Theoretical basis for cell deaths

Understanding deaths and life-death boundaries of cells is a fundamental challenge in biological sciences. In this study, we present a theoretical framework for investigating cell death. We conceptualize cell death as a controllability problem within dynamical systems, and compute the life-death boundary through the development of “stoichiometric rays.” This method utilizes enzyme activity as control parameters, exploiting the inherent property of enzymes to enhance reaction rates without affecting thermodynamic potentials. This approach facilitates the efficient evaluation of the global controllability of models. We demonstrate the utility of our framework using its application to a toy metabolic model, where we delineate the life-death boundary. The formulation of cell death through mathematical principles provides a foundation for the theoretical study of cellular mortality. Published by the American Physical Society 2024