Condensate rheology affects the irreversible formation of fibrils

Membrane-less compartments regulate biochemical processes in living cells. These condensates exhibit a complex rheology including viscoelastic, glassy and gel-like behaviour. It has been suggested that condensate rheology plays an important role in regulating physiological but also aberrant processes such as the irreversible aggregation into fibrils. Here, we investigate how rheological properties of liquid condensates can control fibril aggregation. To address this question, we present a kinetic theory of fibril aggregation in the presence of phase-separated condensates and account for condensate rheology by a mobility that depends on the aggregate size. Our theory reveals that aggregation is strongly affected by condensate rheology. For example, for gel-like condensates giving rise to a reptation-like kinetics of fibrils, we show that aggregates are strongly enriched inside condensates and the average number of aggregates can be reduced. Our results suggest a possible physical mechanism for how living cells may control fibril aggregation by exploiting phase separation and altering the rheological properties of the liquid condensates.

WP thanks the Herchel Smith Fund.