The complexity of multi-component molecular assembly demands precise control strategies to enhance both efficiency and selectivity. Heterogeneous nucleation and the autocatalytic secondary pathway, as key regulatory strategies, have attracted widespread attention for their crucial roles in crystal growth and amyloid protein aggregation. Here, we apply a heterogeneous nucleation strategy to supramolecular polymer systems and report the first direct observation of surface-enrichment-induced primary nucleation and a spontaneous fragmentation-driven autocatalytic secondary process. A heterogeneous nucleating agent promotes primary nucleation, facilitating supramolecular chiral induction. The resulting chiral polymers undergo a catalytic cycle of fragmentation and re-growth at their termini, with the fragments also acting as seeds for nucleation and growth. These pathways play a crucial role in the polymerization process and are essential for chiral transfer and asymmetry amplification, enabling the achievement of maximum enantioselectivity with as little as 0.5% molar equivalent of the heterogeneous nucleating agent. Furthermore, we reveal the existence of an optimal equivalent in their catalytic kinetics, arising from a surface assembly mechanism. In this mechanism, monomers adsorbed on the surface of the heterogeneous nucleating agent assemble with those in solution, rather than through surface diffusion and assembly. This process resembles the surface-catalyzed Eley–Rideal mechanism. Our study highlights the potential of heterogeneous nucleation as an effective strategy for controlling supramolecular polymerization and offers new insights into its underlying mechanism.

The assembly of peptides is generally mediated by liquid–liquid phase separation, which enables control over assembly kinetics, final structure, and functions of peptide-based supramolecular materials. Modulating phase separation can alter the assembly kinetics of peptides by changing solvents or introducing external fields. Herein, we demonstrate that the assembly of peptides can be effectively catalyzed by complex coacervates. The negatively charged sodium alginate (SA) can form complex coacervates with the positively charged KLVFFAE (Aβ16–22, abbreviated as KE) peptide, thereby lowering the nucleation barrier and promoting the assembly of the peptide. As the binding affinity of SA-KE and the dosage of SA decrease, the system shifts from a relatively inefficient template-induced assembly to a highly efficient catalytic assembly before ultimately reverting to slow spontaneous assembly. Therefore, both the affinity as well as the stoichiometry do not follow the intuitive rule that “more is better”, but rather there exists an optimal value that maximizes the rate of assembly.