Designed coiled-coil peptide nanoparticles with tunable self-assembly: distinct ordered nanostructures <i>via</i> nonnatural side chain modification and electrostatic screening

Peptide 'bundlemers' are homotetrameric coiled-coils that form discrete cylindrical nanoparticles in aqueous solution. The stability of the coiled-coil design enables selective modification of exterior residues to program interparticle interactions. We designed a single charge-type (SC) bundlemer, containing only positive ionizable groups on its exterior, with allyloxycarbonyl (alloc)-protected lysine positioned to direct hydrophobic interparticle assembly. SC bundlemers with no alloc functionalization form liquid crystalline phases through end-to-end stacking of nanoparticles into chains that are laterally repulsive due to electrostatic interactions. Incorporation of alloc groups into the SC design yielded different, ordered nanostructures depending on solution conditions. Nematic and hexagonal columnar liquid crystals were formed in pure water, where end-to-end particle stacking and lateral repulsion dominated. In contrast, ordered nanoporous lattices were formed in the presence of salt, where electrostatic screening revealed alloc-driven, lateral hydrophobic interactions coupled with particle end-to-end stacking. Uniquely, the lattices exhibited structure factor signatures identical to those of the previously observed in alloc-modified mixed charge bundlemers, highlighting how precise, protein-like spatial display of desired chemical functionality enables targeted interparticle interactions and tunable nanostructure formation.