AUTHOR=Rowland Adams Joe , Stefanovska Aneta TITLE=Modeling Cell Energy Metabolism as Weighted Networks of Non-autonomous Oscillators JOURNAL=Frontiers in Physiology VOLUME=11 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 modeling living systems, which focuses on their thermodynamically open, oscillating, non-linear and non-autonomous nature. We implement this approach in developing a model of non-autonomous Kuramoto oscillators in two all-to-all weighted networks coupled to one another, and themselves driven by non-autonomous 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 synchronization 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 synchronization, indicating a greater ability of the processes to resist external perturbations, a crucial behavior in biological settings. For the latter, we analyse the oscillations of the experiment, finding a characteristic frequency of 0.01–0.02 Hz. 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.