How crystallographic orientation-induced fibrinogen conformation affects platelet adhesion and activation on TiO 2 .

Control of protein adsorption is essential for successful integration of healthcare materials into the body. Since human plasma fibrinogen (HPF) is one of the most thrombogenic proteins, its conformation is a key upstream regulator for platelet behavior, and thus pathological clot formation at the blood-biomaterial interface. Our previous study revealed that the conformation of adsorbed HPF can be controlled by rutile surface crystallographic orientation. Therefore, we hypothesized that pre-adsorbed HPF on specific rutile orientation can regulate platelets adhesion and activation. Here, we show that platelets exposed to the four low index (110), (100), (101), (001) facets of TiO 2 (rutile) exhibit surface-specific behavior. SEM observations of platelets morphology and P-selectin expression measurement revealed that on (110) facets, platelets adhesion and activation was suppressed. In contrast, extensive surface coverage by fully activated platelets was observed on (001) facets. Platelet's behavior has been linked to the conformation of the HPF and thereby availability of platelet-binding sequences. AFM imaging supported by immunochemical analysis showed that on (110) facets, HPF is adsorbed in trinodular conformation rendering the γ400-411 platelet-binding sequence inaccessible. Our research has potential implications on the bioactivity of different materials crystal facets, reducing the risk of pathological clot formation and thromboembolic complications. This article is protected by copyright. All rights reserved.