Designing Amphiphilic Peptoids for Controlling the Formation of Nanostructured Biomimetic Materials

Abstract

Biomacromolecules such as proteins and peptides achieve remarkable functionality through precise molecular sequences, enabling sophisticated folding and hierarchical assembly. However, their complexity and sensitivity in folding and assembly raise significant challenges for molecular design and limit broader applications. Peptoids, or poly-N-substituted glycines, are a versatile class of peptide mimetics that mimic the sequence tunability while offering unique advantages, including resistance to degradation, environmental stability, and ease of synthesis. With programmable sequences with diverse side-chain chemistries, peptoids enable precise control over molecular interactions and self-assembly pathways, making them ideal for studying and engineering biomimetic nanostructures. These characteristics bridge the gap between biological systems and synthetic materials, providing a robust platform for rational design and predictive synthesis of functional materials. This dissertation focuses on the design and self-assembly of amphiphilic peptoids into nanostructured biomimetic materials, with three fundamental areas of investigation. First, we introduce chiral motifs to guide the assembly of short peptoids into nanohelices, revealing how molecular interactions can be tailored to control structural geometry and handedness. Second, we establish how the assembly of amphiphilic peptoids with anisotropic hydrophobic domains can control morphologies between nanosheets, nanotubes, and nanohelices, developing mechanistic insights into assembly polymorphism. Finally, we expand the complexity of peptoid sequences by introducing multiblock architectures, demonstrating their ability to fold and assemble into hierarchical nanosheets while mimicking protein-like folding behavior. Together, these studies provide a comprehensive framework for understanding peptoid assembly and pave the way for rationally designing bioinspired nanostructured materials with applications like catalysis, sensing, and energy storage.