Bistability: Requirements on Cell-Volume, Protein Diffusion, and Thermodynamics

TL;DR

This paper investigates the conditions necessary for bistability in biological systems, highlighting the importance of cell volume, protein diffusion, and thermodynamics, and showing its fragility in larger volumes.

Contribution

It maps biological bistable systems onto the Schloegl model, revealing the critical roles of cell volume and diffusion in bistability.

Findings

Bistability requires small cell volumes and fast protein diffusion.

Bistability is fragile and limited to small bacteria and nuclei.

Large volumes tend to lose bistability, leading to phase transitions.

Abstract

Bistability is considered wide-spread among bacteria and eukaryotic cells, useful e.g. for enzyme induction, bet hedging, and epigenetic switching. However, this phenomenon has mostly been described with deterministic dynamic or well-mixed stochastic models. Here, we map known biological bistable systems onto the well-characterized biochemical Schloegl model, using analytical calculations and stochastic spatio-temporal simulations. In addition to network architecture and strong thermodynamic driving away from equilibrium, we show that bistability requires fine-tuning towards small cell volumes (or compartments) and fast protein diffusion (well mixing). Bistability is thus fragile and hence may be restricted to small bacteria and eukaryotic nuclei, with switching triggered by volume changes during the cell cycle. For large volumes, single cells generally loose their ability for bistable switching and instead undergo a first-order phase transition.