Start & Stop: a PhysiCell and PhysiBoSS 2.0 add-on for interactive simulation control

In computational biology, in silico simulators are vital for exploring and understanding the behavior of complex biological systems. Hybrid multi-level simulators, such as PhysiCell and PhysiBoSS 2.0, integrate multiple layers of biological complexity, providing deeper insights into emergent patterns. However, one key limitation of these simulators is the inability to adjust simulation parameters once the simulation has started, which hinders the interactive exploration and adaptation of dynamic protocols ranging from biofabrication to in vitro pharmacological testing. To address this challenge, we introduce the Start & Stop add-on for PhysiCell and PhysiBoSS 2.0. This add-on offers multi-level state preservation and multi-modal stop control, triggered by simulation time or cell conditions, enabling users to pause a simulation, adjust parameters, and then resume from the exact halted state. We validate Start & Stop using two well-established PhysiBoSS 2.0 use cases, a tumor spheroid 3T3 mouse fibroblasts use case under tumor necrosis factor (TNF) stimulation, and a lung cancer cell line invasion simulation, demonstrating that it preserves the simulator's original behavior while enabling interactive configuration changes that facilitate the exploration of diverse and adaptive treatment strategies. By enhancing flexibility and user interaction, Start & Stop makes PhysiCell and PhysiBoSS 2.0 more akin to real in vitro scenarios, thus expanding the range of potential simulations and advancing more effective protocol development in a variety of applications.