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Thromb Haemost 2007; 97(04): 514-526
DOI: 10.1160/TH06-05-0274
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Soluble plasma-derived von Willebrand factor assembles to a haemostatically active filamentous network

Alexej Barg
1   Institute of Physiology II – Nanolab
,
Rainer Ossig
2   Institute of Physiological Chemistry and Pathobiochemistry
,
Tobias Goerge
3   Department of Dermatology, University Hospital of Muenster, Muenster, Germany
4   Currently: CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachussetts, USA
,
Matthias F. Schneider
5   Biological Physics Group, University of Augsburg, Augsburg, Germany
,
Hermann Schillers
1   Institute of Physiology II – Nanolab
,
Hans Oberleithner
1   Institute of Physiology II – Nanolab
,
Stefan W. Schneider
3   Department of Dermatology, University Hospital of Muenster, Muenster, Germany
› Author Affiliations
Further Information

Publication History

Received 17 May 2006

Accepted after resubmission 08 February 2007

Publication Date:
24 November 2017 (online)

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Summary

The large glycoprotein vonWillebrand factor (VWF) is involved in the initial haemostatic reaction mediating the interaction between platelets and the injured vessel wall. It has been demonstrated that unusually large VWF (ULVWF) multimers after being released from endothelium are capable of developing elongated membrane-anchored strings that are hyperactive to bind platelets. In the present study we investigated whether soluble plasma-derived VWF is competent to develop similar thrombotically active multimers. We demonstrated that soluble VWF multimers isolated from human plasma self-assemble to a network of fibers immobilized on a collagen matrix and are functionally active to bind platelets. Formation of these VWF fibers depends on shear flow, concentration of solubleVWF, and a suitable binding surface. Self-assembly of soluble VWF does not require the presence of cellular membrane ligands. The network of fibers is subjected to rapid degradation by proteolytic activity of plasma ADAMTS-13.Atomic force microscopy images elucidate the nanostructure of VWF fibers and illustrate self-association and -aggregation of several filamentous multimers. Together, these results suggest that circulatingVWF can contribute to a formation of hyperactive VWF fibers on exposed subendothelial collagen during vascular injury.

Keywords

ULVWF multimers - platelet adhesion - atomic force microscopy - soluble VWF
 

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