Terminal-Directed Supramolecular Liquid Crystal Formation by Designed Coiled-Coil Interparticle Stacking

Elucidation of the sequence-level dynamics that direct the hierarchical assembly of peptides remains a challenge. Herein, a simulation-guided experimental framework demonstrates that computationally designed, single charge-type (SC), coiled-coil peptides exhibit multiple lyotropic liquid-crystalline (LC) phases via programmable, robust, nonionic, end-to-end stacking. This macroscopic phase behavior is encoded directly in the molecular interaction among terminal residues of the coiled-coil constituent peptides. Specifically, the conformational flexibility of the N-terminus and attractive interactions at the C-terminus promote end-to-end stacking between adjacent coiled coils, providing a lever for fine-tuning of interfacial interactions and, thus, the critical LC-forming concentration (CLC). The phase behavior of SC particles is presented with variation of added salt as well as peptide particle concentration, revealing a rich lyotropic behavior spanning nematic, hexagonal columnar, smectic A, and smectic B phases. Harnessing the molecular control over the stacked interface, tryptophan-mediated cross-linking at the terminal residues was performed, which significantly enhanced the mechanical properties of the liquid crystal system. These findings establish a clear strategy for encoding macroscopic material properties at the molecular level, offering a versatile blueprint for future <i>de novo</i> peptide design with coiled-coil building blocks.