Peptides that oligomerize into robust coiled coils have emerged as promising candidates for constructing self-assembled nanomaterials that display designed, hierarchical organization of the coiled coil bundles. Using an optimized computational prediction algorithm, artificial coiled coils that consist of four identical α-helical peptides were designed such that the 30 amino acid peptides pack in an antiparallel fashion within the individual coiled coil bundle. Chemical modification of the peptide N-termini to incorporate an extra cysteine or maleimide functional group resulted in coiled coil bundles decorated with either four thiols or four maleimide moieties (two at either bundle end due to antiparallel peptide packing within bundles). These modified bundles were subsequently covalently linked together using different linker types via Thiol-Michael <i>click</i> reactions to build polymers of coiled coils, or “bundlemers”, that were readily viewable under the Transmission Electron Microscope (TEM). Specifically, a short rigid linker between bundles resulted in formation of rigid rods of coiled coils displaying a persistence length greater than tens of microns while a flexible linker between bundles resulted in semiflexible fibers with a shorter persistence length. Also, via computational design, the net charge on the bundle-forming peptides was altered (-8 to +8) such that the resulting bundlemers carried different net charge densities and local charge patchiness. The differences in the assembled nanostructures driven by peptide sequence manipulation are encoded in their respective Small-Angle Neutron Scattering or X-ray Scattering (SANS, SAXS) curves which further confirmed the success of the computational design strategy and hybrid assembly pathway. Furthermore, concentrated solution of rigid rods displayed liquid crystallinity wherein the birefringent texture was responsive to the presence of sodium chloride salt, which indicates an electrostatically-driven interaction and assembly of the coiled-coil based rigid rods in solution. This result is supported by scattering of the rod solutions under different solution conditions, and we show that such inter-rod interactions are readily tunable by sequence manipulation of the coiled coil forming peptides.

Rigid rod vs semiflexible chain construction through connection of computationally designed coiled coil peptides using Thiol-Michael <i>click</i> reaction

2019 Spring National Meeting

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Rigid rod vs semiflexible chain construction through connection of computationally designed coiled coil peptides using Thiol-Michael click reaction