Limiting Energy Dissipation Induces Glassy Kinetics in Single-Cell High-Precision Responses

Area of Science:

• Cellular signaling dynamics
• Non-equilibrium thermodynamics in biology
• Immunology and T cell activation

Background:

• Single cells utilize dissipative, out-of-thermodynamic-equilibrium processes for precise signaling.
• Metabolic state can limit the free energy available for these essential cellular processes.

Purpose of the Study:

• To investigate how limited energy dissipation affects the kinetics of high-precision cellular responses.
• To analyze the impact on early-time T cell signaling using a kinetic proofreading model.

Main Methods:

• Employed exact analytical calculations.
• Utilized numerical simulations of a kinetic proofreading scheme in a T cell signaling model.

Main Results:

• Limited dissipation qualitatively alters single-cell kinetics, leading to slower response times.
• Observed emergence of significant cell-to-cell variations in molecular copy numbers.
• Identified temporally correlated stochastic events (dynamic facilitation) and ergodicity breaking.

Conclusions:

• Energy dissipation constraints fundamentally alter single-cell signaling kinetics and introduce variability.
• These constraints pose challenges in extrapolating single-cell behavior from population-level measurements.
• Findings extend beyond T cell discrimination to fundamental principles of cellular information processing.