Precision Engineering of Peptoid Nanosheet Lattices to Create 1D Crystalline Nanofibers

A surprisingly large number of polypeptoids, either sequenced-defined or not, are able to form supramolecular assemblies with nearly identical crystalline lattices, where the backbones are extended and aligned directly atop one another. Evidence from direct cryo-TEM imaging, AFM, NMR and X-ray scattering, on many different peptoid nanostructures, further reveal that there is a common conformational motif (referred to as the Sigma strand) where all the backbone amides are in a cis conformation, and adjacent monomers alternate in backbone chirality. This universal structural behavior across many different side chains, enables precision engineering of the peptoid lattice to control nanoscale morphology, and introduce function. Here, we introduce point mutations at specific locations within a peptoid nanosheet crystal lattice to create the pH-dependent formation of nanofibers. These peptoid nanofibers are also crystalline, but are only 1 molecule thick, 2 molecules wide, and hundreds of nanometers long, and yet have a molecular conformation nearly identical to a nanosheet. Insights into the structural basis of this finding by cryo-TEM 3D reconstruction and MD simulation will be discussed.