title: 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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Lijie
authors.initials: L
authors.lastname: Song
authors.forename: Chongyi
authors.initials: C
authors.lastname: Chen
authors.forename: Di
authors.initials: D
authors.lastname: Guan
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Li
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Yang
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D020100:Hydrogels; D009842:Oligopeptides