PROTEIN-PROTEIN INTERACTION NETWORKS CAN BE HIGHLY SENSITIVE TO THE MEMBRANE PHASE TRANSITION

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Protein-protein interactions (PPIs) are crucial for cellular signaling, often occurring within the plasma membrane.
• Lipid domains (rafts) within the membrane are known to influence membrane-bound signaling processes.
• Understanding how membrane properties affect PPI dynamics is essential for deciphering cellular functions.

Purpose of the Study:

• To investigate the impact of lipid domain size changes on PPI network rates and outcomes.
• To model how perturbations to membrane criticality affect protein interactions.
• To explore the formation of non-equilibrium domains ('pockets') driven by thermodynamic and kinetic factors.

Main Methods:

• Development of a computational model.
• Utilizing Monte Carlo simulations to study membrane criticality and domain formation.
• Analyzing the sensitivity of PPI networks to thermodynamic parameters near the critical point.

Main Results:

• PPI network activity is highly sensitive to thermodynamic parameters near the membrane's critical point.
• Protein-protein interactions can alter component partitioning, leading to the formation of out-of-equilibrium domains ('pockets').
• These 'pockets' form due to a combination of thermodynamic interactions and kinetic sorting.

Conclusions:

• Membrane criticality significantly influences the behavior and outcomes of protein-protein interaction networks.
• Perturbations affecting critical behavior can lead to sensitive and altered PPI network dynamics.
• The formation of 'pockets' highlights complex interplay between thermodynamics and kinetics in membrane organization.