Limiting energy dissipation induces glassy kinetics in single cell high precision responses

TL;DR

This paper demonstrates that limiting energy dissipation in single-cell signaling processes induces slow, variable, and correlated response kinetics, revealing fundamental challenges in interpreting single-cell data and affecting immune cell function.

Contribution

It provides an analytical and numerical study showing how energy dissipation constraints qualitatively alter single-cell response kinetics in signaling networks.

Findings

Emergence of slow response kinetics under limited dissipation

Large cell-to-cell variability in signaling responses

Temporal correlations and ergodicity breaking in cell responses

Abstract

Single cells often generate precise responses by involving dissipative out-of-thermodynamic equilibrium processes in signaling networks. The available free energy to fuel these processes could become limited depending on the metabolic state of an individual cell. How does limiting dissipation affect the kinetics of high precision responses in single cells? I address this question in the context of a kinetic proofreading scheme used in a simple model of early time T cell signaling. I show using exact analytical calculations and numerical simulations that limiting dissipation qualitatively changes the kinetics in single cells marked by emergence of slow kinetics, large cell-to-cell variations of copy numbers, temporally correlated stochastic events (dynamic facilitation), and, ergodicity breaking. Thus, constraints in energy dissipation, in addition to negatively affecting ligand discrimination in T cells, can create a fundamental difficulty in interpreting single cell kinetics from cell population level results.