Multigenerational memory in cell size homeostasis

Cells need to maintain a stable size as they grow and divide to survive. Most experiments suggest that fluctuations around the stable size last for only a generation or two. However, recent evidence suggests that after controlling for environmental effects, fluctuations can persist for many generations. Here we develop a minimal model that takes into account the competition between environmental effects and phenotypic inheritance to explain these results. Our model suggests that the role of the environment is to set the homeostasis parameters over long timescales; different environments have different parameters. Thus, multigenerational memory is revealed in constant environments but obscured when averaging over many different environments. Inferring the parameters of our model from cell size data in microfluidic experiments, we recapitulate the observed statistics of homeostasis and phenotypic inheritance. Our work provides new insights into the impact of the environment on cell homeostasis.