Porous lattice formation through coiled coil peptide nanoparticle assembly driven by natural and non-natural hydrophobic side chains

Abstract

Peptide coiled coil particles, termed ‘bundlemers’, were modified with different hydrophobic side chains strategically positioned at identical locations in their primary sequences, ensuring consistent spatial display on the particle surfaces. Through hydrophobically driven interparticle interactions, these modified bundlemers self-assembled into ordered, crystalline-like porous lattices in aqueous solution. Specifically, both non-natural (furan, alkyne) and natural (phenylalanine, tyrosine, tryptophan) hydrophobic amino acid side chains were studied. While sharing a common parent peptide amino acid sequence and identical modification sites, the new peptide sequences physically assembled into porous lattices that were distinctly different from previously reported lattice assemblies that utilized alloc-functionalized bundlemers. Some of the new lattices displayed identical nanostructure despite having different hydrophobic side chains, while others displayed unique lattice structures, highlighting the subtlety in the interactions between the different hydrophobic side chains. The new porous lattices were characterized using transmission electron microscopy (TEM), cryogenic TEM (cryoTEM), small angle x-ray scattering (SAXS), and computational modeling, including simulations of both lattice structures and dimers of bundlemers. Overall, these results clearly demonstrate the versatility and precision achievable in nanoporous materials design by strategically selecting hydrophobic groups displayed on coiled-coiled bundlemer particles.