Using a Kinase/Phosphatase Switch to Regulate a Supramolecular Hydrogel and Forming the Supramolecular Hydrogel in Vivo

We have designed and synthesized a new hydrogelator Nap−FFGEY (1), which forms a supramolecular hydrogel. A kinase/phosphatase switch is used to control the phosphorylation and dephosphorylation of the hydrogelator and to regulate the formation of supramolecular hydrogels. Adding a kinase to the hydrogel induces a gel−sol phase transition in the presence of adenosine triphosphates (ATP) because the tyrosine residue is converted into tyrosine phosphate by the kinase to give a more hydrophilic molecule of Nap−FFGEY−P(O)(OH)2 (2); treating the resulting solution with a phosphatase transforms 2 back to 1 and restores the hydrogel. Electron micrographs of the hydrogels indicate that 1 self-assembles into nanofibers. Subcutaneous injection of 2 in mice shows that 80.5 ± 1.2% of 2 turns into 1 and results in the formation of the supramolecular hydrogel of 1 in vivo. This simple biomimetic approach for regulating the states of supramolecular hydrogels promises a new way to design and construct biomaterials.