First Advisor

Mark Woods

Term of Graduation

Spring 2021

Date of Publication

5-14-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.) in Chemistry

Department

Chemistry

Language

English

Subjects

Saccharomyces cerevisiae, Cell membranes, Magnetic resonance imaging, Contrast media (Diagnostic imaging)

DOI

10.15760/etd.7563

Physical Description

1 online resource (xvi, 133 pages)

Abstract

Cellular water exchange is often considered in terms of a change in volume, where a net flux of water moves across the cell membrane due to a change in osmotic pressure. Osmotic pressure can cause a cell to shrink or swell, however, rapid water exchange persists across the membrane even when the volume of the cell is constant. Steady-state transmembrane water exchange describes the exchange of water across the cell membranes which results in no net change in cell volume. This exchange is astonishingly rapid; the entire pool of intracellular water of a Saccharomyces cerevisiae cell may exchange 2-5 times per second. Steady-state water exchange can occur through two major routes. The first of these routes is through passive, osmotically driven processes. Passive water exchange occurs through simple diffusion through the membrane and facilitated diffusion through aquaporin water channels. The second route of steady-state water exchange is through energetically driven active processes. Water chaperones many ions and molecules as they cross the membrane in energetically associated processes. "Active water cycling" was coined by Springer and coworkers to describe the potential for these energetically driven processes to provide diagnostically useful information in an MRI scan. MRI measurements of water exchange has been demonstrated to relate to the activity of ATP driven ion pumps located in the membrane specifically, the Na+/K+ ATPase in mammalian cells and the H+ATPase in yeast cells. The dynamics of the relationships between growth, glucose metabolism and steady state water exchange regulation are still poorly understood. In this work, Saccharomyces cerevisiae was used as a model organism to study water exchange kinetics in contexts that are metabolically relevant as well as potentially diagnostically significant. Using a combination of batch cultures, continuous culture systems, and the Yeast Knockout Library, we explore the effects of cell growth, glucose metabolism and the expression of various membrane transporter genes on the rate constant for steady-state water exchange. In addition, we also demonstrate how commercially available baking yeast can be used as a reliable to model a change in water exchange rate. Using this model, we show how water exchange rates can affect the observed relaxivity of two MRI contrast agents.

Rights

© 2021 Joseph O’Malley Armstrong

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/ This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).

Persistent Identifier

https://archives.pdx.edu/ds/psu/35918

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