Confinement and diffusion modulate bistability and stochastic switching in a reaction network with positive feedback

Area of Science:

• Systems biology
• Cellular signaling
• Computational biophysics

Background:

• Positive feedback loops are crucial in signal transduction, enabling bistability and signal propagation.
• The influence of physical cellular constraints (e.g., confinement, molecular mobility) on these networks is not fully understood.

Purpose of the Study:

• To investigate how physical properties of the cellular environment affect positive feedback signaling networks.
• To explore the roles of system size, shape, and molecular mobility in network dynamics.

Main Methods:

• Employed stochastic, spatially resolved kinetic Monte Carlo simulations.
• Varied system size, shape, and molecular diffusion coefficients.

Main Results:

• Physical properties significantly alter bistability and stochastic switching compared to well-mixed models.
• Systems with identical volumes but different shapes exhibit distinct behaviors.
• Switching occurs via molecular cluster formation and growth, with frequency dependent on diffusion.

Conclusions:

• Cellular confinement and protein mobility critically influence emergent properties of positive feedback networks.
• These factors modulate molecular concentrations, diffusion-influenced rates, and spatiotemporal correlations.
• Provides a framework for understanding physical constraints on signaling network dynamics.