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Investigating the concerted release of myosin on regulated thin filaments using single molecule microscopy

Smith, Quentin (2021) Investigating the concerted release of myosin on regulated thin filaments using single molecule microscopy. Master of Research (MRes) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.89379) (KAR id:89379)

Abstract

Contraction and force generation in muscle occurs via interactions between thick and thin filaments within the subcellular sarcomere structure of fused muscle cells (myofibrils). This heavily regulated process involves the coordinated efforts of tropomyosin, the troponin complex, myosin binding protein C and other accessory proteins. The regulation of muscle contraction is important for both contraction and relaxation, for example in the heart, the former leads to pumping and the latter refilling of the cardiac chambers. The focus of this thesis is the relaxation of muscle, which is highly relevant to diseases such as HCM. Using single molecule microscopy, the dynamics of thin filament activation have been measured in a metastable condition, between contraction and relaxation. This provides a molecular insight into both processes at the same time. Here I have developed a suite of analysis programs to investigate how the muscle regulatory system relaxes. Analysis of events has revealed that myosin molecules attached to regulated thin filaments are released in a concerted fashion, a process we call catastrophic collapse. With this understanding and new analytical tools, we are now in a position to analyse mutations associated with HCM to shed light on how these affect the relaxation dynamics of thin filaments in disease.

Item Type: Thesis (Master of Research (MRes))
Thesis advisor: Kad, Neil
DOI/Identification number: 10.22024/UniKent/01.02.89379
Uncontrolled keywords: Biochemistry, Muscles, Myosin II, Single Molecule
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 23 Jul 2021 12:51 UTC
Last Modified: 09 Dec 2022 01:36 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/89379 (The current URI for this page, for reference purposes)

University of Kent Author Information

Smith, Quentin.

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