Sequence-encoded patterning of stickers modulates biomolecular condensate reconfiguration in IDP systems

Abstract

Intrinsically disordered proteins (IDPs) exert pivotal roles in Phase Separation Coupled to Percolation (PSCP), a process that drives the formation of functional biomolecular condensates linked to diverse cellular physiological activities. In this study, we investigate how sequence-encoded mesoscopic patterning modulates PSCP in IDP systems by leveraging the classic stickers-and-spacers framework, combined with coarse-grained molecular dynamics simulations. Intriguingly, our analysis demonstrates that the distribution of stickers plays important roles: compactness of sticker arrangement on IDPs exerts a substantial influence on IDP clustering process, while the patterning heterogeneity of the arrangement additionally impacts the morphology of the resulting aggregations. Subsequent findings elucidate that sparse and homogeneous stickers facilitate the emergence of robust aggregation, whereas proximal sequential organization directly induces dispersed and small clusters. These discoveries are validated through the statistical quantification of void volume fraction ϕvoid (serving as a referential measure for condensate maturation) in conjunction with the quantification of the total stickers present on the cluster surfaces. Collectively, this work may shed new lights on the underlying mechanism for regulating IDP-mediated phase separation.