Evidence map›Paper›PMID 27434669›Full record

ArticleeLife2016

Cooperative unfolding of distinctive mechanoreceptor domains transduces force into signals.

Lining Ju, Yunfeng Chen, Lingzhou Xue, Xiaoping Du, Cheng Zhu

Abstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
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

63 citing papers in PubMed.

  1. Article
  2. Biomechanical anticoagulation by spherical platelets in extracorporeal systems.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Beyond hemostasis, the immunomodulatory nature of platelets.Research and practice in thrombosis and haemostasis · 2025
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. [Molecular dynamics simulation of force-regulated interaction between glycoprotein IbSheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023
    Article
  17. Review
  18. Article
  19. Review
  20. Article

3 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.

Lining JuCoulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States.
Yunfeng ChenPetit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, United States.
Lingzhou XueDepartment of Statistics, The Pennsylvania State University, University Park, United States.
Xiaoping DuDepartment of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, United States.
Cheng ZhuCoulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States.ORCID 0000-0002-1718-565X

Funding

Signaling mechanisms of platelet GPIb-IXR01HL062350 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DU, XIAOPING · 2000 to 2017
$6.0M
Outside-in signaling mechanisms of platelet integrin alpha-llb-beta3R01HL080264 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DU, XIAOPING · 2007 to 2019
$4.6M
Single-platelet analysis of mechano-reception by GPIb alphaR01HL132019 · NHLBI · GEORGIA INSTITUTE OF TECHNOLOGY · PI ZHU, CHENG · 2016 to 2024
$3.8M
New Strategies for Treating Septic Vasculopathy Inflammation and ThrombosisR01HL125356 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI BONINI, MARCELO G., DU, XIAOPING · 2014 to 2018
$3.4M
NHLBI NIH HHS R01 HL062350NHLBI NIH HHS R01 HL080264NHLBI NIH HHS R01 HL125356NHLBI NIH HHS R01 HL132019
6 · The paper itself

Abstract

How cells sense their mechanical environment and transduce forces into biochemical signals is a crucial yet unresolved question in mechanobiology. Platelets use receptor glycoprotein Ib (GPIb), specifically its α subunit (GPIbα), to signal as they tether and translocate on von Willebrand factor (VWF) of injured arterial surfaces against blood flow. Force elicits catch bonds to slow VWF-GPIbα dissociation and unfolds the GPIbα leucine-rich repeat domain (LRRD) and juxtamembrane mechanosensitive domain (MSD). How these mechanical processes trigger biochemical signals remains unknown. Here we analyze these extracellular events and the resulting intracellular Ca(2+) on a single platelet in real time, revealing that LRRD unfolding intensifies Ca(2+) signal whereas MSD unfolding affects the type of Ca(2+) signal. Therefore, LRRD and MSD are analog and digital force transducers, respectively. The >30 nm macroglycopeptide separating the two domains transmits force on the VWF-GPIbα bond (whose lifetime is prolonged by LRRD unfolding) to the MSD to enhance its unfolding, resulting in unfolding cooperativity at an optimal force. These elements may provide design principles for a generic mechanosensory protein machine.

Indexed as

Blood PlateletsCalciumHumansMechanoreceptorsPlatelet Glycoprotein GPIb-IX ComplexProtein BindingProtein Foldingvon Willebrand Factoradhesion receptorCalciumPlatelet Glycoprotein GPIb-IX Complexvon Willebrand Factorbiomembrane force probebiophysicscalcium signalingGPIbhumanleucine rich repeatmechanosensingplateletsingle moleculestructural biologyvon willebrand diseasevon willebrand factorworm like chain

Identifiers

PMID27434669
PMCPMC5021522

What OpenQuestion holds

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Registered trials

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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.