From deterministic to fuzzy decision-making in artificial cells

Ferdinand Greiss,Roy Bar-Ziv,Vincent Noireaux,Shirley S Daube

doi:10.1038/s41467-020-19395-4

Ferdinand Greiss, Roy Bar-Ziv + Show 2 more

Open Access

https://doi.org/10.1038/s41467-020-19395-4

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Abstract

Building autonomous artificial cells capable of homeostasis requires regulatory networks to gather information and make decisions that take time and cost energy. Decisions based on few molecules may be inaccurate but are cheap and fast. Realizing decision-making with a few molecules in artificial cells has remained a challenge. Here, we show decision-making by a bistable gene network in artificial cells with constant protein turnover. Reducing the number of gene copies from 105 to about 10 per cell revealed a transition from deterministic and slow decision-making to a fuzzy and rapid regime dominated by small-number fluctuations. Gene regulation was observed at lower DNA and protein concentrations than necessary in equilibrium, suggesting rate enhancement by co-expressional localization. The high-copy regime was characterized by a sharp transition and hysteresis, whereas the low-copy limit showed strong fluctuations, state switching, and cellular individuality across the decision-making point. Our results demonstrate information processing with low-power consumption inside artificial cells.

Highlights

Building autonomous artificial cells capable of homeostasis requires regulatory networks to gather information and make decisions that take time and cost energy
We demonstrate that gene regulation in artificial cells appears at lower concentrations than necessary for the equilibrium binding of transcription factor to its target sites, and that the decision-making of the genetic regulatory network (GRN) trades speed with accuracy through the transition from low to high gene densities
We suggest co-expressional localization to enhance binding rates (Fig. 3)[34], a nonequilibrium mechanism that seems to be essential for realizing gene regulation with a few molecules in our artificial cells

Summary

Introduction

Building autonomous artificial cells capable of homeostasis requires regulatory networks to gather information and make decisions that take time and cost energy. Reducing the number of gene copies from 105 to about 10 per cell revealed a transition from deterministic and slow decision-making to a fuzzy and rapid regime dominated by small-number fluctuations. Decision-making of a genetic regulatory network (GRN) should be precise and deterministic when the process is averaged over many molecules. In the small-number limit, fluctuations in gene expression with a few molecules, little averaging, may reduce the precision and lead to fuzzy decision-making dominated by fluctuations (Fig. 1a, b). We demonstrate that gene regulation in artificial cells appears at lower concentrations than necessary for the equilibrium binding of transcription factor to its target sites, and that the decision-making of the GRN trades speed with accuracy through the transition from low to high gene densities

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