Surface-Induced Hydrogelation Inhibits Platelet Aggregation

Abstract

We demonstrate that a tripeptide hydrogelator, Nap-FFG, can selectively self-assemble at the surface of platelets, thus inhibiting ADP-, collagen-, thrombin- and arachidonic acid (AA)-induced human platelet aggregations with the IC(50) values of 0.035 (41), 0.14 (162), 0.062 (68), and 0.13 mg/mL (148 μM), respectively. Other tripeptide hydrogelators with chemical structures of Nap-FFX (X = A, K, S, or E) could not or possessed less potencies to inhibit platelet aggregations. We observed higher amounts of Nap-FFG at the platelet surface by the techniques of LC-MS and confocal microscopy. We also observed self-assembled nanofibers around the platelet incubated with the Nap-FFG by cryo-TEM. The ζ potential of Nap-FFG treated platelets was a little bit more negative than that of untreated ones. The amount of Nap-FFG at the surface of NIH 3T3 cells was much less than that of platelets. These observations suggested that Nap-FFG could selectively self-assemble through unknown ligand-receptor interactions and form thin layers of hydrogels at the surface of platelets, thus preventing the aggregation of them. This study not only broadened the application and opened up a new door for biomedical applications of molecular hydrogels but also might provide a novel strategy to counteract infection diseases through selective surface-induced hydrogelations at pathogens, such as bacteria and virus.