Coordination of cell growth and cell division: a mathematical modeling study

Although there is general agreement that cell growth and division are functionally coordinated, the mechanisms that link the two processes are poorly understood. In this study, we have developed a mathematical model based on current biological concepts of the signaling transduction pathways involved in cell growth, which predicts that cell growth rate is proportional to cell surface area at birth. To investigate the relationship between growth control and cell division, we then applied our mathematical model to three classic experiments measuring cycle time versus cell birth size in fission yeast and Xenopus laevis, and the cell cycle delay in mammalian cells after serum withdrawal. When coupled to a cell cycle exhibiting 'sizer' and 'timer' phases, we show that a simple model in which growth rate is proportional to the cell surface area immediately after division reproduces the experimental observations including the relationship between cycle time and birth size in fission yeast and Xenopus laevis. The model also accounts for the cell cycle delay seen in restriction point experiments performed in HeLa cells.