Realistic image-based simulations of multicellular systems exposed to electric fields for applications in impedance sensing and electrical stimulation

Advanced microscopy techniques enable live imaging of biological processes in multicellular systems with subcellular resolution. New insights into tissue–electric field interactions are unlocked by combining microscopy with microelectrodes for impedance analysis and electrical stimulation. However, a streamlined pipeline to develop realistic numerical simulations for electric field computations from imaging data is currently lacking. We present a user-friendly, automated, and efficient solution to bridge this gap. The method relies on well-established open-source software and can be readily deployed on a high-performance computing cluster. Verification cases with known analytical solutions demonstrate the high accuracy and reliability of the method. As demonstration cases of application scenarios of our method, we show how the electric field exposure of multicellular geometries imaged by 3D fluorescence microscopy can be numerically computed. Moreover, impedance spectra and the local effect of electrical stimulation by microelectrodes are computed. Finally, sensitivities to cell state and morphology are outlined, providing a basis for the rational design of future experiments. • Simulating electric fields in 3D multicellular systems with flexible electrodes. • Pipeline converts 3D microscopy masks into meshes for finite-element simulation. • Simulations predict impedance and local responses at the cellular scale. • Biological details from microscopy images are directly integrated. • Workflow supports sample-specific biosensor analysis and design.