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

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.Comment: 23 pages, 8 figure

Entropy production selects nonequilibrium states in multistable systems

Far-from-equilibrium thermodynamics underpins the emergence of life, but how has been a long-outstanding puzzle. Best candidate theories based on the maximum entropy production principle could not be unequivocally proven, in part due to complicated physics, unintuitive stochastic thermodynamics, and the existence of alternative theories such as the minimum entropy production principle. Here, we use a simple, analytically solvable, one-dimensional bistable chemical system to demonstrate the validity of the maximum entropy production principle. To generalize to multistable stochastic system, we use the stochastic least-action principle to derive the entropy production and its role in the stability of nonequilibrium steady states. This shows that in a multistable system, all else being equal, the steady state with the highest entropy production is favored, with a number of implications for the evolution of biological, physical, and geological systems.Comment: 15 pages, 4 figure

Noise characteristics of the Escherichia coli rotary motor

The chemotaxis pathway in the bacterium Escherichia coli allows cells to detect changes in external ligand concentration (e.g. nutrients). The pathway regulates the flagellated rotary motors and hence the cells' swimming behaviour, steering them towards more favourable environments. While the molecular components are well characterised, the motor behaviour measured by tethered cell experiments has been difficult to interpret. Here, we study the effects of sensing and signalling noise on the motor behaviour. Specifically, we consider fluctuations stemming from ligand concentration, receptor switching between their signalling states, adaptation, modification of proteins by phosphorylation, and motor switching between its two rotational states. We develop a model which includes all signalling steps in the pathway, and discuss a simplified version, which captures the essential features of the full model. We find that the noise characteristics of the motor contain signatures from all these processes, albeit with varying magnitudes. This allows us to address how cell-to-cell variation affects motor behaviour and the question of optimal pathway design. A similar comprehensive analysis can be applied to other two-component signalling pathways.Comment: 22 pages, 7 figures, 3 tutorials, supplementary information; submitted manuscrip