Charge Directed Selective Co‐Assembly of Ionic Complementary Peptide Binary Mixtures

Multicomponent peptide nanostructures offer a powerful platform for designing functional materials, yet controlling their co-assembly remains a key challenge. Here, we harness electrostatic molecular recognition to drive the selective co-assembly of five amphiphilic ionic peptide binary mixtures (M₁-M₅). Our results revealed that charge distribution governs β-sheet strand alignment (parallel vs. antiparallel), assembly kinetics, and hydrogel viscoelasticity. Mixing stoichiometry and pH significantly influences co-assembly behavior, nanofiber morphology, and network structure (self-sorted vs. hetero-aggregated). At pH 7, equimolar mixtures undergo nucleation-driven co-assembly into hetero-aggregates, immediately forming well-defined nanofibers, while non-equimolar ratios yield altered morphologies. At a slightly acidic pH of 5-7, both E and K side chains are charged, enabling complementary ionic interactions that promote co-assembly and gelation. Outside this pH range, co-assembly is impaired. Notably, M₁ forms β-sheets and hydrogels at acidic pH (≤4) via independent self-assembly of its components, suggesting self-sorted fibers. Overall, we demonstrate that tuning charge complementarity, ionization state, and stoichiometry enables precise control over the molecular, nanoscale, and mechanical properties of multicomponent peptide assemblies, providing a framework for the rational design of advanced peptide-based materials.