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

Abstract

AO_SCPLOWBSTRACTC_SCPLOWMany 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.