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Title:Cellular strategies for chemotactic navigation in complex chemical environments
Author(s):Kimura, Yuki
Director of Research:Rao, Christopher V.
Doctoral Committee Chair(s):Rao, Christopher V.
Doctoral Committee Member(s):Olson, Luke N.; Kenis, Paul J.A.; Kong, Hyun Joon
Department / Program:Chemical and Biomolecular Engineering
Discipline:Chemical Engineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Multiscale simulation
Abstract:Motility is a fundamental cellular behavior that is often prompted by environmental changes and/or stimuli. In particular, many cells exhibit directed movement in response to soluble chemicals in their vicinity - this phenomenon is commonly known as chemotaxis. Chemotactic cell migration is central to a variety of processes including embryogenesis, tissue development, wound healing and cancer metastasis [1, 2, 3, 4]. The key to this response is the ability of cells to sense spatial and/or temporal variation in the concentration of chemoeffectors (often attractants) diffusing from nearby sources. Since concentration typically decreases with distance from the source (as a result of molecular diffusion), these chemical landmarks can serve as a natural basis for cell navigation, as well as for coordinating large populations from the single-cell level. The ubiquity of such chemical gradients in nature also makes them a reliable choice for this purpose. Understanding how cells detect and respond to chemotactic gradients is an important problem in many areas of biology. To investigate this subject, specialized in vitro techniques - known as chemotaxis assays - have been invaluable in characterizing and quantifying the responsiveness of cells under varied conditions. For instance, Zigmond and Dunn chambers have been used to look at eukaryotic cell motion [5, 6], while capillary assays have been used to study bacterial chemotaxis [7, 8]. These methods have traditionally been applied using simple, single chemoeffector gradients. Recently, however, new studies have exposed additional intricacies in the chemotactic mechanisms of certain cells; these features appear to improve the robustness and efficiency of chemotaxis in the presence of multiple chemical species and/or multiple sources. Such complex, heterogeneous conditions are thought to be a closer represention of the cells’ native environments, and therefore offer a more complete account of the process in physiological settings. The primary goal of this thesis is two-fold. First, I present new results and insight gained from studying cell behavior under the influence of multiple chemotactic stimuli. This is accompanied by mathematical models that are designed to deconstruct the underlying mechanistic principles. Here, I employ a number of computational tools and simulations to demonstrate my key arguments. The second component is a theoretical discussion on how cells navigate and make optimal decisions in such noisy environments. This subject raises a number of interesting questions pertaining to control theory, optimization (e.g. k-armed bandit), foraging theory, and biomechanics. While the ideas presented here may extend to many organisms and cell types, this work examines two representative systems in particular - the bacterium Escherichia coli and a class of mammalian immune cells known as polymorphonuclear neutrophils.
Issue Date:2013-02-03
Rights Information:Copyright 2012 Yuki Kimura
Date Available in IDEALS:2013-02-03
Date Deposited:2012-12

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