Evidence map›Paper›PMID 25246564›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Platelet mechanosensing of substrate stiffness during clot formation mediates adhesion, spreading, and activation.

Yongzhi Qiu, Ashley C Brown, David R Myers, Yumiko Sakurai, Robert G Mannino, Reginald Tran, Byungwook Ahn, Elaissa T Hardy, Matthew F Kee, Sanjay Kumar and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
8.5field-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

117 citing papers in PubMed, 209 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Platelet effector functions in inflammation.Research and practice in thrombosis and haemostasis · 2026
    Review
  5. Review
  6. Fibrin as a Versatile Fibrous Biopolymer.Sub-cellular biochemistry · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

57 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

13 authors at 2 institutions in 1 country.

Yongzhi QiuWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322;
Ashley C BrownWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332;
David R MyersWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322;
Yumiko SakuraiWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322;
Robert G ManninoWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322;
Reginald TranWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322;
Byungwook AhnWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322;
Elaissa T HardyWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322;
Matthew F KeeWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332;
Sanjay KumarDepartment of Bioengineering, University of California, Berkeley, CA 94720; and.
Gang BaoWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
Thomas H BarkerWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.ORCID http://orcid.org/0000-0002-3218-8111
Wilbur A LamWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute of Emory University, Atlanta, GA 30322; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332 wilbur.lam@emory.edu.
Georgia Institute of Technology · USUniversity of California, Berkeley · US

Funding

Nanomedicine Center for Nucleoprotein MachinesPN2EY018244 · NEI · RICE UNIVERSITY · PI BAO, GANG · 2006 to 2015
$24.4M
Translational Research SkillsU54HL112309 · NHLBI · EMORY UNIVERSITY · PI LOLLAR, JOHN S. · 2012 to 2016
$12.1M
Endothelialized microfluidics for sickle cell disease research & drug discoveryR01HL121264 · NHLBI · EMORY UNIVERSITY · PI LAM, WILBUR A · 2014 to 2018
$2.0M
NEI NIH HHS PN2 EY018244NEI NIH HHS PN2EY018244NHLBI NIH HHS R01 HL121264NHLBI NIH HHS R01HL121264NHLBI NIH HHS U54 HL112309NHLBI NIH HHS U54HL112309
6 · The paper itself

Abstract

As platelets aggregate and activate at the site of vascular injury to stem bleeding, they are subjected to a myriad of biochemical and biophysical signals and cues. As clot formation ensues, platelets interact with polymerizing fibrin scaffolds, exposing platelets to a large range of mechanical microenvironments. Here, we show for the first time (to our knowledge) that platelets, which are anucleate cellular fragments, sense microenvironmental mechanical properties, such as substrate stiffness, and transduce those cues into differential biological signals. Specifically, as platelets mechanosense the stiffness of the underlying fibrin/fibrinogen substrate, increasing substrate stiffness leads to increased platelet adhesion and spreading. Importantly, adhesion on stiffer substrates also leads to higher levels of platelet activation, as measured by integrin αIIbβ3 activation, α-granule secretion, and procoagulant activity. Mechanistically, we determined that Rac1 and actomyosin activity mediate substrate stiffness-dependent platelet adhesion, spreading, and activation to different degrees. This capability of platelets to mechanosense microenvironmental cues in a growing thrombus or hemostatic plug and then mechanotransduce those cues into differential levels of platelet adhesion, spreading, and activation provides biophysical insight into the underlying mechanisms of platelet aggregation and platelet activation heterogeneity during thrombus formation.

Indexed as

Acrylic ResinsBlood CoagulationBlood PlateletsCell MovementCellular MicroenvironmentFibrinFibrinogenHumansImmobilized ProteinsMechanotransduction, CellularMicroscopy, ConfocalPhosphatidylserinesPlatelet ActivationPlatelet AdhesivenessPlatelet AggregationPlatelet Glycoprotein GPIIb-IIIa ComplexAcrylic ResinsFibrinFibrinogenImmobilized ProteinsPhosphatidylserinesPlatelet Glycoprotein GPIIb-IIIa ComplexPolyacrylamidesP-Selectinrac1 GTP-Binding Proteinbiomaterialscell mechanicsmechanotransductionplatelet cytoskeleton

Identifiers

PMID25246564
PMCPMC4210024
OpenAlexW2097503680

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.