Zandieh, A. | Search bioRxiv

bioRxiv2025

A Dynamic Model of Calcium Frequency Modulation by Mitochondrial Superoxide

Numerous studies have highlighted the crucial roles of cytosolic calcium transients mediated by inositol 1,4,5-trisphosphate receptor (IP3R) channels in intracellular signaling, as well as the significant modulatory effects of cytosolic redox state on these dynamics. Accordingly, developing a mathematical model that captures the core dynamics by which redox state of IP3Rs influence calcium signaling would provide a valuable foundation for simulating and predicting experimental observations. In this study, we developed a dynamic system, based on ordinary differential equations that incorporates a kinetic model for the redox dynamic of the IP3R and the role of this dynamic on the channels gating parameters. Using this framework, we simulated both the static and dynamic effects of mitochondria-derived superoxide fluctuations on local calcium oscillations in non-excitable cells. Numerical solutions demonstrated that the model quantitatively reproduced experimentally observed changes in local calcium oscillation frequency in response to mitochondria-derived superoxide variations. Overall, the proposed model offers a predictive tool for exploring how redox perturbations in non-excitable cells affect cellular signaling pathways through calcium frequency modulation.

cell biology↗

bioRxiv2024

An Amplification Mechanism for Weak ELF Magnetic Fields Quantum-Bio Effects in Cancer Cells

Observing quantum mechanical characteristics in biological processes is a surprising and important discovery. One example, which is gaining more experimental evidence and practical applications, is the effect of weak magnetic fields with extremely low frequencies on cells, especially cancerous ones. In this study, we use a mathematical model of ROS dynamics in cancer cells to show how ROS oscillatory patterns can act as a resonator to amplify the small effects of the magnetic fields on the radical pair dynamics in mitochondrial Complex III. We suggest such a resonator can act in two modes for distinct states in cancer cells: 1) cells at the edge of mitochondrial oscillation and 2) cells with local oscillatory patches. When exposed to magnetic fields, the first group exhibits high-amplitude oscillations, while the second group synchronizes to reach a whole-cell oscillation. Both types of amplification are frequency-dependent in the range of hertz and sub-hertz. We use UV radiation as a positive control to observe the two states of cells in DU and HELA cell lines. Application of magnetic fields shows frequency-dependent results on both the ROS and mitochondrial potential which agree with the model for both type of cells. We also observe the oscillatory behavior in the time-lapse fluorescence microscopy for 0.02 Hz magnetic fields. Finally, we investigate the dependence of the results on the field strength and propose a quantum spin-forbidden mechanism for the effect of magnetic fields on superoxide production in QO site of mitochondrial Complex III.

biophysics↗