title: Shear-Dependent Interactions of von Willebrand Factor with Factor VIII and Protease ADAMTS 13 Demonstrated at a Single Molecule Level by Atomic Force Microscopy.
abstract: Vital functions of mammals are only possible due to the behavior of blood to coagulate most efficiently in vessels with particularly high wall shear rates. This is caused by the functional changes of the von Willebrand Factor (VWF), which mediates coagulation of blood platelets (primary hemostasis) especially when it is stretched under shear stress. Our data show that shear stretching also affects other functions of VWF: Using a customized device to simulate shear conditions and to conserve the VWF molecules in their unstable, elongated conformation, we visualize at single molecule level by AFM that VWF is preferentially cleaved by the protease ADAMTS13 at higher shear rates. In contrast to this high shear-rate-selective behavior, VWF binds FVIII more effectively only below a critical shear rate of ∼30.000 s(-1), indicating that under harsh shear conditions FVIII is released from its carrier protein. This may be required to facilitate delivery of FVIII locally to promote secondary hemostasis.
authors.affiliation: Institute of Chemical Technologies and Analytics, Vienna University of Technology , Getreidemarkt 9/164, A-1060 Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bonazza
authors.affiliation: Baxalta Innovations, Industriestrasse 67, A-1221 Vienna, Austria.
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Rottensteiner
authors.affiliation: Baxalta Innovations, Industriestrasse 67, A-1221 Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schrenk
authors.affiliation: Central Machine Shop of the Faculty Technical Chemistry, Vienna University of Technology , Getreidemarkt 9/174, A-1060 Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Frank
authors.affiliation: Institute of Chemical Technologies and Analytics, Vienna University of Technology , Getreidemarkt 9/164, A-1060 Vienna, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Allmaier
authors.affiliation: Baxalta Innovations, Industriestrasse 67, A-1221 Vienna, Austria.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Turecek
authors.affiliation: Baxalta Innovations, Industriestrasse 67, A-1221 Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
authors.affiliation: Institute of Chemical Technologies and Analytics, Vienna University of Technology , Getreidemarkt 9/164, A-1060 Vienna, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Friedbacher
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D000071120:ADAMTS13 Protein; D005169:Factor VIII / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D018625:Microscopy, Atomic Force; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D014841:von Willebrand Factor / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D011994:Recombinant Proteins; D014841:von Willebrand Factor; D005169:Factor VIII; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human