Modeling Bioelectric State Transitions in Glial Cells: An ASAL-Inspired Computational Approach to Glioblastoma Initiation

Understanding how glioblastoma (GBM) emerges from initially healthy glial tissue requires models that integrate bioelectrical, metabolic, and multicellular dynamics. This work introduces an ASAL-inspired agent-based framework that simulates bioelectric state transitions in glial cells as a function of mitochondrial efficiency (Meff), ion-channel conductances, gap-junction coupling, and ROS dynamics. Using a 64x64 multicellular grid over 60,000 simulation steps, we show that reducing Meff below a critical threshold (~0.6) drives sustained depolarization, ATP collapse, and elevated ROS, reproducing key electrophysiological signatures associated with GBM. We further apply evolutionary optimization (genetic algorithms and MAP-Elites) to explore resilience, parameter sensitivity, and the emergence of tumor-like attractors. Early evolutionary runs converge toward depolarized, ROS-dominated regimes characterized by weakened electrical coupling and altered ionic transport. These results highlight mitochondrial dysfunction and disrupted bioelectric signaling as sufficient drivers of malignant-like transitions and provide a computational basis for probing the bioelectrical origins of oncogenesis.