TEMPLATE INDUCED ASSEMBLY AND SEQUENTIAL GROWTH: NEW MECHANISMS FOR THE GROWTH OF BUNDLEMER NANORODS AND BRUSHES

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Proteins are incredibly complex materials. These sequence-defined polymers are capable of assembling intro incredibly specific nanostructures through a complicated interplay of physical and covalent interactions. Due to a combination of the large combinatoric space and redundancies amongst the 20 natural amino acids, complete de novo design of fully folded proteins to form specific 3d structures is not fully realized. While the de novo design of proteins is currently out of reach, it is possible to computationally design new smaller polypeptides based on well understood protein folding motifs. One of these motifs, the coiled coil, is particularly well suited for computational design. Bundlemers are a series of computationally designed coiled coil forming peptides that fold into approximately 2nm x 4nm cylindrical nanoparticles in water. By adding click chemistry functional groups to the N-termini of the bundlemers, it has been previously shown that they can be used as monomers in a A-A B-B step growth like polymerization. The resulting bundlemer nanorods show extremely high aspect ratios and remarkable stiffness. In my dissertation, I studied new methods for producing high stiffness bundlemer nanorods and developed new methods to bind bundlemers to inorganic substrates. I expanded on the “bundlemers as monomers” approach by developing two new synthesis pathways, sequential growth and template induced assembly. Sequential growth forms macromolecular grafting-from bundlemer brushes by growing bundlemer nanorods from a surface, one bundlemer addition at a time. Studying this approach on colloidal gold nanoparticles, I grew monodisperse bundlemer brushes with high grafting densities and well-defined quantized lengths based on the number of bundlemer additions. Expanding this work to include flat substrates, I found that the grafting density of single layer bundlemer brushes was heavily dependent on the electrostatic interactions between bundlemers and that neutrally charged bundlemers had denser grafting compared with more highly charged bundlemers in the same solution conditions. Template induced assembly takes a different approach to bundlemer nanorod growth. Instead of using two folded and stable bundlemer building blocks, template induced assembly used a folded polypeptide bundlemer as a structural template to induce coiled coil formation in a disordered oligopeptide computationally designed to form a coiled coil. When the disordered oligopeptide was conjugated to the N-terminus of the template bundlemer, it quickly folded into an anti-parallel homotetrameric coiled coil, driving supramolecular polymerization into bundlemer nanorods. Both step-growth and template induced bundlemer nanorods formed large continuous α-helices based on their CD spectra and formed high stiffness nanorods based on TEM.
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