Protein-protein interaction networks can be highly sensitive to the membrane phase transition

TL;DR

This study models how membrane phase transitions influence protein-protein interactions, revealing high sensitivity near critical points and the formation of out-of-equilibrium domains, impacting cellular signaling processes.

Contribution

The paper introduces a Monte Carlo simulation framework to analyze how membrane criticality affects PPI network activity and domain formation, highlighting sensitivity to thermodynamic parameters.

Findings

PPI activity is highly sensitive near membrane critical points.

Perturbations can lead to out-of-equilibrium domain formation.

Many PPI networks' outcomes depend on membrane critical behavior.

Abstract

Many protein-protein interaction (PPI) networks take place in the fluid yet structured plasma membrane. Lipid domains, sometimes termed rafts, have been implicated in the functioning of various membrane-bound signaling processes. Here, we present a model and a Monte Carlo simulation framework to investigate how changes in the domain size that arise from perturbations to membrane criticality can lead to changes in the rate of interactions among components, leading to altered outcomes. For simple PPI networks, we show that the activity can be highly sensitive to thermodynamic parameters near the critical point of the membrane phase transition. When protein-protein interactions change the partitioning of some components, our system sometimes forms out of equilibrium domains we term pockets, driven by a mixture of thermodynamic interactions and kinetic sorting. More generally, we predict that near the critical point many different PPI networks will have their outcomes depend sensitively on perturbations that influence critical behavior.