The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation

Abstract

Budding yeast cells are assumed to trigger Start and enter the cell cycle only after they attain a critical size set by external conditions. However, arguing against deterministic models of cell size control, cell volume at Start displays great individual variability even under constant conditions. Here we show that cell size at Start is robustly set at a single-cell level by the volume growth rate in G1, which explains the observed variability. We find that this growth-rate-dependent sizer is intimately hardwired into the Start network and the Ydj1 chaperone is key for setting cell size as a function of the individual growth rate. Mathematical modelling and experimental data indicate that a growth-rate-dependent sizer is sufficient to ensure size homeostasis and, as a remarkable advantage over a rigid sizer mechanism, it reduces noise in G1 length and provides an immediate solution for size adaptation to external conditions at a population level.

We thank A. Cornadó and S. Rius for technical assistance, J.C. Igual for communicating unpublished results and R. Y. Tsien for the mCherry fusion vector. We also thank A. Aubanell, T. Mazza and J. Sánchez-Matamala for key preliminary contributions, and B. Novak, P. Nurse and J. Torres-Rosell for stimulating discussions. This work was funded by the Ministry of Science and Innovation of Spain (BFU2010-20205), Consolider-Ingenio 2010 (CSD2007-15), the Italian Research Fund FIRB (RBPR0523C3) and the European Union (FEDER). F.F. and N.C. are researchers of the Ramón y Cajal programme.