Quantitative characterization of cell synchronization in yeast

Abstract

Metabolic oscillations in baker's yeast serve as a model system for synchronization of biochemical oscillations. Despite widespread interest, the complexity of the phenomenon has been an obstacle for a quantitative understanding of the cell synchronization process. In particular, when two yeast cell populations oscillating 180°out of phase are mixed, it appears as if the synchronization dynamics is too fast to be explained. We have probed the synchronization dynamics by forcing experiments in an open-flow reactor, and we find that acetaldehyde has a very strong synchronization effect that can account quantitatively for the classical mixing experiment. The fast synchronization dynamics is explained by a general synchronization mechanism, which is dominated by a fast amplitude response as opposed to the expected slow phase change. We also show that glucose can mediate this kind of synchronization, provided that the glucose transporter is not saturated. This makes the phenomenon potentially relevant for a broad range of cell types. . A manifest demonstration of this phenomenon occurs when two suspensions oscillating 180°out of phase are mixed. Just after mixing, the macroscopic oscillations disappear momentarily, but the two subpopulations synchronize within 5 min (i.e., Ͻ10 times the period of the oscillations) and the macroscopic oscillations reappear with full amplitude (3-5). This indicates active in-phase synchronization. It is believed that the synchronization is mediated by simple metabolites related to glycolysis (1,4,5), and as such it is an example of cell-cell communication that does not depend on any highly specialized signaling molecules or receptors. A similar synchronization mechanism could be operative in any oscillatory cell type, possibly through other metabolic signaling channels. Therefore, the understanding of the mechanism for glycolytic cell synchronization in yeast is important for the general understanding of cellular dynamics and interactions. Acetaldehyde (Aca) has been proposed as mediator of the synchronization (5). If this is the true mechanism of the phenomenon, then this understanding should allow us to explain it not only qualitatively but also quantitatively correct. It has been questioned whether the amount of Aca produced by the yeast cells is enough to cause synchronization (1), and several attempts have been made to account quantitatively for the synchronization process by using mathematical models based on biochemical descriptions (6-8). None of these have, however, been successful in explaining all experimental facts. In all cases, the synchronization process is one order of magnitude too slow, and in some cases the models even predict out-of-phase synchronization instead of the inphase synchronization seen experimentally.A necessary condition for a chemical species to act as a synchronizer is that it can penetrate the cell membrane, and that an instantaneous change in its concentration will influence the oscillations and give rise to an amplitude or phase change. Many differ...

Real-time electrical measurement of L929 cellular spontaneous and synchronous oscillation

“…Oscillations in yeast cells, 1 amoebae Dictyostelium discoideum 2 and pancreatic islets 3 were studied for their regulatory action. Furthermore, spontaneous Ca 2+ oscillation regulates neuronal cell growth, axon outgrowth, and differentiation.…”

Glycolytic Synchronization in Yeast Cells via ATP and Other Metabolites: Mathematical Analyses by Two-Dimensional Reaction-Diffusion Models

“…Various experiments demonstrated that acetaldehyde had a very strong synchronization effect on a suspension of yeast cells [8]. However, these studies do not exclude the possibility that extracellular nucleotides such as ATP and ADP can play an important role in synchronization of glycolytic oscillations in yeast cells.…”

“…It is well known that glycolytic oscillations initiate synchronization under the densely populated condition [3]- [8]. Considering that high population densities mean intense coupling between cells, it is thought that collective properties of synchronization in glycolytic oscillations is triggered by the increase in such parameters as the diffusion coefficient d F , the volumetric ratio of the cell to the compartment φ, the kinetic constant relating to the permeability κ, and so on.…”

“…In this chemical process, synchronized variations can be seen for the concentrations of various metabolites [3]- [8]. For example, yeast cells exhibit glycolytic synchronized oscillations under certain conditions.…”

Topological Determinants of Synchronizability of Oscillators on Large Complex Networks

“…The synchronization of glycolytic oscillation within a cell population is believed to be related to the cell-cell communication with acetaldehyde (Aca) [17][18][19]. Respiratory oscillation may be, suggested by some experiments, closely related to the hydrogen sulfide mediation within the population [5,7,8].…”