Architectural control of rod-coil block polypeptide thermoresponsive self-assembly <i>via de novo</i> design of coiled-coil orientation

The architectural control of the self-assembly of a series of block polypeptides comprising a concatenation of an elastin-like peptide and a coiled-coil, bundle-forming peptide (ELP-BFPs), has been demonstrated. Assembly of the polypeptides is controlled by coacervation of the hydrophobic ELP domain, while the type of coiled-coil assembly of the BFP and the specific placement of short histidine tags significantly tunes assembly behavior. Spectrophotometric analysis of self-assembly demonstrated that the transition temperature of assembly can be controlled by the design of the BFP domain and positioning of the His-tags in the constructs. Cryogenic transmission electron microscopy of assembled polypeptides confirmed distinct morphologies including core-shell particles and multilayer vesicles, depending on the parallel or antiparallel bundle architecture of the block polypeptide. The results have applications in materials design and highlight the potential for controlling multi-stimuli responsiveness and morphologies through fine control of the architectural features of the component polypeptide domains.