An Exploration of Multiple Component Peptide Assemblies by Enzyme‐Instructed Self‐Assembly

Abstract

Based on the motifs (RNISY (M) and DEEVELILGDT (D)) in the protein crystal structures of Merlin and CRL4 DCAFÀ 1 , we phosphorylated the tyrosine residue in M and conjugated M to a self-assembling motif to produce a phosphopeptide (1P) and examined enzyme-instructed self-assembly (EISA) of 1P with and without the presence of D (4). Our results show that EISA of 1P forms a hydrogel at exceedingly low volume fraction (~0.03 %) even with the presence of the hydrophilic peptide, 4. Unlike 1P, 2P (a diastereomer of 1P) or 3P (the enantiomer of 1P) forms a hydrogel via EISA when their concentration is four or three times that of 1P, respectively. Circular dichroism (CD) spectra show that increasing the concentration of the phosphopeptides lowers the CD signals of the mixtures, and the magnitudes of the CD signals depends on the interaction between M and D. This work provides insight for understanding multi-component hydrogels formed by self-assembly, which involves both specific intermolecular interaction and enzymatic reactions.

Designing Pathway-Controlled Multicomponent Ultrashort Peptide Hydrogels with Diverse Functionalities at the Nanoscale for Directing Cellular Behavior

“…Despite displaying diverse structural and physicochemical properties, the biological applications of short-peptide hydrogels based on a single type of gelator molecule is limited due to their weak mechanical properties and lack of chemical as well as functional diversity arising from a single-molecular domain. , An interesting way to enhance the mechanical, structural, and functional characteristics is by nanoengineering a 3D fibrous network through molecular coassembly of two or more functional peptide building blocks. − Coassembly of two or more peptides with surfactants, polymers, or other aromatic peptide amphiphiles having distinct functionalities can result in nanostructures with synergistically combined properties of both the coassembling entities. − In this context, several eminent research groups of Ulijn, Reches, Gazit, and Adler-Abramovich have emphasized that the incorporation of a coassembly approach has resulted in enhanced control over the nanostructures along with the possibility of generating new materials with emergent properties. ,,,,− This approach has led to the formation of superior materials with diverse morphologies and tunable mechanical properties coupled with improved cell–matrix interactions. ,,,,− , Moreover, the application of coassembled hydrogels in drug delivery, wound healing, light harvesting, and in inverting the supramolecular chirality has also been reported. − …”