Gold Nanosphere-Mediated Morphology Transitions in Hybrid Assemblies of Helical Polypeptides

Abstract Self-assembly of polypeptides provides a versatile platform for constructing biomimetic materials with hierarchical and spatially organized architectures. However, strategies for directing polypeptide assemblies into controllable and discrete bent, curved, or closed structures reminiscent of those observed in higher-order biomacromolecular organization remain limited. Here, we report gold nanosphere (AuNS)-mediated self-assembly of α-helical poly(γ-benzyl-l-glutamate) (PBLG), a synthetic polypeptide that serves as a biomimetic rod-like building block. We show that thiol-functionalized PBLG coassembles with AuNSs to form curved horseshoe-like intermediates and closed toroidal structures, whereas unfunctionalized PBLG exhibits no association with AuNSs and retains cylindrical architectures. The resulting morphology of the hybrid co-assembly is governed by AuNS size and loading, as well as PBLG chain length and secondary structure, highlighting the cooperative roles of molecular architecture and nanoscale compatibility in controlling supramolecular organization. Cryo-transmission electron microscopy and circular dichroism spectroscopy suggest that AuNS incorporation generates local packing frustration within the anisotropic PBLG assemblies, thereby promoting progressive bending and, under appropriate conditions, toroid closure. These findings establish end-group-mediated nanoparticle incorporation as a simple strategy for controlling curvature in synthetic polypeptide assemblies, providing a foundation for exploring hybrid architectures for cargo delivery and DNA polycatenane-inspired hierarchical assemblies.