First passage and cooperativity of queuing kinetics

Area of Science:

• Biophysics
• Chemical Kinetics
• Systems Biology

Background:

• Ligand-receptor interactions are fundamental in biological and chemical systems.
• Understanding the kinetics of binding and unbinding is crucial for predicting system behavior.
• Multiple ligands can interact with receptors in various orders, influencing overall dynamics.

Purpose of the Study:

• To model and compare the kinetics of ligand-receptor systems with random versus sequential binding.
• To determine equilibrium receptor occupation and the time to first complete receptor filling.
• To investigate the influence of cooperativity and binding energy on these kinetic processes.

Main Methods:

• Development of kinetic models for ligand-receptor interactions.
• Simulation and analysis of receptor occupancy over time.
• Comparison of outcomes for random and sequential binding pathways.

Main Results:

• Sequential binding results in higher equilibrium receptor saturation compared to random binding.
• For low cooperativity, random binding can achieve full receptor occupancy faster than sequential binding.
• A 'kinetic trap' phenomenon emerges near critical binding energies for N >= 8, significantly slowing random processes.

Conclusions:

• Cooperativity and binding order have a complex interplay affecting ligand-receptor kinetics.
• These findings have implications for understanding chemical binding, molecular nucleation, and assembly processes.
• The study highlights how subtle kinetic differences can lead to distinct system behaviors.