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Nat Chem. 2017 Nov;9(11):1118-1125. doi: 10.1038/nchem.2803. Epub 2017 Jun 26.

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

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Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, USA.
Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in Saint Louis, Saint Louis, Missouri 63130, USA.
Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544, USA.


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, low-density (semi-dilute) liquids, whose structural features are likely to strongly impact biological function.

[Indexed for MEDLINE]

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