Evidence map›Paper›PMID 33893091›Full record

ArticleScience advances2021

Hydraulic resistance induces cell phenotypic transition in confinement.

Runchen Zhao, Siqi Cui, Zhuoxu Ge, Yuqi Zhang, Kaustav Bera, Lily Zhu, Sean X Sun, Konstantinos Konstantopoulos

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. The Rise of Mechanobiology for Advanced Cell Engineering and Manufacturing.Advanced materials (Deerfield Beach, Fla.) · 2025
    Review
  5. Article
  6. Review
  7. Confined Migration Drives Stem Cell Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  8. Review
  9. Article
  10. Physical principles and mechanisms of cell migration.npj biological physics and mechanics · 2025
    Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  16. Article
  17. Hydrostatic pressure as a driver of cell and tissue morphogenesis.Seminars in cell & developmental biology · 2022
    Review
  18. Article
  19. Article
  20. 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

8 authors.

Runchen ZhaoDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0001-8673-3990
Siqi CuiDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Zhuoxu GeJohns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Yuqi ZhangDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0001-8482-1989
Kaustav BeraDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-0962-4368
Lily ZhuDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-8804-6630
Sean X SunDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-9077-7088
Konstantinos KonstantopoulosDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA. konstant@jhu.edu.

Funding

The Role of Physical Cues in Collective Cell InvasionU54CA210173 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2016 to 2020
$9.9M
Development of high throughput screening technologies in breast cancerR01CA183804 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS, KONTROGIANNI-KONSTANTOPOULOS, AIKATERINI · 2015 to 2019
$3.5M
The Role of Hydraulic Pressure in the Osmotic Engine Model of Cell MigrationR01GM134542 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI SEAN X SUN · 2019 to 2026
$2.1M
NCI NIH HHS R01 CA183804NCI NIH HHS U54 CA210173NIGMS NIH HHS R01 GM134542
6 · The paper itself

Abstract

Cells penetrating into confinement undergo mesenchymal-to-amoeboid transition. The topographical features of the microenvironment expose cells to different hydraulic resistance levels. How cells respond to hydraulic resistance is unknown. We show that the cell phenotype shifts from amoeboid to mesenchymal upon increasing resistance. By combining automated morphological tracking and wavelet analysis along with fluorescence recovery after photobleaching (FRAP), we found an oscillatory phenotypic transition that cycles from blebbing to short, medium, and long actin network formation, and back to blebbing. Elevated hydraulic resistance promotes focal adhesion maturation and long actin filaments, thereby reducing the period required for amoeboid-to-mesenchymal transition. The period becomes independent of resistance upon blocking the mechanosensor TRPM7. Mathematical modeling links intracellular calcium oscillations with actomyosin turnover and force generation and recapitulates experimental data. We identify hydraulic resistance as a critical physical cue controlling cell phenotype and present an approach for connecting fluorescent signal fluctuations to morphological oscillations.

Identifiers

PMID33893091
PMCPMC8064631

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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.