Bio-Inspired Chain Capping Selectively Inhibits Elongation to Direct Secondary Pathways in Supramolecular Polymers

Amyloid β aggregation in Alzheimer's disease proceeds via fibril elongation and toxic oligomer generation through secondary nucleation. In biology, molecular chaperones selectively modulate these competing pathways to control aggregate formation and toxicity. Replicating such pathway selectivity in synthetic supramolecular polymerization─differentiating elongation from secondary nucleation─remains a major challenge. Here, we introduce a unique bioinspired small-molecule based inhibition strategy that achieves selective modulation of these pathways in seeded supramolecular polymerization. The rationally designed capper selectively binds fibril ends, suppressing elongation via the end-capping mechanism while preserving fibril surfaces for secondary nucleation. This redirects monomer flux from elongation to surface-catalyzed nucleation, dramatically enhancing branching and yielding hierarchical superstructures. In contrast to conventional seeded polymerization, which yields linear architectures dominated by elongation, this tunable kinetic switch establishes a synthetic analogue of chaperone-mediated regulation, providing a general framework for programming pathway selection in supramolecular polymerization to access complex hierarchical materials.