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  Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation

Lan, C., Kim, J., Ulferts, S., Aprile-Garcia, F., Weyrauch, S., Anandamurugan, A., et al. (2023). Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation. Nature Communications, 14: 4831. doi:10.1038/s41467-023-40540-2.

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10.1038_s41467-023-40540-2.pdf (Publisher version), 3MB
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 Creators:
Lan, Chenyang1, Author
Kim, Juhyeong1, Author
Ulferts, Svenja1, Author
Aprile-Garcia, Fernando2, Author
Weyrauch, Sophie1, Author
Anandamurugan, Abhinaya1, Author
Grosse, Robert1, Author
Sawarkar, Ritwick1, Author
Reinhardt, Aleks1, Author
Hugel, Thorsten1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              

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Free keywords: Biological fluorescence, Biophysical chemistry, Mechanism of action
 Abstract: Our current understanding of biomolecular condensate formation is largely based on observing the final near-equilibrium condensate state. Despite expectations from classical nucleation theory, pre-critical protein clusters were recently shown to form under subsaturation conditions in vitro; if similar long-lived clusters comprising more than a few molecules are also present in cells, our understanding of the physical basis of biological phase separation may fundamentally change. Here, we combine fluorescence microscopy with photobleaching analysis to quantify the formation of clusters of NELF proteins in living, stressed cells. We categorise small and large clusters based on their dynamics and their response to p38 kinase inhibition. We find a broad distribution of pre-condensate cluster sizes and show that NELF protein cluster formation can be explained as non-classical nucleation with a surprisingly flat free-energy landscape for a wide range of sizes and an inhibition of condensation in unstressed cells.

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Language(s): eng - English
 Dates: 2023-08-15
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-023-40540-2
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 14 Sequence Number: 4831 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723