Spatial control of irreversible protein aggregation

Liquid cellular compartments form in the cytoplasm and can regulate aberrant protein aggregation. Yet the mechanisms by which these compartments affect protein aggregation remain unknown. Here, we combine kinetic theory of protein aggregation and liquid-liquid phase separation to study the spatial control of irreversible protein aggregation in the presence of liquid compartments. We find that even for weak interactions aggregates strongly enrich inside the liquid compartment relative to the surrounding cytoplasm. This enrichment is caused by a positive feedback mechanism of aggregate nucleation and growth driven by a flux maintaining the phase equilibrium between the compartment and the cytoplasm. Our model establishes a link between specific aggregating systems and the physical conditions maximizing aggregate enrichment in the compartment. The underlying mechanism of aggregate enrichment could be used to confine cytotoxic protein aggregates inside droplet-like compartments but may also represent a common mechanism to spatially control irreversible chemical reactions in general.