Biomolecular condensates form spatially inhomogeneous network fluids

Furqan Dar, Samuel R. Cohen, Diana M. Mitrea, Aaron H. Phillips, Gergely Nagy, Wellington C. Leite, Christopher B. Stanley, Jeong-Mo Choi (), Richard W. Kriwacki () and Rohit V. Pappu ()
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Furqan Dar: Washington University in St. Louis
Samuel R. Cohen: Washington University in St. Louis
Diana M. Mitrea: Dewpoint Therapeutics Inc.
Aaron H. Phillips: St. Jude Children’s Research Hospital
Gergely Nagy: Oak Ridge National Laboratory
Wellington C. Leite: Oak Ridge National Laboratory
Christopher B. Stanley: Oak Ridge National Laboratory
Jeong-Mo Choi: Pusan National University
Richard W. Kriwacki: St. Jude Children’s Research Hospital
Rohit V. Pappu: Washington University in St. Louis

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights suggest that condensates formed by multivalent proteins share features with network fluids formed by systems such as patchy or hairy colloids.

Date: 2024
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DOI: 10.1038/s41467-024-47602-z

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