From Coacervates to Ordered Lattices: Sequence‐Guided Condensation of Polyelectrolyte Complexes Through Designed Coiled‐Coil Peptides

Electrostatic complexation of oppositely charged biomacromolecules produces a spectrum of condensed phases, from liquid coacervates to ordered solids. Yet the underlying amino acid sequence‐level rules remain poorly understood. Here, we utilize computationally designed coiled‐coil peptide “bundlemers” as a programmable platform to systematically investigate these principles. This study demonstrates that precise control over the material phase formed through electrostatic complexation is achieved through subtle amino acid sequence modifications. By tuning coiled coil terminal motifs and surface charge distribution, bundlemer‐polypeptide complexation can span liquid coacervates, soft solids, or solid precipitates. Specifically, bundlemer coiled coil nanoparticles with +24 charge were complexed with different lengths of polyanionic polypeptide. Nanoparticles with a mixed charge character containing both acidic and basic amino acids produced coacervate phases. When the bundlemers displayed only basic amino acids making a single charge‐type +24 nanoparticle, solid precipitates with specific hexagonal lattice symmetry were formed. When the charge character was flipped with negatively charged bundlemers and positively charged polypeptide, similar hexagonally packed complexes were formed. This work establishes a robust framework for programming the self‐assembly of polyelectrolyte‐based soft matter, offering a sequence‐guided pathway from disordered liquid condensates to precisely defined, ordered nanomaterials.