title: Surface-dependent expression in the platelet GPIb binding domain within human von Willebrand factor studied by atomic force microscopy.
abstract: Adsorption of plasma proteins such as von Willebrand factor (vWF) on thrombogenic surfaces can induce conformational changes in tertiary structure so that the prothrombotic functional epitopes are exposed for interactions with platelets, resulting in platelet adhesion and thrombus formation. Thus, understanding platelet binding following changes in the structure of vWF is critical in understanding the mechanisms of thrombogenesis. The present study examined the accessibility of platelet binding epitopes within vWF adsorbed on two different thrombogenic surfaces, a hydrophobic synthetic surface and collagen VI coated substrates, under physiological buffer conditions using atomic force microscopy (AFM) in combination with immunogold labeling. Our results demonstrated that the glycoprotein Ib (GPIb) binding domain in vWF undergoes changes when adsorbed on collagen VI compared to vWF on a hydrophobic synthetic surface. This study provides a basis for a novel approach to understand the molecular mechanisms of surface-induced thrombosis by directly examining the structure-function relationships of plasma proteins involved in the thrombus formation.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Wickenden Room 303, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Kang
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Raghavachari
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hofmann
authors.forename: Roger E
authors.initials: RE
authors.lastname: Marchant
mesh_terms: D000327:Adsorption; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D024142:Collagen Type VI / Q000737:chemistry; D000939:Epitopes; D006801:Humans; D007150:Immunohistochemistry; D018625:Microscopy, Atomic Force; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012821:Silanes / Q000737:chemistry; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013927:Thrombosis / Q000209:etiology; D014841:von Willebrand Factor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D024142:Collagen Type VI; D000939:Epitopes; D019038:Platelet Glycoprotein GPIb-IX Complex; D012821:Silanes; D014841:von Willebrand Factor