Glycolytic Oscillation & Synchronization

Simplified glycolytic pathway

Experimental observation 1glycolytic oscillation

• A population of starved yeasts will obtain synchronized glycolytic oscillation after putting glucose and cyanide into the suspension

• Oscillating period 40s (cell cycle 80~100 min) ( if I am the yeast, then oscillating period be like how often I take the final exam)

Experimental observation 2glycolytic synchronization

• 2 populations of yeasts with 180 degree out of phase will re-synchronize after mixing

• Re-synchronizing time after mixing

about 6 min (i.e. 9 periods of oscillation)

• The amplitude and frequency will maintain the same after the synchronization

Experimental observation

Two suspensions of yeast cells that oscillate with equal amplitude and opposite phase are mixed. We again observe that macroscopic oscillations develop and that the amplitude increases until a limit is reached asymptotically. This behavior is indicative of limit cycle dynamics.

Experimental observation

Experiment Conditionwhy cyanide?

• block respiration • trap acetaldehyde (this compound is found to be the key of

synchronization)

Discussionwhy oscillate?

• Regulation of PFK

PFK INHIBITOR atp

Discussionwhy synchronize?

• Possible candidates for synchronizer must have the following properties:

1.can penetrate the cell membrane; 2.oscillates in the extracellular medium as a

result of periodic excretion or absorption by the cells

• Possible candidates: temperature, glucose, Aca

Possible candidates temperature lose the campaign

• Temperature oscillation due to glycolytic oscillation is 1–2 mK (this is observed in experiments, but simple calculation gives about the same result)

• Observed temperature amplitude can only give rise to a frequency change of 0.2‰

Possible candidates glucose

Possible candidatesAca

Aca forcing experiment

Aca forcing experiment

• the distance from the center indicates the NADH amplitude a relative to the fully entrained NADH amplitude a entrained, and the angle indicates the phase difference between the forcing and the NADH signal

Modeling

Modeling

denotes the ratio of the total cellular volume, VC=nV, to theextracellular volume, VE.

Modeling

The parameter values of that reference state have been selected in such a way that the metabolite concentrations are in a realistic range for yeast cells

Simulation Results (for 1000 cells)

intracellular concentrations of each cell are randomly perturbed from nominal values that produce synchronous oscillations

Simulation Results (mixing 2 sub-populations)

The middle plot shows the average intracellular NADH concentration dynamics and the bottom plot shows computed cell number distributions at 0 min (—), 11.25 min (· · ·), 30 min (– – –) and 45 min (– · – ·)

Small density of yeast cells

Amplitude dies out as desity decreases

Small density of yeast cells

Remarks on the model

• The model can give the trend of oscillation

• However, the amplitude of the oscillation is too large compared to experiments

• The re-synchronizing time is 2~3 times longer than the experimental results

• For small density of yeast cells, the model may not fit

Thank you!