title: Localization of Short-Chain Polyphosphate Enhances its Ability to Clot Flowing Blood Plasma.
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.
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ju Hun
authors.initials: JH
authors.lastname: Yeon
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Nima
authors.initials: N
authors.lastname: Mazinani
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
authors.forename: Travis S
authors.initials: TS
authors.lastname: Schlappi
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Karen Y T
authors.initials: KY
authors.lastname: Chan
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: James R
authors.initials: JR
authors.lastname: Baylis
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Donovan
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
authors.forename: Damien
authors.initials: D
authors.lastname: Kudela
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
authors.forename: Galen D
authors.initials: GD
authors.lastname: Stucky
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Morrissey
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000378:metabolism; D002478:Cells, Cultured; D003198:Computer Simulation; D006801:Humans; D044085:Microfluidics / Q000295:instrumentation; D008955:Models, Cardiovascular; D053758:Nanoparticles / Q000737:chemistry*; D015539:Platelet Activation; D011122:Polyphosphates / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties; D013917:Thrombin / Q000737:chemistry / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood* / Q000139:chemically induced; D014914:Whole Blood Coagulation Time
chemical_list: D011122:Polyphosphates; D013917:Thrombin