Fibronectin binding to von Willebrand factor occurs via the A1 domain. Issue 5 (5th June 2021)

• Record Type: Journal Article
• Authors: Keesler, Daniel A.; Slobodianuk, Tricia L.; Kochelek, Caroline E.; Skaer, Chad W.; Haberichter, Sandra L.; Flood, Veronica H.
• Is Part Of: Research and practice in thrombosis and haemostasis. Volume 5:Issue 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-05
• Subjects: collagen -- extracellular matrix -- fibronectins -- hemostasis -- von Willebrand factor; Thrombosis -- Periodicals; Hemostasis -- Periodicals; 616.135005
• DOI: 10.1002/rth2.12534
• Languages: English
• ISSNs: 2475-0379

Abstract

Abstract: Background: Collagen interactions with von Willebrand factor (VWF) perform an important role in initiation of hemostasis. Objectives: We hypothesized that in addition to collagen, other extracellular matrix (ECM) proteins such as fibronectin can bind VWF. Methods: Fibronectin‐VWF interactions were measured by ELISA using both plasma‐derived and recombinant VWF–containing variants in specific domains. Inhibition was measured by antibody competition using antibodies directed against both VWF and fibronectin. Binding affinities were measured by the Octet Biosensor for fibronectin and collagen IV. Results: Fibronectin was able to bind both plasma‐derived and recombinant wild‐type VWF. This interaction was inhibited by both anti‐VWF antibodies and collagen types III and IV. Several VWF A1 domain variants in the region of the collagen IV binding site also demonstrated absent fibronectin binding, as did variants with defects in high‐molecular‐weight multimers. Binding affinity testing showed fibronectin has a strong affinity for VWF, in a range similar to that of collagen IV. Fibronectin binds VWF via a restricted region of the A1 domain. This interaction requires high‐molecular‐weight multimers and is similar to that seen with vascular collagens. Conclusions: Therefore, VWF would appear to be the common factor linking platelet adhesion to various ECM proteins and facilitating hemostasis under conditions of ECM exposure. Abstract :