AUTHOR=Rowland Adams Joe , Stefanovska Aneta 

TITLE=Modeling Cell Energy Metabolism as Weighted Networks of Non-autonomous Oscillators

JOURNAL=Frontiers in Physiology

VOLUME=Volume 11 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.613183

DOI=10.3389/fphys.2020.613183

ISSN=1664-042X

ABSTRACT=Networks of oscillating processes are a common occurrence in living systems. This is as true as anywhere in the energy metabolism of individual cells. Exchanges of molecules and common regulation operate throughout the metabolic processes of glycolysis and oxidative phosphorylation, making the consideration of each of these as a network a natural step. Oscillations are similarly ubiquitous within these processes, and the frequencies of these oscillations are never truly constant. These features make this system an ideal example with which to discuss an alternative approach to modelling living systems, which focuses on their thermodynamically open, oscillating, nonlinear and nonautonomous nature. We implement this approach in developing a model of nonautonomous Kuramoto oscillators in two all-to-all weighted networks coupled to one another, and themselves driven by nonautonomous oscillators. Each component represents a metabolic process, the networks acting as the glycolytic and oxidative phosphorylative processes, and the drivers as glucose and oxygen supply. We analyse the effect of these features on the synchronisation dynamics within the model, and present a comparison between this model, experimental data on the glycolysis of HeLa cells, and a comparatively mainstream model of this experiment. In the former, we find that the introduction of oscillator networks significantly increases the proportion of the model's parameter space that features some form of synchronisation, indicating a greater ability of the processes to resist external perturbations, a crucial behaviour in biological settings. For the latter, we analyse the oscillations of the experiment, finding a characteristic frequency of 0.1--0.2Hz. We further demonstrate that an output of the model comparable to the measurements of the experiment oscillates in a manner similar to the measured data, achieving this with fewer parameters and greater flexibility than the comparable model.