Structural Superimposition

Abstact

Structural complexity in biological matter arises from molecular information that encodes supramolecular assembly across length scales(1-3). Here we show that minimal nine-residue peptides can encode discrete lateral interaction motifs that direct supramolecular organization. These motifs generate hexagonal pores and hierarchically tile into multichannel nanofibrils with defined topology. Sequence-encoded amphiphilicity combines a cross-beta-dimer, an inversion point and a trimeric junction to create complementary interfaces that couple lateral growth to axial stacking, yielding honeycomb lattices with continuous approximately 5-nm solvent-accessible nanochannels. Cryo-electron microscopy resolves the supramolecular architecture and shows that lattice symmetry and pore geometry are preserved across variants. Systematic perturbations establish sequence-structure rules linking residue position to supramolecular symmetry, lattice propagation and channel topology. Molecular dynamics simulations and vibrational spectroscopy show that the channels remain water accessible and show sequence-tunable hydration. These findings establish that a minimal, sequence-encoded interaction hierarchy can programme long-range supramolecular order, providing a general framework for how short peptides can encode complex, symmetry-defined architectures(4-12).