Fibres and glasses are competing material states in protein condensation

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Liru Feng - , Leiden University (Author)
  • Ryota Takaki - , Max-Planck-Institute for the Physics of Complex Systems (Author)
  • Iain Muntz - , Leiden University (Author)
  • Lionel Ndamba - , Leiden University (Author)
  • Martine Ruer-Gruß - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Frank Jülicher - , Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), TUD Dresden University of Technology (Author)
  • Louise Jawerth - , Leiden University (Author)

Abstract

Dense, well-ordered material states of proteins form the amyloid fibres that are indicative of neurodegenerative disease in the brain. In addition to forming amyloid fibres, some of these proteins comprise condensates that are initially liquid-like but evolve to a glassy, solid-like phase. Fibre growth requires a large supply of monomers, and so it is often speculated that fibres emerge from within a dense condensate as it ages and its microscopic dynamics slow into a glassy state. Here we show that, in the model system Fused in Sarcoma (FUS), fibres grow overwhelmingly in the dilute phase surrounding the condensates; concurrently, the condensates evolve to a glassy arrested solid. The resulting protein fibres and glassy condensates are both distinct solid-like phases that coexist but do not directly interconvert. These findings suggest that there may be two competitive ageing pathways in FUS condensation that are linked through phase separation kinetics.

Details

Original languageEnglish
JournalNature physics
Publication statusE-pub ahead of print - Oct 2026
Peer-reviewedYes

Keywords

ASJC Scopus subject areas