A Nonlinear Delay Model for Metabolic Oscillations in Yeast Cells.

ABSTRACT

We introduce two time-delay models of metabolic oscillations in yeast cells. Our model tests a hypothesis that the oscillations occur as multiple pathways share a limited resource which we equate to the number of available ribosomes. We initially explore a single-protein model with a constraint equation governing the total resource available to the cell. The model is then extended to include three proteins that share a resource pool. Three approaches are considered at constant delay to numerically detect oscillations. First, we use a spectral element method to approximate the system as a discrete map and evaluate the stability of the linearized system about its equilibria by examining its eigenvalues. For the second method, we plot amplitudes of the simulation trajectories in 2D projections of the parameter space. We use a history function that is consistent with published experimental results to obtain metabolic oscillations. Finally, the spectral element method is used to convert the system to a boundary value problem whose solutions correspond to approximate periodic solutions of the system. Our results show that certain combinations of total resource available and the time delay, lead to oscillations. We observe that an oscillation region in the parameter space is between regions admitting steady states that correspond to zero and constant production. Similar behavior is found with the three-protein model where all proteins require the same production time. However, a shift in the protein production rates peaks occurs for low available resource suggesting that our model captures the shared resource pool dynamics.