Evidence map›Paper›PMID 36475639›Full record

ArticleACS nano2023

A Photopolymerized Hydrogel System with Dual Stiffness Gradients Reveals Distinct Actomyosin-Based Mechano-Responses in Fibroblast Durotaxis.

Reem M Hakeem, Bhagawat C Subramanian, Max A Hockenberry, Zayna T King, Mitchell T Butler, Wesley R Legant, James E Bear

Abstract read
In one paragraph

Article in ACS nano, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Microengineered Gradient Hydrogels for Mechanobiology.Advanced healthcare materials · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
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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

7 authors.

Reem M HakeemDepartment of Biochemistry and Biophysics, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.
Bhagawat C SubramanianUNC Lineberger Comprehensive Cancer Center, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0002-6976-7512
Max A HockenberryDepartment of Cell Biology and Physiology, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.
Zayna T KingDepartment of Cell Biology and Physiology, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.
Mitchell T ButlerDepartment of Cell Biology and Physiology, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.
Wesley R LegantDepartment of Pharmacology, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.
James E BearDepartment of Cell Biology and Physiology, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0002-8489-996X

Funding

Systematic Analysis of the Actin Cytoskeleton and Directed Cell MigrationR35GM130312 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JAMES E BEAR · 2019 to 2026
$4.8M
NIGMS NIH HHS R35 GM130312
6 · The paper itself

Abstract

Durotaxis, migration of cells directed by a stiffness gradient, is critical in development and disease. To distinguish durotaxis-specific migration mechanisms from those on uniform substrate stiffnesses, we engineered an all-in-one photopolymerized hydrogel system containing areas of stiffness gradients with dual slopes (steep and shallow), adjacent to uniform stiffness (soft and stiff) regions. While fibroblasts rely on nonmuscle myosin II (NMII) activity and the LIM-domain protein Zyxin, ROCK and the Arp2/3 complex are surprisingly dispensable for durotaxis on either stiffness gradient. Additionally, loss of either actin-elongator Formin-like 3 (FMNL3) or actin-bundler fascin has little impact on durotactic response on stiffness gradients. However, lack of Arp2/3 activity results in a filopodia-based durotactic migration that is equally as efficient as that of lamellipodia-based durotactic migration. Importantly, we uncover essential and specific roles for FMNL3 and fascin in the formation and asymmetric distribution of filopodia during filopodia-based durotaxis response to the stiffness gradients. Together, our tunable all-in-one hydrogel system serves to identify both conserved as well as distinct molecular mechanisms that underlie mechano-responses of cells experiencing altered slopes of stiffness gradients.

Indexed as

ActomyosinHydrogelsActinsCell MovementFibroblastsActinsActomyosinHydrogelsactincell migrationdurotaxisfilopodiamechanosensationmyosinzyxin

Identifiers

PMID36475639
PMCPMC9839609

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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.