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Non-Ideal Thermodynamic Models of Cryobiological Solutions and the Intracellular Space

  • Author / Creator
    Zielinski, Michal W
  • Mathematical models of cryopreservation processes are an important tool in the development of cryopreservation protocols that successfully avoid cryoinjury. Theoretical models of solution thermodynamic behaviour, known as solution theories, lie at the core of many cryopreservation models, including those that simulate the cellular osmotic response. However, to provide accurate predictions of solution behaviour, these solution theories must be able to account for the inherent thermodynamic non-ideality of cryobiological solutions. They must also be able to provide predictions in the complex multi-solute solutions that are characteristic of cryobiology—i.e., aqueous solutions potentially containing an extremely wide range of solutes—and, ideally, they should be able to do so without requiring an overwhelming number of experimentally-obtained characteristic coefficients or fitting parameters. One recently-developed solution theory which meets these requirements, and which has been demonstrated to provide accurate predictions of solution behaviour in cryobiologically-relevant solutions, is the Elliott et al. form of the multi-solute osmotic virial equation. However, this solution theory was not yet complete, with some key pieces requiring further work. Accordingly, the overall objective of this thesis was to further develop the Elliott et al. model and to incorporate it into models of cellular osmotic response in order to advance understanding of cell behaviour during cryopreservation.  The work contained in this thesis presents a complete and thermodynamically consistent molality-based form of the Elliott et al. model, capable of modeling all of the solution behaviour required by higher-level cryopreservation models in the complex, non-ideal, multi-solute solutions that occur during cryopreservation. The work herein also conclusively shows that with this solution theory, a grouped intracellular solute approach can be used to represent the cytoplasm without affecting model predictions; thus, this model can be used to provide accurate predictions of non-ideal solution behaviour inside of cells even where—as is generally the case—the composition of the cytoplasm is unknown. Finally, this thesis describes methods for obtaining all of the thermodynamic coefficients required to use the molality-based form of the Elliott et al. model, including those corresponding to a grouped intracellular solute, and provides values of these coefficients for several cryobiologically-relevant solutes and for the grouped intracellular solute of human umbilical vein endothelial cells (HUVECs).    Overall, this thesis advances our understanding of the solution thermodynamics of cryobiology, and—in particular—cellular cryobiology, allowing for more accurate predictions of cryobiological solution behaviour. These advancements will in turn enable greater accuracy in the prediction of cryopreservation processes, thus ultimately aiding in the development of successful cryopreservation protocols.
    

  • Subjects / Keywords
  • Graduation date
    Spring 2019
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-5cx0-v923
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.