Photochemically Sequestered Off-Pathway Dormant States ofPeptide Amphiphiles for Predictive On-Demand PiezoresponsiveNanostructures

Supramolecular assemblies are essential for specific biologicalfunctions and mandate precise control over the mesoscopic scale for higherfunctional efficiency. Such well-defined biomimetic self-organization can beaccessed through kinetically controlled nonequilibrium transformationsrather than the typical downhill thermodynamically driven processes.Recently, spatiotemporal control for the living supramolecular polymer-ization has rendered a paradigm shift toward designing complex multi-component supramolecular active materials; however, directing the activemonomer toward predictive kinetically trapped materials still remains aconsiderable challenge as this necessitates circumventing spontaneousnucleation of the monomers during the self-assembly process. Herein, wedemonstrate dual strategies (chemical and photo) to sequester the activepeptide self-assembling motifs in dormant states that, upon judicious activation, engage in controlled seeded supramolecularpolymerization in aqueous milieu for thefirst time. Amyloid-inspired peptide1with a pendant azobenzene moiety demonstrates theformation of on-pathway metastable nanoparticles by the interplay of solvent and temperature that could be transformed intokinetically controlled nanofibers and thermodynamically controlled twisted bundles. Further, using coupled equilibrium such as thehost-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-energylandscapes 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-offpiezoresponsive peptide nanostructures. In summary, we demonstrated for thefirst time the nonequilibrium peptide self-assemblycoupled with dormant metastable states to allow access to an interesting repertoire of structural diversities and attenuatedpiezoresponse control in supramolecular peptide nanostructures.

Automated summary

In this research, the active peptide self-assembly motifs are sequestered using chemical and photo strategies, and controlled seeded supramolecular polymerization is achieved upon activation. The results show that the amyloid-inspired peptide with a pendant azobenzene can form metastable nanoparticles under the influence of solvent and temperature, which can be transformed into kinetically controlled nanofibers and thermodynamically controlled twisted bundles. Using host-guest inclusion complex or photoisomerization leads to the formation of off-pathway metastable states that retard spontaneous supramolecular polymerization.