Beyond Phantom Baths: Balanced Physical Fidelity for Responsive Virtual Cells

A genuinely responsive virtual cell must capture the nonequilibrium dynamics of living systems, not merely infer cellular states through statistical projection. This in turn requires balanced physical fidelity between the representation of interior dynamics and environmental coupling. Standard thermostats and barostats are phantom baths: algorithmic reservoirs that impose instantaneous, global control in place of physically mediated exchange. They thereby distort broad classes of cellular processes that depend on localized transport of heat, momentum, and matter. As path-integral methods, AI force fields, and quantum computing push interior fidelity to progressively higher levels of accuracy, this imbalance becomes increasingly consequential. To clarify what is at stake across the full range of virtual-cell approaches, this perspective introduces the physical-fidelity continuum, spanning predictive-statistical models, mechanistic dynamical simulations, and the physical-accuracy limit set by quantum-computational approximations and available experimental validation. A focus-dynamic hybrid architecture and benchmark hierarchy are proposed as the constructive framework for achieving and verifying balanced physical fidelity.