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Dissertation/Thesis Abstract

A treatise on theoretical and computational mechanobiology in myosin motors and bacterial cell division
by Lan, Ganhui, Ph.D., The Johns Hopkins University, 2009, 314; 3340039
Abstract (Summary)

This dissertation focuses on theoretical and computational study of several mechanobiological systems, including myosin motors and bacterial cells. The techniques applied in this study are mainly from elasticity theory and statistical mechanics, but need to be further developed to be applicable. To this end, we first comprehensively analyze myosin processivity and prokaryotic cytokinesis, and then propose new treatments for those complex problems based on a mechanobiological point of view.

For the myosin motor system, we propose that conformations of the motor control its ATPase activity, and the probability for the motor to be in various conformations is determined by the structural deformation energy. Treating myosin as a combination of several elastic elements, we compute the deformation energy and adjust motor kinetics accordingly. This treatment successfully explained the processivity of myosin-V and VI. Furthermore, the same framework can be applied to the sarcomere, an ordered array of myosin motors in muscle, by coupling ∼150 myosin motors together. A molecular explanation of skeleton muscle physiological performance is revealed. Our model suggests and confirms that mechanical energy regulates single myosin motor behavior, and the regulated motor kinetics together with the mechanical coupling in muscle structure synchronize the myosin array.

For bacterial cells, we are interested in FtsZ ring driven cell division. We first explore the morphological process during bacterial cell division, and develop a mathematical theory for self-modifying cylindrical shell with anisotropic elastic properties. We quantitatively evaluate contributions from mechanical and biochemical factors during division and conclude that biochemical activity of the cell wall is the dominant contributor. Cell shapes and division velocities are computed. We study the FtsZ ring contraction and force generation. A kinetic model that includes fragmentable single- and double-strand FtsZ filaments is developed to explain in vitro FtsZ polymerization. FtsZ protein self-interaction energies are computed and used to construct a lattice model for in vivo FtsZ division ring formation and contraction. We calculate the force during division and show that lateral interaction induced FtsZ condensation is the origin of force generation.

Indexing (document details)
Advisor: Sun, Sean X.
School: The Johns Hopkins University
School Location: United States -- Maryland
Source: DAI-B 69/12, Dissertation Abstracts International
Subjects: Mechanical engineering, Biophysics
Keywords: Cell division, Myosin motors, Peptidoglycans
Publication Number: 3340039
ISBN: 978-0-549-94017-3
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