Role of Symmetry to Dictate Pathway-Driven Self-assembly in Photoresponsive Peptide Amphiphiles

Stimuli-responsive peptides offer interesting structural space in the realm of emergent pathway-driven supramolecular polymerization toward designing functional nanomaterials with precise structure-function characteristics. However, the role of molecular symmetry in such peptides to govern the self-assembly pathway dynamics remains less explored. We design amyloid-inspired, azobenzene-functionalized symmetric (P₁) and asymmetric (P₂) peptide amphiphiles in the E form of the azobenzene motif to systematically investigate the interplay of molecular symmetry, solvent composition, and temperature to guide supramolecular organization. Spectroscopic and microscopic analyses reveal distinct aggregation pathways, with E-P₁ exhibiting rapid nucleation-elongation toward robust and stable nanofibers, while E-P₂ assembles into a kinetic state (E-P₂(KS)) that subsequently transforms into thermodynamically favored nanoribbons, E-P₂(TS), via a "good and bad solvent" modulation strategy. Further, E-P₁ remains structurally resilient due to stronger intermolecular interactions. Interestingly, E-P₂ demonstrates reversible E→Z photoisomerization in both kinetic and thermodynamic states, facilitating supramolecular disassembly while retaining the self-organization memory. Notably, the activation energy barriers for Z→E isomerization in P₂ differ between its kinetic and thermodynamic states, underscoring the role of pathway complexity and molecular symmetry in peptide assembly. These insights advance the understanding of symmetry-regulated supramolecular assembly to modulate the emergent functional properties for potential applications in nanotechnology and biomaterials.