Triggering Supramolecular Hydrogelation Using a Protein-Peptide Coassembly Approach.

Abstract

In recent years, the molecular self-assembly approach has witnessed a sudden surge in coassembly strategy to achieve extensive control over accessing diverse nanostructures and functions. To this direction, peptide-peptide coassembly has been explored to some extent in the literature, but protein-peptide coassembly is still in its infancy for controlling the self-assembling properties. To the best of our knowledge, our study illustrated the merits of protein-peptide coassembly toward inducing gelation to a nongelator dipeptide sequence, for the first time. This simplistic approach could provide access to diverse mechanical and structural properties within a single gelator domain at identical concentrations with a simple variation in the protein concentrations. Interestingly, the protein-peptide interactions could transform aggregate-like structures into fibrillar nanostructures. The study attempts to provide the proof of concept for the nonspecific protein-peptide interactions purely based on simple noncovalent interactions. The range of dissociation constants and binding energies obtained from bioloyer interferometry and docking studies confirmed the involvement of noncovalent interactions in protein-peptide coassembly, which triggers gelation. Moreover, different binding affinities of a protein toward an individual peptide essentially demonstrated a route to achieve precise control over differential self-assembling properties. Another important aspect of this study was entrapment of an enzyme protein within the gel network during coassembly without inhibiting enzyme activity, which can serve as a scaffold for catalytic reactions. The present study highlights the nonconventional way of protein-peptide interactions in triggering self-assembly in a nonassembling precursor. We anticipate that fundamental insights into the intermolecular interactions would lead to novel binary supramolecular hydrogels that can be developed as a next generation biomaterial for various biomedical applications.