Evidence map›Paper›PMID 35657074›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022

Stiffening Matrix Induces Age-Mediated Microvascular Phenotype Through Increased Cell Contractility and Destabilization of Adherens Junctions.

Rahel Schnellmann, Dimitris Ntekoumes, Mohammad Ikbal Choudhury, Sean Sun, Zhao Wei, Sharon Gerecht

Open access · goldAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
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

29 citing papers in PubMed, 42 citations in OpenAlex.

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  6. Matrix stiffness induces endothelial network senescence.bioRxiv : the preprint server for biology · 2025
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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

6 authors at 1 institution in 1 country.

Rahel SchnellmannDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Dimitris NtekoumesDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Mohammad Ikbal ChoudhuryThe Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
Sean SunThe Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
Zhao WeiDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Sharon GerechtDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-8542-4835
Johns Hopkins University · US

Funding

The Role of Physical Cues in Collective Cell InvasionU54CA210173 · NCI · JOHNS HOPKINS UNIVERSITY · PI GERECHT, SHARON · 2016 to 2020
$9.9M
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
Air Force FA9550-20-1-0356Maryland Stem Cell Research Fund MSCRFF-5159National Science Foundation ECCS-2025064NCI NIH HHS U54 CA210173NCI NIH HHS U54 CA210173-01NIGMS NIH HHS R01 GM134542Translational Research Institute through NASA Cooperative NNX16AO69ATranslational Research Institute through NASA Cooperative RAD0102
6 · The paper itself

Abstract

Aging is a major risk factor in microvascular dysfunction and disease development, but the underlying mechanism remains largely unknown. As a result, age-mediated changes in the mechanical properties of tissue collagen have gained interest as drivers of endothelial cell (EC) dysfunction. 3D culture models that mimic age-mediated changes in the microvasculature can facilitate mechanistic understanding. A fibrillar hydrogel capable of changing its stiffness after forming microvascular networks is established. This hydrogel model is used to form vascular networks from induced pluripotent stem cells under soft conditions that mimic young tissue mechanics. Then matrix stiffness is gradually increased, thus exposing the vascular networks to the aging-mimicry process in vitro. It is found that upon dynamic matrix stiffening, EC contractility is increased, resulting in the activation of focal adhesion kinase and subsequent dissociation of β-catenin from VE-Cadherin mediated adherens junctions, leading to the abruption of the vascular networks. Inhibiting cell contractility impedes the dissociation of β-catenin, thereby preventing the deconstruction of adherens junctions, thus partially rescuing the age-mediated vascular phenotype. The findings provide the first direct evidence of matrix's dynamic mechano-changes in compromising microvasculature with aging and highlight the importance of hydrogel systems to study tissue-level changes with aging in basic and translational studies.

Indexed as

Adherens Junctionsbeta CateninEndothelial CellsHydrogelsPhenotypebeta CateninHydrogelscollagendisease modelextracellular matrix mechanicshydrogelinduced pluripotent stem cellsvascular aging

Identifiers

PMID35657074
PMCPMC9353494
OpenAlexW4281761023

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.