▎ 摘　　要

Protein liquid-liquid phase separation (LLPS)plays a crucialrole in mediating dynamic assembly of different membraneless organellessuch as stress granules (SGs). Dysregulation of dynamic protein LLPSleads to aberrant phase transition and amyloid aggregation which isclosely associated with neurodegenerative diseases. In this study,we found that three types of graphene quantum dots (GQDs) exhibitpotent activity in preventing SG formation and promoting SG disassembly.We next demonstrate that GQDs can directly interact with the SGs-containingprotein fused in sarcoma (FUS), inhibit and reverse FUS LLPS, andprevent its abnormal phase transition. Moreover, GQDs display superioractivity in preventing amyloid aggregation of FUS and disaggregatingpreformed FUS fibrils. Mechanistic study further demonstrates thatGQDs with different edge-site exhibit distinct binding affinity toFUS monomers and fibrils, which accounts for their distinct activitiesin modulating FUS LLPS and fibrillation. Our work reveals the potentcapability of GQDs in modulating SG assembly, protein LLPS, and fibrillationand sheds light on rational design of GQDs as effective modulatorsof protein LLPS for therapeutics application.