Cytomorphic electronic system design of apoptosis pathway with extrinsic and intrinsic perturbations

Integrating biological phenomena with electronic circuits paves the way for innovative bio-inspired System-on-Chip (SoC) designs. These SoCs capture the stochasticity, non-linearity, and dynamic behavior of complex biological pathways, offering a more economical, faster, and cruelty-free approach to conducting drug trials. We draw analogies between chemistry and subthreshold electronics to create fast, scalable, bio-inspired Metal Oxide Semiconductor (MOS)-based SoC design of stochastic apoptosis networks. Mathematical models for the proteins involved in the apoptosis pathway are developed using nonlinear ordinary differential equations to capture their interdependent dynamics in response to stimuli. The pathway is represented as a system governed by the principles of Michaelis-Menten kinetics and steady-state approximations. This system model is then translated into an equivalent electronic circuit, where each component is implemented using a MOSFET-based dual-stage differential amplifier. The simulation results, depicting the concentrations of pro- and anti-apoptotic proteins, accurately replicate their respective dynamics and inter-molecular interactions throughout the apoptosis process. We have validated our simulated data with cell-culture based-data using Pearson's correlation method for the proteins, showing strong positive correlation. Quantitative analysis using bio-simulator tool COPASI 4.25, shows noteworthy resemblance with simulated outcomes. Additionally, the cytomorphic system satisfies the stability criteria in both continuous and discrete time domains, ensuring its feasibility and reliability.