Enzyme-driven phase separation

Abstract

The formation of polarized signaling domains on cell membranes is a fundamental example of biological pattern formation. While such patterns resemble structures from equilibrium phase separation, they are intrinsically non-equilibrium, driven by energy-consuming enzymatic cycles that switch molecules like phosphoinositides or small GTPases between distinct states. Here, we develop a minimal model of this enzyme-driven phase ordering process. Starting from microscopic reaction kinetics, we derive a mesoscopic theory that belongs to the class of active Model A with a global constraint. This framework yields an explicit mean-field phase diagram and closed-form expressions for key observables, such as interfacial tension, domain fractions, and phase coexistence boundaries, in terms of kinetic rates. In this context, phase coexistence is controlled by non-equilibrium parameters like catalytic rates and enzymatic asymmetry, rather than equilibrium parameters such as saturation concentrations. The resulting phase-separated domains rapidly exchange material with their surroundings. Their maintenance requires a continuous power input determined by enzymatic kinetics. The predicted phenomenology is consistent with experimental observations on reconstituted systems of phosphoinositide and Rab5 membrane patterning. We further study how metastable uniform states decay via nucleation of minority-phase domains and subsequent coarsening, driven by an effective interfacial tension. Using large deviation theory, we derive the critical nucleation radius under the action of the intrinsic, multiplicative chemical noise. The analytical results are quantitatively confirmed by stochastic simulations of the process. Our work provides a theoretical framework identifying key biochemical parameters controlling active phase separation on membrane scaffolds, offering testable predictions for experiments.

References in corpus (27)

• The large deviation approach to statistical mechanics
• Motility-Induced Phase Separation
• Scalar ${\varphi }^4$ field theory for active-particle phase separation
• Physics of Active Emulsions
• Nonequilibrium Physics in Biology
• The non-linear q-voter model
• A mass conserved reaction-diffusion system captures properties of cell polarity
• Self-organization principles of intracellular pattern formation
• Thermodynamic pathways to genome spatial organization in the cell nucleus
• Nonlinear Voter Models: The Transition from Invasion to Coexistence
• Phase-space geometry of mass-conserving reaction-diffusion dynamics
• Min-oscillations in Escherichia coli induced by interactions of membrane-bound proteins
• Enzyme-enriched condensates show self-propulsion, positioning, and coexistence
• Wavelength selection by interrupted coarsening in reaction-diffusion systems
• Classical Nucleation Theory for Active Fluid Phase Separation
• Active phase separation: new phenomenology from non-equilibrium physics
• Coherent-state path integral versus coarse-grained effective stochastic equation of motion: From reaction diffusion to stochastic sandpiles
• Phase segregation of passive advective particles in an active medium
• Nucleation of chemically active droplets
• Active emulsions in living cell membranes driven by contractile stresses and transbilayer coupling
• Universal features of cell polarization processes
• Patch coalescence as a mechanism for eukaryotic directional sensing
• Coarsening and wavelength selection far from equilibrium: a unifying framework based on singular perturbation theory
• A symmetry breaking mechanism for epithelial cell polarization
• Optimality in self-organized molecular sorting
• Universal limiting behaviour of reaction-diffusion systems with conservation laws
• Species interconversion of deformable particles yields transient phase separation