Evidence map›Paper›PMID 37549257›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

The liquid-to-solid transition of FUS is promoted by the condensate surface.

Yi Shen, Anqi Chen, Wenyun Wang, Yinan Shen, Francesco Simone Ruggeri, Stefano Aime, Zizhao Wang, Seema Qamar, Jorge R Espinosa, Adiran Garaizar and 5 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

99 citing papers in PubMed.

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  16. Plant NLRs are getting into higher-order architectures.The Plant journal : for cell and molecular biology · 2026
    Review
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39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Yi ShenYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom.ORCID 0000-0002-0456-3850
Anqi ChenJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Wenyun WangJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Yinan ShenDepartment of Physics, Harvard University, Cambridge, MA 02138.
Francesco Simone RuggeriYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom.ORCID 0000-0002-1232-1907
Stefano AimeMolecular, Macromolecular Chemistry, and Materials, École Supérieure de Physique et de Chimie Industrielles Paris, CNRS, Paris Sciences & Lettres University, Paris 75005, France.ORCID 0000-0002-0357-6983
Zizhao WangJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Seema QamarCambridge Institute for Medical Research, Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
Jorge R EspinosaCavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom.ORCID 0000-0001-9530-2658
Adiran GaraizarCavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom.ORCID 0000-0002-9320-2984
Peter St George-HyslopCambridge Institute for Medical Research, Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0XY, United Kingdom.ORCID 0000-0003-0796-7209
Rosana Collepardo-GuevaraYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom.ORCID 0000-0003-1781-7351
David A WeitzJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Daniele VigoloThe University of Sydney Nano Institute, The University of Sydney, Sydney, NSW 2006, Australia.ORCID 0000-0002-8265-9882
Tuomas P J KnowlesYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom.

Funding

Genomic Characterization of Alzheimer Disease Risk in Admixed Populations with Native American and Southern European Genetic AncestryR01AG070864 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Margaret A. Pericak-Vance, FARID RAJABLI · 2021 to 2026
$12.1M
Alzheimer variants: Propagation of shared functional changes across cellular networksU01AG072572 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DE JAGER, PHILIP L, ST GEORGE-HYSLOP, PETER HENRY · 2021 to 2025
$8.5M
NIA NIH HHS R01 AG070864NIA NIH HHS U01 AG072572Wellcome Trust 203249/Z/16/Z
6 · The paper itself

Abstract

A wide range of macromolecules can undergo phase separation, forming biomolecular condensates in living cells. These membraneless organelles are typically highly dynamic, formed reversibly, and carry out essential functions in biological systems. Crucially, however, a further liquid-to-solid transition of the condensates can lead to irreversible pathological aggregation and cellular dysfunction associated with the onset and development of neurodegenerative diseases. Despite the importance of this liquid-to-solid transition of proteins, the mechanism by which it is initiated in normally functional condensates is unknown. Here we show, by measuring the changes in structure, dynamics, and mechanics in time and space, that single-component FUS condensates do not uniformly convert to a solid gel, but rather that liquid and gel phases coexist simultaneously within the same condensate, resulting in highly inhomogeneous structures. Furthermore, our results show that this transition originates at the interface between the condensate and the dilute continuous phase, and once initiated, the gelation process propagates toward the center of the condensate. To probe such spatially inhomogeneous rheology during condensate aging, we use a combination of established micropipette aspiration experiments together with two optical techniques, spatial dynamic mapping and reflective confocal dynamic speckle microscopy. These results reveal the importance of the spatiotemporal dimension of the liquid-to-solid transition and highlight the interface of biomolecular condensates as a critical element in driving pathological protein aggregation.

Indexed as

Biomolecular CondensatesProtein Aggregation, PathologicalHumansMicroscopy, ConfocalRheologyRNA-Binding Protein FUSFUS protein, humanRNA-Binding Protein FUSbiomolecular condensatesopticsprotein

Identifiers

PMID37549257
PMCPMC10438845

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.