Phase separation vs aggregation behavior for model disordered proteins*

Liquid-liquid phase separation (LLPS) is widely utilized by the cell to organize and regulate various biochemical processes. In this talk, we present how sequence distribution, sticker fraction and chain length impact the formation of finite-size aggregates which can preempt macroscopic phase separation for some sequences. We demonstrate that a normalized sequence charge decoration (SCD) parameter establishes a "soft" predictive criterion for distinguishing when a model protein undergoes macroscopic phase separation vs finite aggregation. Furthermore, this order parameter was found to be strongly correlated to the critical density for phase separation, highlighting an unambiguous connection between sequence distribution and condensed phase density. Results obtained from an analysis of the order parameter reveals that at sufficiently long chain lengths, the vast majority of sequences are likely to phase separate. Our results suggest classical LLPS should be the primary phase transition for disordered proteins when short-ranged attractive interactions dominate and hints at a possible reason behind recent findings of widespread phase separation throughout living cells.