A Theoretical Model for the Cell Cycle and Drug Induced Cell Cycle Arrest of FUCCI Systems with Cell-to-Cell Variation during Mitosis

PurposeSince the molecular mechanism of the cell cycle was established, various theoretical models of this process have been developed. A recent study revealed significant variability in cell cycle duration between mother and daughter cells, but this observation has not been incorporated into the theoretical models.MethodsWe used fluorescent ubiquitination-based cell cycle indicator (FUCCI) systems and live-monitored the heterogeneity of cell cycle progression within daughter cells, which accounts for dephasing synchrony. To incorporate the variable cell cycle durations into a model, we modified a two-ordinary differential equation (ODE) model based on reciprocal activation between CDK1 and APC.ResultsOur model reproduced the experimental population profile, in which cell cycle synchrony dephased due to variability. Based on this model, we determined parameters for CDK1 and APC in the cell cycle profile after treatment with antimitotic drugs and associated the parameters with the drugs' mode of action as cell cycle inhibitors.ConclusionThis suggests that this model is useful for determining the mode of action of unknown small molecules on the cell cycle.