Poster abstracts

Poster number 31 submitted by Jeff Tonniges

Regulation of platelet-collagen interactions by the collagen receptor DDR1

Jeff Tonniges (Biophysics, The Ohio State University), James Jin (College of Medicine, Wexner Medical Center), David Yeung (Biomedical Engineering, The Ohio State University), Shuvro Roy (Biology, The Ohio State University), Edward Calomeni (Renal Pathology and Electron Microscopy Lab, Wexner Medical Center), Gunjan Agarwal (Biomedical Engineering, 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. We have shown earlier that the assembly of collagen fibers in vitro is regulated by the discoidin domain receptors (DDR1 and DDR2) [1, 2]. Recently it was shown that the DDR1 binding site on collagen overlaps with the binding site for von Willebrand Factor (VWF)[3]. VWF binding to collagen serves as a major mechanisms for platelet adhesion to collagen[4]. To determine how DDR1 regulates platelet-collagen interactions, this study employed two aims: (1) determine how DDR1-deficiency affects collagen fiber structure, and (2) determine how binding of DDR1 to collagen affect platelet-collagen interaction. Mouse aortas were isolated from 2 month old female DDR1-/- mice and their wildtype (WT) littermates. The structure of the arterial vessel wall was determined by histology and collagen structure was determined by transmission electron microscopy. Platelet-collagen interactions were determined using platelet or whole blood impedance aggregometry. The collagen structure within both the tunica media and tunica adventitia of DDR1-/- mice had larger fiber diameters and a more heterogeneous distribution than their WT littermates. Whole blood aggregation was inhibited by a collagen fiber and DDR1 mixture. Additionally, collagen polymerized in the presence of DDR1 failed to induce platelet aggregation. While these changes in collagen structure can impact the structure and mechanical properties of the vessel wall, we provide an additional functional significance of expression of DDR1 in the vessel wall. DDR1 could regulate the platelet reactivity of collagen fibers by (1) modulating the collagen fiber structure and thus binding site accessibility, or (2) directly competing for binding sites.

References:
[1] Blissett, A.R., et al. J Mol Bio, 2009, 385, 902-911
[2] Flynn, L.A., et al. J Mol Bio, 2010, 395, 533-43
[3] Xu, H., et al. Matrix Bio, 2011, 30, 16-26
[4] Varga-Szabo, D., et al. Arterioscl Throm Vas, 2008, 28, 403-12

Keywords: collagen, platelets