Biomolecular condensates undergo a generic shear-mediated liquid-to-solid transition

Research output: Contribution to journalArticlepeer-review

Authors

  • Yi Shen
  • Francesco Simone Ruggeri
  • Ayaka Kamada
  • Seema Qamar
  • Aviad Levin
  • Christiane Iserman
  • Simon Alberti
  • Peter St George-Hyslop
  • Tuomas P J Knowles

Colleges, School and Institutes

External organisations

  • Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
  • University of Cambridge
  • School of Chemical Engineering
  • Max Planck Institute of Molecular Cell Biology and Genetics

Abstract

Membrane-less organelles resulting from liquid-liquid phase separation of biopolymers into intracellular condensates control essential biological functions, including messenger RNA processing, cell signalling and embryogenesis1-4. It has recently been discovered that several such protein condensates can undergo a further irreversible phase transition, forming solid nanoscale aggregates associated with neurodegenerative disease5-7. While the irreversible gelation of protein condensates is generally related to malfunction and disease, one case where the liquid-to-solid transition of protein condensates is functional, however, is that of silk spinning8,9. The formation of silk fibrils is largely driven by shear, yet it is not known what factors control the pathological gelation of functional condensates. Here we demonstrate that four proteins and one peptide system, with no function associated with fibre formation, have a strong propensity to undergo a liquid-to-solid transition when exposed to even low levels of mechanical shear once present in their liquid-liquid phase separated form. Using microfluidics to control the application of shear, we generated fibres from single-protein condensates and characterized their structural and material properties as a function of shear stress. Our results reveal generic backbone-backbone hydrogen bonding constraints as a determining factor in governing this transition. These observations suggest that shear can play an important role in the irreversible liquid-to-solid transition of protein condensates, shed light on the role of physical factors in driving this transition in protein aggregation-related diseases and open a new route towards artificial shear responsive biomaterials.

Details

Original languageEnglish
Pages (from-to)841-847
Number of pages7
JournalNature Nanotechnology
Volume15
Issue number10
Early online date13 Jul 2020
Publication statusPublished - Oct 2020