Unification of aggregate growth models by emergence from cellular and intracellular mechanisms.

Multicellular aggregate growth is regulated by nutrient availability and removal of metabolites, but the specifics of growth dynamics are dependent on cell type and environment. Classical models of growth are based on differential equations. While in some cases these classical models match experimental observations, they can only predict growth of a limited number of cell types and so can only be selectively applied. Currently, no classical model provides a general mathematical representation of growth for any cell type and environment. This discrepancy limits their range of applications, which a general modelling framework can enhance. In this work, a hybrid cellular Potts model is used to explain the discrepancy between classical models as emergent behaviours from the same mathematical system. Intracellular processes are described using probability distributions of local chemical conditions for proliferation and death and simulated. By fitting simulation results to a generalization of the classical models, their emergence is demonstrated. Parameter variations elucidate how aggregate growth may behave like one classical growth model or another. Three classical growth model fits were tested, and emergence of the Gompertz equation was demonstrated. Effects of shape changes are demonstrated, which are significant for final aggregate size and growth rate, and occur stochastically.