An Adder Behavior in Mammalian Cells Achieves Size Control by Modulation of Growth Rate and Cell Cycle Duration

Despite decades of research, it remains unclear how mammalian cell growth varies with cell size and across the cell division cycle to maintain size control. Answers to this question have been limited by the difficulty of directly measuring growth at the single cell level. Here, using a variety of cultured mammalian cell lines, we report direct measurement of single cell volumes over a complete cell division cycle. We show that the volume added across the cell cycle is independent of cell birth size, a size homeostasis behavior called adder. We propose a mathematical framework that can be used to characterize the full spectrum of size homeostasis mechanisms from bacteria to mammalian cells. This reveals that a near-adder is the most common type of size regulation, but shows that it can arise from various types of coupling between cell size, cell growth rate and cell cycle progression.