Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles

Ming Tzo Wei, Shana Elbaum-Garfinkle, Alex S. Holehouse, Carlos Chih Hsiung Chen, Marina Feric, Craig B. Arnold, Rodney D. Priestley, Rohit V. Pappu, Clifford Paul Brangwynne

Research output: Contribution to journalArticlepeer-review

369 Scopus citations


Many intracellular membraneless organelles form via phase separation of intrinsically disordered proteins (IDPs) or regions (IDRs). These include the Caenorhabditis elegans protein LAF-1, which forms P granule-like droplets in vitro. However, the role of protein disorder in phase separation and the macromolecular organization within droplets remain elusive. Here, we utilize a novel technique, ultrafast-scanning fluorescence correlation spectroscopy, to measure the molecular interactions and full coexistence curves (binodals), which quantify the protein concentration within LAF-1 droplets. The binodals of LAF-1 and its IDR display a number of unusual features, including 'high concentration' binodal arms that correspond to remarkably dilute droplets. We find that LAF-1 and other in vitro and intracellular droplets are characterized by an effective mesh size of ∼3-8 nm, which determines the size scale at which droplet properties impact molecular diffusion and permeability. These findings reveal how specific IDPs can phase separate to form permeable, lowdensity (semi-dilute) liquids, whose structural features are likely to strongly impact biological function.

Original languageEnglish (US)
Article number2803
JournalNature chemistry
Issue number11
StatePublished - 2017

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Chemical Engineering


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