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; Rohit V. Pappu

doi:10.1038/s41467-024-47602-z

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
, Rohit V. Pappu

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English
Article number	3413
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-47602-z
State	Published - Dec 2024

Funding

This work was supported by the St. Jude Children’s Research Hospital Research Collaborative on the Biology and Biophysics of RNP granules (to R.V.P. and R.W.K.), the US National Science Foundation (MCB-2227268 to R.V.P.), the US National Institutes of Health (NIGMS R01 GM115634 and R35 GM131891 to R.W.K., and NCI P30 CA021765 to St. Jude Children’s Research Hospital), ALSAC (supporting studies at St. Jude Children’s Research Hospital), and National Research Foundation (NRF) grants of Korea (2021R1C1C1010943 and 2022R1A4A1033471 to J.-M.C.). A portion of this research, conducted at the Oak Ridge National Laboratory (ORNL) Spallation Neutron Source, was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. S.R. Cohen acknowledges financial support via T32 EB028092 from the US National Institutes of Health. We thank Jared M. Lalmansingh for technical assistance with CAMPARI. Fluorescence microscopy images were acquired at the St. Jude Cell & Tissue Imaging Center at St. Jude Children’s Research Hospital (supported by P30 CA021765); we thank V. Frohlich, J. Peters, A. Taylor, A. Pitre, and G. Campbell for technical assistance.

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title = "Biomolecular condensates form spatially inhomogeneous network fluids",

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.",

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AU - Cohen, Samuel R.

AU - Mitrea, Diana M.

AU - Phillips, Aaron H.

AU - Nagy, Gergely

AU - Leite, Wellington C.

AU - Stanley, Christopher B.

AU - Choi, Jeong Mo

AU - Kriwacki, Richard W.

AU - Pappu, Rohit V.

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Y1 - 2024/12

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AB - 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.

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Biomolecular condensates form spatially inhomogeneous network fluids

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