Evidence map›Paper›PMID 30716021›Full record

ArticleeLife2019

A first order phase transition mechanism underlies protein aggregation in mammalian cells.

Arjun Narayanan, Anatoli Meriin, J Owen Andrews, Jan-Hendrik Spille, Michael Y Sherman, Ibrahim I Cisse

Abstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing 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

59 citing papers in PubMed.

  1. Distinguishing near- versus off-critical phase behaviors of intrinsically disordered proteins.Reports on progress in physics. Physical Society (Great Britain) · 2026
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  4. Review
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  7. Oxidative environments promote the formation of detergent-resistant IgG aggregates mediated by Cu(II) assessed by optical density: implications in vivo.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2025
    Article
  8. Article
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  11. Physics of Protein Aggregation in Normal and Accelerated Brain Aging.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
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  13. Article
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  15. Article
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  19. Review
  20. Differential roles of putative arginine fingers of AAAbioRxiv : the preprint server for biology · 2024
    Article
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

6 authors.

Arjun NarayananDepartment of Physics, Massachusetts Institute of Technology, Cambridge, United States.ORCID 0000-0002-2269-3253
Anatoli MeriinDepartment of Biochemistry, Boston University School of Medicine, Boston, United States.ORCID 0000-0003-0087-814X
J Owen AndrewsDepartment of Physics, Massachusetts Institute of Technology, Cambridge, United States.
Jan-Hendrik SpilleDepartment of Physics, Massachusetts Institute of Technology, Cambridge, United States.
Michael Y ShermanDepartment of Molecular Biology, Ariel University, Ariel, Israel.
Ibrahim I CisseDepartment of Physics, Massachusetts Institute of Technology, Cambridge, United States.ORCID 0000-0002-8764-1809

Funding

IMAGING TRANSCRIPTION WITH SINGLE MOLECULE RESOLUTION IN LIVE MAMMALIAN CELLSDP2CA195769 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CISSE, IBRAHIM · 2014 to 2014
$2.3M
NCI NIH HHS DP2 CA195769NIH HHS DP2CA195769
6 · The paper itself

Abstract

The formation of misfolded protein aggregates is a hallmark of neurodegenerative diseases. The aggregate formation process exhibits an initial lag phase when precursor clusters spontaneously assemble. However, most experimental assays are blind to this lag phase. We develop a quantitative assay based on super-resolution imaging in fixed cells and light sheet imaging of living cells to study the early steps of aggregation in mammalian cells. We find that even under normal growth conditions mammalian cells have precursor clusters. The cluster size distribution is precisely that expected for a so-called super-saturated system in first order phase transition. This means there exists a nucleation barrier, and a critical size above which clusters grow and mature. Homeostasis is maintained through a Szilard model entailing the preferential clearance of super-critical clusters. We uncover a role for a putative chaperone (RuvBL) in this disassembly of large clusters. The results indicate early aggregates behave like condensates. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Indexed as

Protein FoldingCell Line, TumorHumansKineticsNeurodegenerative DiseasesPhase TransitionProtein AggregatesProtein Aggregation, PathologicalProtein Aggregatesaggregationhumanlive cell imagingneurodegenerationphase separationphysics of living systemssingle moleculesuper-resolution

Identifiers

PMID30716021
PMCPMC6361590

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.