Intracellular Energy Variability Modulates Cellular Decision-Making Capacity

TL;DR

This paper explores how intracellular energy variability influences cellular decision-making capacity, revealing that energy levels modulate the number of stable phenotypes a cell can adopt and affect cell fate decisions.

Contribution

It demonstrates that energy availability critically modulates decision-making in a general regulatory network, highlighting the importance of considering energy levels in biological processes.

Findings

Higher energy increases stable phenotypes

Energy below threshold limits cell fate options

Energy variability explains decision-making variability

Abstract

Cells are able to generate phenotypic diversity both during development and in response to stressful and changing environments, aiding survival. The biologically and medically vital process of a cell assuming a functionally important fate from a range of phenotypic possibilities can be thought of as a cell decision. To make these decisions, a cell relies on energy dependent pathways of signalling and expression. However, energy availability is often overlooked as a modulator of cellular decision-making. As cells can vary dramatically in energy availability, this limits our knowledge of how this key biological axis affects cell behaviour. Here, we consider the energy dependence of a highly generalisable decision-making regulatory network, and show that energy variability changes the sets of decisions a cell can make and the ease with which they can be made. Increasing intracellular energy levels can increase the number of stable phenotypes it can generate, corresponding to increased decision-making capacity. For this decision-making architecture, a cell with intracellular energy below a threshold is limited to a singular phenotype, potentially forcing the adoption of a specific cell fate. We suggest that common energetic differences between cells may explain some of the observed variability in cellular decision-making, and demonstrate the importance of considering energy levels in several diverse biological decision-making phenomena.