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Sci Rep. 2017 Feb 10;7:42119. doi: 10.1038/srep42119.

Localization of Short-Chain Polyphosphate Enhances its Ability to Clot Flowing Blood Plasma.

Author information

1
Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
2
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
3
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
4
Department of Chemical Engineering, University of Illinois at Chicago, Chicago, IL, USA.
5
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.

Abstract

Short-chain polyphosphate (polyP) is released from platelets upon platelet activation, but it is not clear if it contributes to thrombosis. PolyP has increased propensity to clot blood with increased polymer length and when localized onto particles, but it is unknown whether spatial localization of short-chain polyP can accelerate clotting of flowing blood. Here, numerical simulations predicted the effect of localization of polyP on clotting under flow, and this was tested in vitro using microfluidics. Synthetic polyP was more effective at triggering clotting of flowing blood plasma when localized on a surface than when solubilized in solution or when localized as nanoparticles, accelerating clotting at 10-200 fold lower concentrations, particularly at low to sub-physiological shear rates typical of where thrombosis occurs in large veins or valves. Thus, sub-micromolar concentrations of short-chain polyP can accelerate clotting of flowing blood plasma under flow at low to sub-physiological shear rates. However, a physiological mechanism for the localization of polyP to platelet or vascular surfaces remains unknown.

PMID:
28186112
PMCID:
PMC5301195
DOI:
10.1038/srep42119
[Indexed for MEDLINE]
Free PMC Article

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