Proliferating cells must adjust their division time with the rate by which they accumulate biomass, as growing too much, or too little during the cell division will result in the loss of growth homeostasis. Size control mechanisms provide an internal coupling of growth and division by modulating the division cycle based on cell size. Using the budding yeast as a model system, I will discuss cell-cycle data from thousands of individual growing cells, which challenges existing size-control (checkpoint-based) paradigms. I will further describe genetic manipulations that decouple cell division from cell size, leading to the loss of growth homeostasis, with cells becoming progressively smaller or progressively larger until arresting. Based on this data, I will argue that coordination of size and division observed in wild-type cells reflects tuning of two parallel processes, which is only refined by an inherent feedback-dependent coupling. Finally, I will present a class of size control models that is consistent with our single-cell data and explains the observed breakdown of growth homeostasis.
