Evidence map›Paper›PMID 28831047›Full record

ArticleNature communications2017

Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

Hongxia Fu, Yan Jiang, Darren Yang, Friedrich Scheiflinger, Wesley P Wong, Timothy A Springer

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. 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
11.3field-weighted citation impact, top 1% 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, 203 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Hongxia FuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-6893-8260
Yan JiangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-2745-4323
Darren YangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-2271-6910
Friedrich ScheiflingerShire, Vienna, 1220, Austria.
Wesley P WongProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA. Wesley.Wong@childzrens.harvard.edu.ORCID http://orcid.org/0000-0001-7398-546X
Timothy A SpringerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA. Springer_lab@crystal.harvard.edu.ORCID http://orcid.org/0000-0001-6627-2904
Boston Children's Hospital · US

Funding

Structures of Alpha 4 Integrins, Ligands and AntagonistsP01HL103526 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI SPRINGER, TIMOTHY A · 2011 to 2015
$11.1M
Mechanical forces in nanoscale biology: From hemostasis to single-molecule centrifugationR35GM119537 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI Wesley Philip Wong · 2016 to 2026
$5.2M
Single molecule measurements on von Willebrand factor A1 and A2 domainsR01HL108248 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI SPRINGER, TIMOTHY A · 2011 to 2015
$2.4M
Total Internal Reflection Fluorescence MicroscopeS10RR026549 · NCRR · HARVARD MEDICAL SCHOOL · PI DANUSER, GAUDENZ · 2010 to 2010
$311k
NCRR NIH HHS S10 RR026549NHLBI NIH HHS P01 HL103526NHLBI NIH HHS R01 HL108248NIGMS NIH HHS R35 GM119537
6 · The paper itself

Abstract

Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

Indexed as

HemostasisAlgorithmsHemorrhageHumansHydrodynamicsKineticsMicrofluidicsModels, MolecularPlatelet Glycoprotein GPIb-IX ComplexProtein BindingProtein Conformationvon Willebrand Factoradhesion receptorPlatelet Glycoprotein GPIb-IX Complexvon Willebrand Factor

Identifiers

PMID28831047
PMCPMC5567343
OpenAlexW2748786452

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.