Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

A minimal “push-pull” bistability model explains oscillations between quiescent and proliferative cell states.

Publication Type

Journal Article

Date of Publication

September 15, 2018

Journal

Molecular biology of the cell

Volume/Issue

29/19

ISSN

1939-4586

A minimal model for oscillating between quiescent and growth/proliferation states, dependent on the availability of a central metabolic resource, is presented. From the yeast metabolic cycles, metabolic oscillations in oxygen consumption are represented as transitions between quiescent and growth states. We consider metabolic resource availability, growth rates, and switching rates (between states) to model a relaxation oscillator explaining transitions between these states. This frustrated bistability model reveals a required communication between the metabolic resource that determines oscillations and the quiescent and growth state cells. Cells in each state reflect memory, or hysteresis of their current state, and “push-pull” cells from the other state. Finally, a parsimonious argument is made for a specific central metabolite as the controller of switching between quiescence and growth states. We discuss how an oscillator built around the availability of such a metabolic resource is sufficient to generally regulate oscillations between growth and quiescence through committed transitions.

Alternate Journal

Mol Biol Cell

PubMed ID

30044724

PubMed Central ID

PMC6249812

Authors

Sandeep Krishna
Sunil Laxman

Keywords

Cell Cycle
NADP
Acetyl Coenzyme A
Models, Biological
Cell Proliferation
Saccharomyces cerevisiae
Oxygen