Evidence map›Paper›PMID 31069336›Full record

ArticleAPL bioengineering2019

Matrix crosslinking enhances macrophage adhesion, migration, and inflammatory activation.

Jessica Y Hsieh, Mark T Keating, Tim D Smith, Vijaykumar S Meli, Elliot L Botvinick, Wendy F Liu

Open access · goldAbstract read
In one paragraph

Article in APL bioengineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. PIEZO1 in Immune Cells: From Force to Function.Results and problems in cell differentiation · 2026
    Review
  4. Review
  5. Review
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  7. Article
  8. Article
  9. Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. 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

6 authors at 1 institution in 1 country.

Jessica Y HsiehDepartment of Biomedical Engineering and The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, California 92697, USA.
Mark T KeatingDepartment of Biomedical Engineering and The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, California 92697, USA.
Tim D SmithDepartment of Biomedical Engineering and The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, California 92697, USA.ORCID https://orcid.org/0000-0002-5750-0706
Vijaykumar S MeliDepartment of Biomedical Engineering and The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, California 92697, USA.
Elliot L BotvinickDepartment of Biomedical Engineering and The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, California 92697, USA.
Wendy F LiuDepartment of Biomedical Engineering and The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine, Irvine, California 92697, USA.ORCID https://orcid.org/0000-0002-8904-7643
University of California, Irvine · US

Funding

Engineering Biomaterials to Exert Molecular Control of Immune Cell FunctionDP2DE023319 · NIDCR · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, WENDY · 2012 to 2012
$2.3M
Training Program in Cardiovascular Applied Research and EntrepreneurshipT32HL116270 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUGHES, CHRISTOPHER C. W. · 2013 to 2022
$1.6M
Mechanochemical regulation of macrophages by the extracellular matrix during wound healingR21AI128519 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, WENDY · 2017 to 2018
$405k
NHLBI NIH HHS T32 HL116270NIAID NIH HHS R21 AI128519NIDCR NIH HHS DP2 DE023319
6 · The paper itself

Abstract

Macrophages are versatile cells of the innate immune system that can adopt a variety of functional phenotypes depending on signals in their environment. In previous work, we found that culture of macrophages on fibrin, the provisional extracellular matrix protein, inhibits their inflammatory activation when compared to cells cultured on polystyrene surfaces. Here, we sought to investigate the role of matrix stiffness in the regulation of macrophage activity by manipulating the mechanical properties of fibrin. We utilize a photo-initiated crosslinking method to introduce dityrosine crosslinks to a fibrin gel and confirm an increase in gel stiffness through active microrheology. We observe that matrix crosslinking elicits distinct changes in macrophage morphology, integrin expression, migration, and inflammatory activation. Macrophages cultured on a stiffer substrate exhibit greater cell spreading and expression of αM integrin. Furthermore, macrophages cultured on crosslinked fibrin exhibit increased motility. Finally, culture of macrophages on photo-crosslinked fibrin enhances their inflammatory activation compared to unmodified fibrin, suggesting that matrix crosslinking regulates the functional activation of macrophages. These findings provide insight into how the physical properties of the extracellular matrix might control macrophage behavior during inflammation and wound healing.

Identifiers

PMID31069336
PMCPMC6481736
OpenAlexW2923149190

What OpenQuestion 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 OpenQuestion graph.