Bioelectrical interfaces beyond excitable cells: cancer, aging, and gene expression modulation
The investigation of biological conductivity has evolved from its classical foundation based on ionic fluxes underpinning cardiac and neuronal excitability to a multifaceted regulator of cellular physiology. Traditional approaches for probing electrical events in living matter focused largely on action potentials recording. However, bioelectricity in non-excitable cells governs key phenomena, including developmental patterning, tissue homeostasis, and disease progression. Pioneering studies implicated endogenous bioelectrics in many aspects of morphogenesis, wound healing, regeneration, and cancer. Early findings laid the groundwork for viewing bioelectricity as a means to influence cell fate, cell cycle progression, differentiation, and senescence. More recently, spatial variations in membrane potential within tumor microenvironments were found to correlate with metastatic potential. In parallel, substantial breakthroughs have been achieved in designing advanced bioelectrical interfaces for the study of neuronal networks and cardiac function. This perspective bridges the engineering and biological domains by examining how such technologies might enable new insights into non-excitable cell electrical events at different scales of operation to ultimately manipulate cellular pathways in cancer reprogramming, anti-aging interventions, and gene expression modulation.