title: Size homeostasis can be intrinsic to growing cell populations and explained without size sensing or signalling.
abstract: The cell division cycle orchestrates cellular growth and division. The machinery underpinning the cell division cycle is well characterized, but the actual cue(s) driving the cell division cycle remains unknown. In rapidly growing and dividing yeast cells, this cue has been proposed to be cell size. Presumably, a mechanism communicating cell size acts as gatekeeper for the cell division cycle via the G(1) network, which triggers G(1) exit only when a critical size has been reached. Here, we evaluate this hypothesis with a minimal core model linking metabolism, growth and the cell division cycle. Using this model, we (a) present support for coordinated regulation of G(1)/S and G(2)/M transition in Saccharomyces cerevisiae in response to altered growth conditions, (b) illustrate the intrinsic antagonism between G(1) progression and cell size and (c) provide evidence that the coupling of growth and division is sufficient to allow for size homeostasis without directly communicating or measuring cell size. We show that even with a rudimentary version of the G(1) network consisting of a single unregulated cyclin, size homeostasis is maintained in populations during autocatalytic growth when the geometric constraint on nutrient supply is considered. Taken together, our results support the notion that cell size is a consequence rather than a regulator of growth and division.
authors.affiliation: Theoretical Biophysics, Humboldt-Universität zu Berlin, Germany.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Spiesser
authors.forename: Christiane
authors.initials: C
authors.lastname: Müller
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schreiber
authors.forename: Marcus
authors.initials: M
authors.lastname: Krantz
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D048429:Cell Size; D003198:Computer Simulation; D006706:Homeostasis; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction