Photochemically Sequestered Off-Pathway Dormant States of Peptide Amphiphiles for Predictive On-Demand Piezoresponsive Nanostructures

Abstract

Supramolecular assemblies are essential for specific biological functions and mandate precise control over the mesoscopic scale for higher functional efficiency. Such well-defined biomimetic self-organization can be accessed through kinetically controlled nonequilibrium transformations rather than the typical downhill thermodynamically driven processes. Recently, spatiotemporal control for the living supramolecular polymerization has rendered a paradigm shift toward designing complex multicomponent supramolecular active materials; however, directing the active monomer toward predictive kinetically trapped materials still remains a considerable challenge as this necessitates circumventing spontaneous nucleation of the monomers during the self-assembly process. Herein, we demonstrate dual strategies (chemical and photo) to sequester the active peptide self-assembling motifs in dormant states that, upon judicious activation, engage in controlled seeded supramolecular polymerization in aqueous milieu for the first time. Amyloid-inspired peptide 1 with a pendant azobenzene moiety demonstrates the formation of on-pathway metastable nanoparticles by the interplay of solvent and temperature that could be transformed into kinetically controlled nanofibers and thermodynamically controlled twisted bundles. Further, using coupled equilibrium such as the host–guest inclusion complex with cyclodextrin or photoisomerization with UV light leads to the formation of two distinct off-pathway metastable states that retard the spontaneous supramolecular polymerization. A judicious manipulation of the free-energy landscapes in tandem with suitable chemical and photostimuli renders the activation of the dormant states for the peptide self-assembly through a seeded growth strategy. Finally, such photochemical sequestration of self-assembly pathways results in on–off piezoresponsive peptide nanostructures. In summary, we demonstrated for the first time the nonequilibrium peptide self-assembly coupled with dormant metastable states to allow access to an interesting repertoire of structural diversities and attenuated piezoresponse control in supramolecular peptide nanostructures.