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Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates

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Alberti, Simon, Gladfelter, Amy, Mittag, Tanja·2019·Cell
DOI 10.1016/j.cell.2018.12.035PMC PMC6445271
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Abstract

Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells. This realization has motivated major efforts to delineate the function of such biomolecular condensates in normal cells and their roles in contexts ranging from development to age-related disease. There is great interest in understanding the underlying biophysical principles and the specific properties of biological condensates with the goal of bringing insights into a wide range of biological processes and systems. The explosion of physiological and pathological contexts involving LLPS requires clear standards for their study. Here, we propose guidelines for rigorous experimental characterization of LLPS processes in vitro and in cells, discuss the caveats of common experimental approaches, and point out experimental and theoretical gaps in the field.

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  • Commonly used in vivo approaches such as FRAP and sensitivity to 1,6-hexanediol are not always indicative of LLPS.

    “commonly used in vivo approaches like fast fluorescence recovery after photobleaching (FRAP) and sensitivity to treatment with 1,6-hexanediol are not always indicative of LLPS [423].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [423]

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Authors
Alberti, S., Gladfelter, A., & Mittag, T.
Affiliations
  • Max Planck Institute of Molecular Cell Biology and Genetics (DE)
  • University of North Carolina at Chapel Hill (US)
  • St. Jude Children's Research Hospital (US)
Corresponding author
  • Alberti, Simon
  • Gladfelter, Amy
  • Mittag, Tanja
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2019-01
Volume
176
Issue
3
Pages
419-434
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2018.12.035
PMC
PMC6445271
OpenAlex
W2914907359
Cited by
2,856
References
4
Citations by year
2026: 381 · 2025: 498 · 2024: 441 · 2023: 418 · 2022: 392 · 2021: 382 · 2020: 248 · 2019: 94 · 2018: 1
FWCI
24.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • European Research Council (725836)
  • National Institutes of Health (R01GM112846)
  • Human Frontier Science Program (RGP0034/2017)
  • Howard Hughes Medical Institute
  • Volkswagen Foundation
  • St. Jude Children's Research Hospital
  • Bundesministerium für Bildung und Forschung (01ED1601A, 01EK1606C)
  • Max-Planck-Gesellschaft
  • EU Joint Programme – Neurodegenerative Disease Research
  • American Lebanese Syrian Associated Charities (GM R01-GM081506)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
liquid-liquid phase separation, biomolecular condensates, biophysical principles, age-related diseases, developmental biology
MeSH terms
Cell Physiological Phenomena, Liquid-Liquid Extraction, Liquid Phase Microextraction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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