Abstract
Von Willebrand factor (VWF) is a large multimeric adhesive glycoprotein, with complex roles in thrombosis and hemostasis, present in circulating blood and in secretory granules of endothelial cells and platelets. High shear stress triggers conformational changes responsible for both binding to the platelet receptor glycoprotein GpIb and its self-association, thus supporting the formation of platelet plug under flow. Ristocetin also promotes the interaction of VWF with GpIb and is able to induce platelet aggregation, and thus is largely used to mimic this effect in vitro. In this research paper, we followed the time course of VWF self-association in solution induced by ristocetin binding by light scattering and at the same time we collected atomic force microscopy images to clarify the nature of the assembly that is formed. In fact, this process evolves initially through the formation of fibrils that subsequently interact to form supramolecular structures whose dimensions would be capable of trapping platelets even in the absence of any degree of shear stress or interaction with external surfaces. This intrinsic property, that is the ability to self-aggregate, may be involved in some pathological settings that have been revealed in clinical practice.
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Acknowledgments
R.D.C. acknowledges the financial support provided by MIUR (PRIN-2007) and the generous provision of some of the reagents used in this study by Grifols Italia (Ghezzano, Pisa, Italy). M.D.S., G.A., A.A., E.D.S., and R.D.C. were also supported by the funds assigned to the research programs D.1 2006 and 2007 of the Medicine Faculty of Università Cattolica del S. Cuore, Rome, Italy. Experimental data reported in this paper were obtained at the LABCEMI (Laboratorio Centralizzato di Microscopia, Ottica ed Elettronica) of the Università Cattolica del S. Cuore Roma (Italy). (http://webprd.rm.unicatt.it/pls/unicatt_rm/consultazione.mostra_pagina?id_pagina=20215).
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Papi, M., Maulucci, G., De Spirito, M. et al. Ristocetin-induced self-aggregation of von Willebrand factor. Eur Biophys J 39, 1597–1603 (2010). https://doi.org/10.1007/s00249-010-0617-8
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DOI: https://doi.org/10.1007/s00249-010-0617-8