Cellular strategies for chemotactic navigation in complex chemical environments

Neutrophil;E.coli;Chemotaxis;Multiscale simulation

Kimura, Yuki

关键词: Neutrophil;    E.coli;    Chemotaxis;    Multiscale simulation;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/42183/Yuki_Kimura.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

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 ofprocesses including embryogenesis, tissue development, wound healing and cancer metastasis [1, 2, 3, 4]. Thekey to this response is the ability of cells to sense spatial and/or temporal variation in the concentrationof chemoeffectors (often attractants) diffusing from nearby sources. Since concentration typically decreaseswith distance from the source (as a result of molecular diffusion), these chemical landmarks can serve as anatural basis for cell navigation, as well as for coordinating large populations from the single-cell level. Theubiquity 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 manyareas 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], whilecapillary assays have been used to study bacterial chemotaxis [7, 8]. These methods have traditionally beenapplied using simple, single chemoeffector gradients. Recently, however, new studies have exposed additionalintricacies in the chemotactic mechanisms of certain cells; these features appear to improve the robustnessand efficiency of chemotaxis in the presence of multiple chemical species and/or multiple sources. Suchcomplex, 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 studyingcell behavior under the influence of multiple chemotactic stimuli. This is accompanied by mathematicalmodels that are designed to deconstruct the underlying mechanistic principles. Here, I employ a numberof computational tools and simulations to demonstrate my key arguments. The second component is atheoretical discussion on how cells navigate and make optimal decisions in such noisy environments. Thissubject raises a number of interesting questions pertaining to control theory, optimization (e.g. k-armedbandit), foraging theory, and biomechanics. While the ideas presented here may extend to many organismsand cell types, this work examines two representative systems in particular - the bacterium Escherichia coliand a class of mammalian immune cells known as polymorphonuclear neutrophils.