Abstract
The blood-clotting protein von Willebrand factor (vWF) can be activated by small molecules, high shear stress, and interactions with interfaces. It subsequently binds platelet receptor glycoprotein Ibα (GPIbα) at the surface of platelets, thereby playing a crucial role in blood clotting due to platelet activation, which is an important process to consider in the design of cardiovascular implants and biomaterials used in blood-contacting applications. The influence of surfaces on the activation and the molecular-level structure of surface-bound vWF is largely unknown. Recent studies have indicated that when bound to hydrophobic polystyrene (PS), the A1 domain of vWF remains accessible for GPIbα binding. However, the detailed secondary structure and exact orientation of vWF A1 at the PS surface is still unresolved. Here, the authors resolve these features by studying the system with sum-frequency generation (SFG) spectroscopy. The data are consistent with a scenario where vWF A1 maintains a native secondary structure when bound to PS. Comparison of experimental and calculated SFG spectra combined with previously reported time-of-flight secondary ion mass spectrometry data suggests that A1 assumes an orientation with the GPIbα binding domain oriented away from the solid surface and exposed to the solution phase. This structural information will benefit future in vitro experiments with surface-adsorbed A1 domain and may have relevance for the design of novel blood-contacting biomaterials and wound-healing applications.