Computational and Experimental Identifications of Hierarchical Peptoid Self-Assembly Pathways*

Rational design of self-assembling nanomaterials is predicated on the fundamental understandings of their atomic-level assembly pathways. Here, we conduct an integrated computational and experimental investigation of the hierarchical self-assembly pathways of short amphiphilic peptoids. Peptoids are a class of highly tailorable synthetic peptidomics polymers, which can be engineered to assemble into various hierarchical nanostructures including spheres, helices, tubes, and sheets. For a particular peptoid design, we resolve the critical stages in the peptoid assembly pathway using molecular dynamics calculations that we corroborate by experimental measurements. Our results support an assembly mechanism by which monomers first assemble into disordered cylindrical aggregates that self-orders into a helix, and that multiple helices aggregate and unravel into crystalline sheets. This new understanding of the hierarchical peptoid assembly pathways provides guidance for the future rational design of peptoid-based nanomaterials.