Evidence map›Paper›PMID 29343646›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Role of boundary conditions in determining cell alignment in response to stretch.

Kellen Chen, Andrea Vigliotti, Mattia Bacca, Robert M McMeeking, Vikram S Deshpande, Jeffrey W Holmes

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
5.9field-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

65 citing papers in PubMed, 125 citations in OpenAlex.

  1. Article
  2. A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026
    Review
  3. Cyclic stretch inhibits cell invasion in 3D scaffolds.bioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Endothelial-specific CXCL12 regulates neovascularization during tissue repair and tumor progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  14. Article
  15. ALKBH5-mediated mClinical and translational medicine · 2024
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

5 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

6 authors at 4 institutions in 3 countries.

Kellen ChenDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
Andrea VigliottiDepartment of Engineering, University of Cambridge, CB2 1PZ Cambridge, United Kingdom.
Mattia BaccaDepartment of Mechanical Engineering, University of California, Santa Barbara, CA 93106.
Robert M McMeekingDepartment of Mechanical Engineering, University of California, Santa Barbara, CA 93106.
Vikram S DeshpandeDepartment of Engineering, University of Cambridge, CB2 1PZ Cambridge, United Kingdom.
Jeffrey W HolmesDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908; holmes@virginia.edu.
University of California, Santa Barbara · USUniversity of Virginia · USInnova (Italy) · ITUniversity of Cambridge · GB

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008715 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LAURIE, GORDON WILLIAM · 2000 to 2019
$6.6M
NIGMS NIH HHS T32 GM008715
6 · The paper itself

Abstract

The ability of cells to orient in response to mechanical stimuli is essential to embryonic development, cell migration, mechanotransduction, and other critical physiologic functions in a range of organs. Endothelial cells, fibroblasts, mesenchymal stem cells, and osteoblasts all orient perpendicular to an applied cyclic stretch when plated on stretchable elastic substrates, suggesting a common underlying mechanism. However, many of these same cells orient parallel to stretch in vivo and in 3D culture, and a compelling explanation for the different orientation responses in 2D and 3D has remained elusive. Here, we conducted a series of experiments designed specifically to test the hypothesis that differences in strains transverse to the primary loading direction give rise to the different alignment patterns observed in 2D and 3D cyclic stretch experiments ("strain avoidance"). We found that, in static or low-frequency stretch conditions, cell alignment in fibroblast-populated collagen gels correlated with the presence or absence of a restraining boundary condition rather than with compaction strains. Cyclic stretch could induce perpendicular alignment in 3D culture but only at frequencies an order of magnitude greater than reported to induce perpendicular alignment in 2D. We modified a published model of stress fiber dynamics and were able to reproduce our experimental findings across all conditions tested as well as published data from 2D cyclic stretch experiments. These experimental and model results suggest an explanation for the apparently contradictory alignment responses of cells subjected to cyclic stretch on 2D membranes and in 3D gels.

Indexed as

Cell Physiological PhenomenaAnimalsBiomechanical PhenomenaCells, CulturedCollagenFibroblastsGelsImaging, Three-DimensionalModels, BiologicalRatsStress, MechanicalCollagenGelscell mechanicscomputational modelingcytoskeletonfibroblast orientationstress fibers

Identifiers

PMID29343646
PMCPMC5798351
OpenAlexW2783083211

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.