Stochastic transitions in a bistable reaction system on the membrane

Area of Science:

• Biophysics
• Chemical Kinetics
• Cellular Signaling

Background:

• Transitions between steady states in multi-stable systems are typically driven by stochastic switching in well-mixed conditions.
• In cellular environments with limited diffusion, traveling waves can also mediate transitions between steady states.
• Understanding the interplay of these transition modes is crucial for comprehending cellular dynamics.

Purpose of the Study:

• To investigate the interplay between stochastic switching and traveling wave propagation in a bistable kinase-phosphatase system on the plasma membrane.
• To explore how finite diffusion affects system behavior compared to the well-mixed regime.
• To elucidate the mechanism by which local substrate immobilization can lead to global activation.

Main Methods:

• Microscopic kinetic Monte Carlo simulations on a hexagonal lattice.
• Modeling a prototype bistable system of kinase-phosphatase interactions.
• Analysis of spatially extended systems with finite diffusion.

Main Results:

• Spatially extended systems with finite diffusion exhibit qualitatively different behavior than well-mixed systems.
• Chemical traveling waves can propagate and activate larger compartments even if small subcompartments remain inactive.
• Spontaneous activation onset is more probable in subdomains with slower diffusion, initiating activating waves.

Conclusions:

• Local substrate immobilization can induce global activation of membrane proteins via stochastic fluctuations followed by traveling wave propagation.
• This mechanism highlights a novel pathway for signal propagation in spatially constrained cellular environments.
• Finite diffusion plays a critical role in enabling traveling wave-mediated transitions between steady states.