Programmable nanomaterials via hybrid assembly of computationally designed coiled coil bundlemers
Date
2020
Authors
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Publisher
University of Delaware
Abstract
Utilization of biomacromolecules to engineer self-assembled materials that display target structure and function at the nanoscale is an active area of new materials research. Peptides that are short sequences of amino acids are excellent candidates for this purpose. Computational prediction of peptide sequences has further enabled faster screening and deterministic design of peptide-based biomaterials. In my dissertation, I discuss the utility of artificial non-natural peptides that were computationally designed to form coiled coils, also called bundlemers. Short, α-helical peptides tetramerize to form a bundlemer with a hydrophobic core and display side chains that are strategically chosen to drive their assembly under mild solution conditions. ☐ Via a feedback cycle between experiments and sequence-optimization algorithms, we have tested multiple peptide designs for successful bundlemer formation. Specifically, small angle neutron scattering (SANS) measurements have confirmed that all bundlemers are robust 2 nm x 4 nm cylinders. I show that these bundlemers exhibit short-range attraction and long-range repulsion (SALR) interactions. Inter-bundlemer interactions are uniquely impacted by sequence-specific surface-charge patterns, making bundlemers excellent globular-protein mimicking patchy colloidal systems. ☐ Taking advantage of their structural robustness, we have modified the bundlemers to incorporate thiol or maleimide groups at the N-termini of the constituent peptides that has yielded tetra-functional ‘monomers’. The decorated bundlemers are reacted via a thiol-Michael click reaction, resulting in end-to-end polymerization of bundlemers. Short linkers between bundlemers yielded rigid rod-like polymers, whereas longer flexible linkers resulted in semi-rigid chain-like polymers, both having a cross-section of ≈ 2 nm (confirmed via SANS) and easily viewed under a Transmission Electron Microscope. The difference in inter-bundlemer dynamics within rigid rod-like versus semi-rigid chain-like polymers has been corroborated by Neutron Spin Echo measurements. ☐ We have shown that due to the step-growth polymerization kinetics of thiol-Michael click reaction, the average length of rigid rod-like polymers is readily tunable. SANS investigation into the inter-rod interactions has confirmed that the rigid rod-like polymers behave as polyelectrolytes in solution while also displaying a large intrinsic persistence length. I also present the results of our investigation into lyotropic liquid crystal formation in concentrated solutions of rigid rod-like polymers that is found to be dependent on constituent bundlemer design. Thus, I show that bundlemer-based rigid rod-like polymers are also excellent model systems to study sequence-driven structure-property relationships in proteinaceous 1-d assemblies.
Description
Keywords
Bundlemer, Click chemistry, Neutron spin echo, Peptides, Self-assembly, Small-angle scattering