Advisor(s)
Fengbin Wang
Committee Member(s)
Ho-Wook Jun
Peter Prevelige
Terje Dokland
Yabing Chen
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Biochemistry and Molecular Genetics
Date of Award
9-11-2025
Abstract
In biology, nanostructures are composed of small building blocks, including the amino acids that make up proteins, lipids that assemble to form cellular membranes, and nucleic acids that make up our DNA. These higher-order structures perform countless functions that protect us from disease, produce barriers that enable homeostasis in cells, and provide blueprints for molecular factories to synthesize new proteins and other biomolecules. The spontaneous self-assembly of these building blocks produces various hierarchical structures, a process that has invigorated the fields of biomedicine, biotechnology, and materials science. In particular, the rational design of self-assembling peptides (SAPs) has been extensively explored for the purpose of constructing functional nanomaterials (NMs). Materials are typically designed by either a “top-down” approach, where a material is extracted from a larger source, or a “bottom-up” approach, where the material is produced additively from smaller subunits. This holds true at the nanoscale, where individual amino acids—both standard and non-standard—can be used as building blocks in countless combinations to produce nanomaterials with an incredible diversity ofmorphologies and functions. In this work, I investigate several examples of SAP NMs tocharacterize the assembly, architecture, and functional impact at near-atomic resolution. Specifically, I explore how intrinsically disordered peptides (IDPs) can be manipulated through external stimuli, including pH, metal ions, and post-translational modifications, to control the transition from disordered aggregates to ordered, fibrous networks. In my second chapter, I examine how peptide–π–peptide systems can adopt highly flexible conformations by introducing alkyl spacers. Furthermore, I investigate how the sequence-structure relationship affects polymorphic fibril formation of an anti-parallel β-hairpin forming peptide. In my final chapter, I use cryo-ET to examine the mechanisms governing cell death in metastatic osteoblastic castration-resistant prostate cancer (mCRPC) cells after treatment with a therapeutic, enzyme-activated, peptide pBP-NBD, and show how self-assembly of pPB-NBD triggers intracellular fibril formation, organelle disruption, and apoptotic cell death.
ProQuest ID
Recommended Citation
Rich-New, Shane Thomas, "Legos Of Life: Modularity And Mechanisms In Peptide Nanomaterial Design" (2025). All ETDs from UAB. 7365.
https://digitalcommons.library.uab.edu/etd-collection/7365
