The dynamics of intracellular water constrains glycolytic oscillations in Saccharomyces cerevisiae

We explored the dynamic coupling of intracellular water with metabolism in yeast cells. Using the polarity-sensitive probe 6-acetyl-2-dimethylaminonaphthalene (ACDAN), we show that glycolytic oscillations in the yeast S. cerevisiae BY4743 wild-type strain are coupled to the generalized polarization (GP) function of ACDAN, which measures the physical state of intracellular water. We analysed the oscillatory dynamics in wild type and 24 mutant strains with mutations in many different enzymes and proteins. Using fluorescence spectroscopy, we measured the amplitude and frequency of the metabolic oscillations and ACDAN GP in the resting state of all 25 strains. The results showed that there is a lower and an upper threshold of ACDAN GP, beyond which oscillations do not occur. This critical GP range is also phenomenologically linked to the occurrence of oscillations when cells are grown at different temperatures. Furthermore, the link between glycolytic oscillations and the ACDAN GP value also holds when ATP synthesis or the integrity of the cell cytoskeleton is perturbed. Our results represent the first demonstration that the dynamic behaviour of a metabolic process can be regulated by a cell-wide physical property: the dynamic state of intracellular water, which represents an emergent property.