Abstract
Cell signaling, gene expression, and metabolism are affected by cell-cell heterogeneity and random changes in the environment. The effects of such fluctuations on cell signaling and gene expression have recently been studied intensively using single-cell experiments. In metabolism heterogeneity may be particularly important because it may affect synchronisation of metabolic oscillations, an important example of cell-cell communication. This synchronisation is notoriously difficult to describe theoretically as the example of glycolytic oscillations shows: neither is the mechanism of glycolytic synchronisation understood nor the role of cell-cell heterogeneity. To pin down the mechanism and to assess its robustness and universality we have experimentally investigated the entrainment of glycolytic oscillations in individual yeast cells by periodic external perturbations. We find that oscillatory cells synchronise through phase shifts and that the mechanism is insensitive to cell heterogeneity (robustness) and similar for different types of external perturbations (universality).
Highlights
Cell signaling, gene expression, and metabolism are affected by cell-cell heterogeneity and random changes in the environment
We find that oscillatory cells synchronise through phase shifts and that the mechanism is insensitive to cell heterogeneity and similar for different types of external perturbations
Our data show that the strongest phase response is achieved when the concentration of NADH is at a minimum, where the removal of cyanide prolongs the subsequent period roughly by one third
Summary
Gene expression, and metabolism are affected by cell-cell heterogeneity and random changes in the environment. The discrete nature of molecular reactions as well as environmental fluctuations and heterogeneity cause fluctuations in these processes The effect of such noise on cell signaling and gene expression has recently been studied intensively using single-cell analysis[1,2,3,4,5]. Yeast cells in dense populations appear to be able to synchronise their glycolytic oscillations[9,12,13,14,15] and macroscopic oscillations have been observed in yeast populations[7,8,9,10] This effect appears quite universal in that different signaling molecules/receptors can cause synchronisation[9,12,13,14,15,16,17,18,19]. To achieve a qualitative and quantitative understanding of the phenomenon requires us to answer three fundamental questions
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