Work

Spacer Length as a Molecular Cue for Self‐Sorting, Living Growth, and Piezoresponse in Peptide Assemblies

Year: 2026

Type: article

Abstract: Supramolecular polymerization offers a powerful route to structurally precise and functionally complex materials; however, achieving controlled multicomponent assembly and emergent functionality remains a fundamental challenge. In this study, we show that minimal variations in methylene spacer length between bisurea motifs encode the self-assembly behavior of peptide amphiphiles. Cy3- and Cy5-labeled peptides undergo nucleation-elongation-driven assembly into nanofibers with spacer-dependent secondary structures. FRET and super-resolution microscopy reveal that identical spacers promote random co-assembly, whereas even a single methylene mismatch induces high-fidelity self-sorting. Pre-formed fibers exhibit negligible monomer exchange, indicating nonequilibrium assemblies. Leveraging this, seeded supramolecular polymerization affords well-defined block copolymers with low dispersity and spatially resolved domains. Furthermore, spacer length and odd-even parity modulate dipolar alignment, enabling spacer length-dependent piezoresponse. Collectively, these findings demonstrate how subtle molecular design parameters act as a molecular cue to program multicomponent supramolecular polymerization, offering new opportunities for designing compartmentalized, functional biomaterials and supramolecular bioelectronic systems.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.4984465