Instant Hydrogelation Inspired by Inflammasomes

Based on the recent near-atomic structures of the PYRIN domain of ASC in the protein filament of inflammasomes and the observation that the active form of vitamin B6 (pyridoxal phosphate, P5P) modulates the self-assembly of ASC, we rationally designed an N-terminal capped nonapeptide (Nap-FFKKFKLKL, 1) to form supramolecular nanofibers consisting of α-helix. The addition of P5P to the solution of 1 results in a hydrogel almost instantly (about 4 seconds). Several other endogenous small molecules (for example, pyridoxal, folinic acid, ATP, and AMP) also convert the solution of 1 into a hydrogel. As the demonstration of correlating assemblies of peptides and the relevant protein epitopes, this work illustrates a bioinspired approach to develop supramolecular structures modulated by endogenous small molecules.