Sustained oscillations in living cells

Abstract

Glycolytic oscillations in yeast have been studied for many years simply by adding a glucose pulse to a suspension of cells and measuring the resulting transient oscillations of NADH. Here we show, using a suspension of yeast cells, that living cells can be kept in a well defined oscillating state indefinitely when starved cells, glucose and cyanide are pumped into a cuvette with outflow of surplus liquid. Our results show that the transitions between stationary and oscillatory behaviour are uniquely described mathematically by the Hopf bifurcation. This result characterizes the dynamical properties close to the transition point. Our perturbation experiments show that the cells remain strongly coupled very close to the transition. Therefore, the transition takes place in each of the cells and is not a desynchronization phenomenon. With these two observations, a study of the kinetic details of glycolysis, as it actually takes place in a living cell, is possible using experiments designed in the framework of nonlinear dynamics. Acetaldehyde is known to synchronize the oscillations. Our results show that glucose is another messenger substance, as long as the glucose transporter is not saturated.

General Chemotactic Model of Oscillators

“…These reveal the world-wide importance of such studies. In this paper, the elements denote symptoms such as a bacterium having an internal network of genes and proteins (6), a reactive droplet in reaction-diffusion systems(7), a neuron in networks (8,9), etc (10)(11)(12)(13)(14). These elements exhibit not only spatio-temporal patterns but also collective functions.…”

Complex bursting in pancreatic islets: a potential glycolytic mechanism

“…It converts glucose to products that are further processed in the mitochondria to produce adenosine triphosphate (ATP) from adenosine diphosphate (ADP). Oscillations in glycolysis have been observed in yeast (Betz and Chance, 1965;Dan^et al, 1999), muscle extracts Lowenstein, 1974, 1975), and b-cells (Longo et al, 1991). These oscillations are thought to be due to the allosteric enzyme phosphofructokinase (PFK), which phosphorylates fructose-6-phosphate (F6P) to form fructose 1,6-bisphosphate (FBP).…”

Dynamical responses of oscillating yeast cell suspensions to periodic forcing.

“…These methodological advances have paved the way to quantitative modelling of such biological populations, and in particular for oscillations in glycolysis and in genetically engineering circuits [3,7,8,5]. Quantitative approaches have complemented qualitative modelling approaches [2,9] by elucidating how given dynamical features are implemented in a particular biological system.…”

“…The use of bioreactors [3,4,6], and later of microfluidic devices [5], allowed to keep the environmental conditions so stable that a steady dynamical behaviour could be quantitatively characterized. These methodological advances have paved the way to quantitative modelling of such biological populations, and in particular for oscillations in glycolysis and in genetically engineering circuits [3,7,8,5].…”

“…Oscillations that appear at the population level typically involve the cell metabolism [2,3,4]: they stem from regulatory feedbacks in the metabolic pathway and are efficiently coupled by passive diffusion of some metabolites. In some cases, genetic and metabolic changes co-occur, as in the case of ultradian oscillations in 78 DYNAMICAL RESPONSES OF OSCILLATING YEAST CELLS SUSPENSIONS TO PERIODIC FORCING yeast [4].…”