Poster abstracts

Poster number 16 submitted by Jeffrey Tonniges

Regulation of Collagen Fiber Structure and Platelet-Collagen Interactions by DDR1

Jeff Tonniges (Biophysics Graduate Program, The Ohio State University), Ben Albert (Biomedical Engineering Department, The Ohio State University), Edward Calomeni (Department of Pathology, The Ohio State University), Gunjan Agarwal (Biomedical Engineering Department, The Ohio State University)

Abstract:
Collagen fibers, a major component of the extracellular matrix of blood vessels, confer structural and mechanical integrity to the vessel wall. At sites of vascular injury, collagen is exposed to flowing blood, and von Willebrand factor (VWF) and platelet collagen receptor, GPVI, initiate platelet adhesion by binding to the exposed collagen. The native structure of collagen fibers is critical for platelet adhesion. The assembly of collagen fibers is regulated by collagen-binding proteins like discoidin domain receptor 1 (DDR1). Few studies have investigated how alteration in the fiber structure modulates platelet-collagen interactions. This study aimed to determine how DDR1 changes the morphology of collagen fibers in-vivo, and how these changes altered GPVI- and VWF-collagen interactions. To investigate this, mouse aortas from DDR1 KO and WT littermates were isolated and cut into cross-sections. The ultrastructure of collagen fibers was examined by transmission electron microscopy and atomic force microscopy. VWF and GPVI binding to collagen in the vessel wall was determined by incubating aortic sections with recombinant GPVI or platelet-poor plasma and examining protein binding by immunofluorescence. Collagen in the adventitia of DDR1 KO aortas exhibited a reduced width of D-periodicity and an increased depth of D-periodicity. DDR1 KO aortas exhibited greater VWF binding than WT, while no difference was observed for GPVI binding. These studies will elucidate a novel mechanism, namely how changes in the collagen fiber structure modulate platelet-collagen interactions. Based on our results, a down-regulation of DDR1 in the vessel wall could be considered as a biomarker for cardiovascular pathologies prone to thrombogenic events.

Keywords: collagen, platelets, vascular biology