Evidence map›Paper›PMID 22659883›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012

Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness.

Aleksandar Marinković, Justin D Mih, Jin-Ah Park, Fei Liu, Daniel J Tschumperlin

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

97 citing papers in PubMed, 151 citations in OpenAlex.

  1. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2015
    Trial
  2. Matrices of physiologic stiffness potently inactivate idiopathic pulmonary fibrosis fibroblasts.American journal of respiratory cell and molecular biology · 2013
    Trial
  3. Article
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  5. Article
  6. Article
  7. Physiomimetic culture bias durotaxis toward soft environments.bioRxiv : the preprint server for biology · 2026
    Article
  8. Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026
    Review
  9. The importance of mechanical forces in chronic respiratory diseases.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Field Guide to Traction Force Microscopy.Cellular and molecular bioengineering · 2024
    Review
  17. Review
  18. Review
  19. Article
  20. Article

37 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Aleksandar MarinkovićMolecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Justin D Mih
Jin-Ah Park
Fei Liu
Daniel J Tschumperlin
Department of Physiological Sciences · RU

Funding

Training Program in Molecular and Integrative Physiological SciencesT32HL007118 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI LU, QUAN · 1985 to 2025
$14.3M
Mechanobiology of Lung FibrosisR01HL092961 · NHLBI · MAYO CLINIC ROCHESTER · PI Daniel J. Tschumperlin · 2009 to 2026
$8.0M
NHLBI NIH HHS R01HL092961NHLBI NIH HHS T32HL007118
6 · The paper itself

Abstract

Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-β1 (TGF-β1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-β1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-β1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation.

Indexed as

Cells, CulturedExtracellular MatrixFetusFibroblastsFluorescent Antibody TechniqueHumansLungMicroscopyPhosphorylationPulmonary FibrosisSignal TransductionSmad2 ProteinSmad3 ProteinTractionTransforming Growth Factor betaSmad2 ProteinSMAD2 protein, humanSmad3 ProteinTransforming Growth Factor beta

Identifiers

PMID22659883
PMCPMC3423859
OpenAlexW2120736394

What OpenQuestion holds

Textmetadata
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.