Electrostatic intermolecular co-assembly of coiled coil peptide bundles into well-defined nanostructures

Abstract

Molecular self-assembly provides a powerful bottom-up approach for the creation of structured, tailored nanomaterials. Among various intermolecular interactions, polyelectrolyte complexation, driven by electrostatic interactions between oppositely charged macromolecules, is a particularly versatile strategy for designing new materials with diverse properties. This thesis explores the use of computationally designed, highly charged coiled-coil peptide bundles, termed 'bundlemers', as programmable building blocks for constructing novel polyelectrolyte complexes and ordered materials. ☐ The research presented herein began with the design and synthesis of a library of tunable, highly charged peptide bundlemers. These bundlemers were designed to possess a single type of charge and a well-defined, rigid, cylinder-like morphology. The first in-depth investigation included herein is the co-assembly of oppositely charged, single-charge peptide bundlemers through electrostatic interactions. Structural characterization using transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) confirmed the formation of two-dimensional (2D) porous peptide lattices. The morphology of these lattices, including transitions from rectangular to diamond-like shapes, and the lattice symmetry was controlled by modulation of the charge stoichiometry, the spatial arrangement of charged residues on the bundlemer surfaces, and the chemical functionality of the charged amino acid side chains. ☐ Building upon this, the second study included deals with the complexation of charged peptide bundlemers with oppositely charged, flexible polyelectrolytes. This investigation revealed a spectrum of material phases, from liquid-like coacervates to ordered solid complexes. It was found that the size of the coacervate droplets could be controlled by the length of the polypeptides. Remarkably, single-charge bundlemers were also shown to template flexible macromolecules into highly ordered solid structures, including hexagonal patterns with polypeptides and body-centered cubic (BCC) packing with oligonucleotides. These findings provided fundamental insights into the sequence-structure-property relationships that govern polyelectrolyte complexation. ☐ Finally, to expand the functional repertoire of these materials, elastin-like polypeptides (ELPs) were incorporated into the bundlemer architecture. The introduction of this thermoresponsive domain allowed environmental control over the self-assembly process. It was demonstrated that the thermoresponsive assembly of these ELP-bundlemer conjugates could be directed to form distinct morphologies, such as particles or multilayer micelles, by the specific design of the ELP block and the bundlemer. Furthermore, the incorporation of metal-coordination sites into the ELP-bundlemer system provided an additional handle to direct the assembly into defined one-dimensional (1D) structures. This work established a versatile and programmable platform for the de novo design of functional nanomaterials with precise control over their structure and properties with the uniqueness of the bundlemer particle highlighted throughout.