Presentation Type

Oral Presentation

Start Date

5-8-2024 1:00 PM

End Date

5-8-2024 3:00 PM

Subjects

Mitochondria, Cell membranes

Advisor

Mark Woods

Student Level

Doctoral

Abstract

Water transport across the lipid bilayer due to osmotic stress causes a change in intracellular volume over time. At isotonic equilibrium there is no change in cell volume and yet water exchange does not stop. Water molecules continue to exchange rapidly with those of the extracellular space. The rate constant for steady state water efflux (kio) can be measured using contrast enhanced magnetic resonance (MR) and the two-site exchange (2SX) model. kio is known to correlate with the cellular energy molecule ATP making it a probable biomarker for metabolic diseases such as cancer. Measurements of kio across tumors show areas of heterogeneity, making it a promising diagnostic tool for personalized medicine. However, in vivo studies are restricted to imaging voxel size. A voxel can contain up to 100,000 cells. Thus, a simple homogenous model is needed for characterization of water exchange. S. cerevisiae (yeast) provides an excellent platform for studying kio. Yeast cells were grown in parallel, in respiring and fermenting metabolic regimes in chemostat bioreactors. The effect of mitochondrial activity was investigated in yeast though the use of metabolic modulators, such as 2,4-dinitrophenol (2,4-DNP). When fermenting cells were exposed to 2,4-DNP a biphasic response was observed in ATP. This response was also reflected the measured values of kio. These findings suggest that mitochondrial activity may be a driving factor in water exchange at the cell membrane (kio).

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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May 8th, 1:00 PM May 8th, 3:00 PM

The Effect Of Metabolic Modulators On The Rate Of Steady State Water Exchange In S. Cerevisiae Grown In Chemostat Bioreactors

Water transport across the lipid bilayer due to osmotic stress causes a change in intracellular volume over time. At isotonic equilibrium there is no change in cell volume and yet water exchange does not stop. Water molecules continue to exchange rapidly with those of the extracellular space. The rate constant for steady state water efflux (kio) can be measured using contrast enhanced magnetic resonance (MR) and the two-site exchange (2SX) model. kio is known to correlate with the cellular energy molecule ATP making it a probable biomarker for metabolic diseases such as cancer. Measurements of kio across tumors show areas of heterogeneity, making it a promising diagnostic tool for personalized medicine. However, in vivo studies are restricted to imaging voxel size. A voxel can contain up to 100,000 cells. Thus, a simple homogenous model is needed for characterization of water exchange. S. cerevisiae (yeast) provides an excellent platform for studying kio. Yeast cells were grown in parallel, in respiring and fermenting metabolic regimes in chemostat bioreactors. The effect of mitochondrial activity was investigated in yeast though the use of metabolic modulators, such as 2,4-dinitrophenol (2,4-DNP). When fermenting cells were exposed to 2,4-DNP a biphasic response was observed in ATP. This response was also reflected the measured values of kio. These findings suggest that mitochondrial activity may be a driving factor in water exchange at the cell membrane (kio).