## 1 Introduction  
Platelet interaction with subendothelial collagen is a crucial step in hemostasis or arterial thrombosis after vascular injury or rupture of an atherosclerotic plaque, respectively [1,2]. In blood flowing with high shear rates, the initial capture of platelets is mediated by the von Willebrand factor (VWF), which avidly binds to collagens and is a ligand for the glycoprotein (GP) complex GPIb-V-IX [3]. The two platelet collagen receptors integrin \(\alpha_{2}\beta_{1}\) and GPVI ensure stable platelet adhesion and mediate platelet activation [4,5]. For over 20 years, GPVI has been recognized as the central signaling collagen receptor on platelets [6,7]. Studies using genetically modified mice have shown that the (patho)physiological process of arterial thrombus formation can be approximated using microfluidics devices, in which whole blood is perfused over a collagen surface [8]. The collagen fibers immobilized in such devices, for instance those applied as microspots, also bind plasma VWF and thus promote shear-dependent adhesion, activation, and aggregation of platelets [3,9]. Previous results have revealed a strong interplay of GPIb-V-IX, GPVI, and integrin \(\alpha_{2}\beta_{1}\) in the formation of large and stable multilayered thrombi in a way where the two other receptors enforce the GPVI-induced activation of platelets [10,11]. Markedly, the thrombi that formed on collagen fibers appeared to be heterogeneous in structure, with on the one hand patches of aggregated platelets with activated integrin \(\alpha_{\text{III}}\beta_{3}\) binding fibrinogen and CD62P expression via \(\alpha\)-granule secretion and on the other hand single procoagulant platelets, exposing phosphatidylserine (PS), which is required for coagulation factor binding [12]. Particularly active in supporting thrombus formation is the standard collagen preparation \"Horm\" (collagen-H), which is a fibrillar type I collagen prepared in a proprietary process that is commonly used for diagnostics in the clinical laboratory. Still unexplained is why other fibril-forming type I and III collagen preparations, also binding with VWF, are less active in supporting thrombus formation under flow [9,13]. In previous years, a number of synthetic collagen-derived triple-helical peptides have been identified that, similarly to collagen-H, bind to GPVI and/or integrin \(\alpha_{2}\beta_{1}\) and thus induce platelet adhesion and activation in vitro [10]. Peptides containing the (GPO)\({}_{\text{n}}\) motif, in contrast to the supposedly inactive (GPP)\({}_{\text{n}}\) motif, bind to GPVI, while peptides with the GFOGER motif act as strong ligands for integrin \(\alpha_{2}\beta_{1}\)[14, 15, 16]. The prototypes of such triple-helical peptides are the cross-linked collagen-related peptide (CRP-XL) with a (GPO)\({}_{10}\) sequence, which hence acts as a potent GPVI agonist, and the combined GFOGER-(GPO)\({}_{\text{n}}\) sequence, which binds to platelets via both receptors. Subtle changes in the GFOGER sequence have been found to alter the affinity for \(\alpha_{2}\beta_{1}\). For instance, the substitution of phenylalanine in GFOGER by alanine in GAOGER resulted in lower-affinity \(\alpha_{2}\beta_{1}\) binding and in diminished platelet adhesion under static conditions [17]. Platelet activation through GPVI [18, 19, 20], but not via GPIb-V-IX [21], relies on a potent protein tyrosine kinase cascade, culminating in the activation of the tyrosine kinase Syk. This GPVI signaling pathway involves phosphorylation of the Fc receptor \(\gamma\)-chain via Src-family kinases and construction of a GPVI signalosome, in which Syk phosphorylates and activates phospholipase C (PLC)-\(\gamma\)2, causing a rise in the central second messenger, Ca\({}^{2+}\)[18, 22, 23, 24]. However, the relative importance of this pathway has not been investigated thus far in platelets interacting under flow with surface-immobilized collagen peptides or fibrillar collagens.