Programming Supramolecular Polymerization Pathways through Aromatic Mutation and Photoresponsive Switching

Abstract

Precise control over supramolecular polymerization pathways remains a central challenge for peptide-based materials. Here, we demonstrate that minimal structural mutation via the systematic deletion of aromatic residues provides a powerful handle to program pathway complexity and functional outcomes in photoresponsive peptide assemblies. A series of azobenzene-tethered peptide bolaamphiphiles (P1–P3) were designed to modulate aromatic interactions and thereby tune the kinetic and thermodynamic landscape of self-assembly. The E-isomers of P1 and P2 undergo cooperative nucleation–elongation polymerization with E -P1 and E -P2 proceeding via parallel and serial (saturating) pathways, respectively, to furnish nanofibers, while E -P3 forms disordered nanoparticles. Variable-temperature studies reveal rate-dependent access to various aggregated states. Accordingly, both E -P1 and E -P2 exhibit pathway-dependent self-assembly, with the thermal annealing rate and molecular design dictating access to distinct supramolecular states. Kelvin probe force microscopy (KPFM) correlates these structural states with tunable surface potentials arising from differences in dipolar alignment owing to the differential packing of the peptide molecules, supported by theoretical analysis highlighting the role of aromatic interactions. E/Z photoisomerization modulates supramolecular organization in a solvent- and structure-dependent manner, with the Z-isomer of P3 furnishing one-dimensional nanofibers via an isodesmic pathway, demonstrating light-triggered self-assembly. Seeded polymerization further confirms living supramolecular growth by bypassing the nucleation barriers. These findings establish a direct relationship between molecular design, intermolecular aromatic interactions, and pathway-dependent supramolecular organization in photoresponsive peptide assemblies.