Chemically Fueled, Active Droplets Prevent the Aging of Peptides into Amyloid-Like Fibers.

ABSTRACT: Protein aggregation is a hallmark of molecular aging and is implicated in various neurodegenerative diseases. Aggregation proceeds via autocatalytic, thermodynamically favored pathways. Yet in living systems, dynamic, active regulation and compartmentalization─such as in biomolecular condensates─can suppress or delay such irreversible assembly. Here, we describe a peptide that exhibits pathway-dependent self-assembly into either amyloid-like fibers or fuel-driven droplets. The peptide was designed to undergo chemical activation via a carbodiimide-driven reaction cycle, which transiently neutralizes its overall charge and promotes droplet formation. In the absence of fuel, the peptide slowly self-assembles into stable fibers through an autocatalytic process resembling amyloid aging. However

SUBMITTER: Wenisch M 

PROVIDER: S-EPMC12636012 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature