Reversible Kinetic Trapping of FUS Biomolecular Condensates

  • Sayantan Chatterjee
    Department of Biomedical Engineering University of Texas at Austin 107 W. Dean Keeton Rd. Austin TX 78712 USA
  • Yelena Kan
    Department of Biomedical Engineering University of Texas at Austin 107 W. Dean Keeton Rd. Austin TX 78712 USA
  • Mateusz Brzezinski
    Department of Biomedical Engineering University of Texas at Austin 107 W. Dean Keeton Rd. Austin TX 78712 USA
  • Kaloian Koynov
    Max Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 Germany
  • Roshan Mammen Regy
    Artie McFerrin Department of Chemical Engineering Texas A&M University 200 Jack E. Brown Engineering Building College Station TX 77843 USA
  • Anastasia C. Murthy
    Department of Molecular Biology, Cell Biology, and Biochemistry Brown University 70 Ship Street Providence RI 02912 USA
  • Kathleen A. Burke
    Department of Molecular Biology, Cell Biology, and Biochemistry Brown University 70 Ship Street Providence RI 02912 USA
  • Jasper J. Michels
    Max Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 Germany
  • Jeetain Mittal
    Artie McFerrin Department of Chemical Engineering Texas A&M University 200 Jack E. Brown Engineering Building College Station TX 77843 USA
  • Nicolas L. Fawzi
    Department of Molecular Biology, Cell Biology, and Biochemistry Brown University 70 Ship Street Providence RI 02912 USA
  • Sapun H. Parekh
    Department of Biomedical Engineering University of Texas at Austin 107 W. Dean Keeton Rd. Austin TX 78712 USA

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<jats:title>Abstract</jats:title><jats:p>Formation of membrane‐less organelles by self‐assembly of disordered proteins can be triggered by external stimuli such as pH, salt, or temperature. These organelles, called biomolecular condensates, have traditionally been classified as liquids, gels, or solids with limited subclasses. Here, the authors show that a thermal trigger can lead to formation of at least two distinct liquid condensed phases of the fused in sarcoma low complexity (FUS LC) domain. Forming FUS LC condensates directly at low temperature leads to formation of metastable, kinetically trapped condensates that show arrested coalescence, escape from which to untrapped condensates can be achieved via thermal annealing. Using experimental and computational approaches, the authors find that molecular structure of interfacial FUS LC in kinetically trapped condensates is distinct (more <jats:italic>β</jats:italic>‐sheet like) compared to untrapped FUS LC condensates. Moreover, molecular motion within kinetically trapped condensates is substantially slower compared to that in untrapped condensates thereby demonstrating two unique liquid FUS condensates. Controlling condensate thermodynamic state, stability, and structure with a simple thermal switch may contribute to pathological protein aggregate stability and provides a facile method to trigger condensate mixing for biotechnology applications.</jats:p>

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