Browsing by Author "Sule, Kevin Charles Macam"

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    Effects of manganese on the biophysical and biochemical properties of biologically relevant membranes and yeast
    (2023-04-26) Sule, Kevin Charles Macam; Prenner, Elmar Josef; Zaremberg, Vanina; Fraser, Marie; Heyne, Belinda; Thewalt, Jenifer
    Metal ion-membrane interactions have gained appreciable attention over the years with increasing interest in the mode of action of toxic and essential metals. Lipids are a potential metal binding targets leading to altered lipid-lipid interactions or lateral membrane organization. Despite its essentiality, manganese (Mn2+) stress can induce deleterious impact towards cell survival. The mechanisms by which Mn2+ exert damage at the biomolecular level are not fully understood. Thus, the goal of this thesis was to investigate the effects of the essential trace metal Mn2+ on model lipid systems comprised of zwitterionic and anionic glycerophospholipids, complex biological extracts and yeast (S. cerevisiae). The data shows that Mn2+ was able to rigidify bilayer membranes containing negatively charged lipids, in a dose dependent manner, in both simple and complex model membranes. In simple model membranes, liposome swelling, and extensive aggregation were also detected for some lipids. This documents that on top of electrostatic attraction, the detailed lipid structure in terms or charge location and side chain architecture needs to be considered. Moreover, Mn2+ caused both an expansion and condensation of phosphoinositide containing monolayers, whilst inducing lateral disorganization by abolishing lipid domains. The potential negatively impacting such domains that are essential for a multitude to signalling processes is an important result as well. Mn2+ was able to alter the impact of binary metal mixtures with Ca2+ and Mg2+ on selected liposomes. Metal induced changes in membrane rigidity depended on the details of lipid structure and differed for single metals or binary mixtures. This suggests that the impact of metals will depend on the localized lipid composition and the presence of other ions. Mn2+ was also found to catalyze lipid peroxidation in complex systems via Fenton reaction. Lastly, growth, organelle morphology, and lipid content were disrupted by Mn2+ stress on the model cell S. cerevisiae, suggesting both direct and indirect effects on membrane properties. This thesis contributed to a better understanding of Mn2+ effects on biological membranes and yeast that can be consequential for their proper structural and signalling functions and ultimately cell survival. This work also opens avenues for future research in these areas.