 2012-01-27 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Mechanochemical Modeling of Smooth Muscle Activation
Open this publication in new window or tab >>Mechanochemical Modeling of Smooth Muscle Activation
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Smooth muscle has an important role in several physiological processes, where it regulates the wall tension and the size of hollow organs. In blood vessels, the contraction and relaxation of smooth muscle contribute to the mechanical stability of the vessel wall and determines the diameter. To better understand how the active tone of smooth muscle influences the passive layers of the artery wall and how dysfunctions of the smooth muscle are related to pathologies such as hypertension and vasospasm, a coupled chemomechanical model based on structural studies and contractile behavior was proposed in this thesis. Smooth muscle contraction arises when cross-bridges between the myosin and actin filament cycle, causing sliding of the filaments. The contraction is triggered when myosin is phosphorylated by an influx of intracellular calcium ions, which can be initiated through different excitation-contraction pathways.

The proposed model coupled a chemical model, where intracellular calcium ion concentration was related to myosin phosphorylation and the fraction of load-bearing cross-bridges, with a mechanical model which was based on the three-element Hill model. The mechanical model, which described a sarcomeric equivalent contractile unit based on structural observations had been developed and modified in different steps to capture the characteristics of smooth muscle behavior, such as isometric contraction, isotonic shortening velocities and length-tension relationships. The chemical material parameters were fitted to calcium-phosphorylation data found in the literature and the mechanical model was fitted against experiments on swine common carotid media performed at Karolinska Instititet, Stockholm. The final coupled model was implemented into a three-dimensional finite element code to simulate the active tone in a two layered artery exposed to realistic pressure pulses. Simulation results indicated that changes in intracellular calcium amplitudes did not have significant effects while changes in the mean value of the intracellular calcium and in the medial wall thickness had a more significant effect on the mechanical response of the arterial wall.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2012. 34 p.
Series
Trita-HFL. Report / Royal Institute of Technology, Solid mechanics, ISSN 1654-1472 ; 0517
Keyword
Biomechanics, Muscle contraction, Smooth muscle, Contractile unit, Filament overlap, Intracellular calcium, Carotid artery, Mathematical model
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-66780 (URN)
Public defence
2012-02-10, Sal F3, Lindstedtsvägen 26, KTH, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20120127

Available from: 2012-01-27 Created: 2012-01-27 Last updated: 2013-01-14Bibliographically approved

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