Investigating Biologically Derived Cationic Self-Assembling Peptides for Antimicrobial Applications and as Scaffolded Nanomaterials Restricted; Files Only
Laguera, Breana (Fall 2025)
Abstract
Cationic peptides are evolutionarily developed biomolecules that serve a range of structural and immunological functions in biological systems. Cationic antimicrobial peptides (AMPs), part of the innate immune system in virtually all organisms, contain amphipathic sequence patterns that drive both membrane-disruptive activity and self-assembly into supramolecular structures, though the relationship between these dual behaviors remains in question. To address this, the first two studies presented here systematically investigate cationic AMP variants with sequence and terminal modifications to probe the effect of sequence on structure and function, namely, membrane-disrupting effects. The first two studies reveal a reciprocal relationship between peptide self-assembly and antimicrobial activity, specifically that stabilizing higher-order structures decreases biological activity. Expanding on peptide charge interactions, the third presented study utilizes DNA nanotubes as scaffolds to predictably and consistently load a cationic collagen mimetic peptide (CMP), to develop a novel DNA-peptide hybrid nanostructure. Together, these projects contribute to a better understanding of the design rules necessary for cationic peptide optimization across medicinal and nanomaterial contexts.
Table of Contents
1) Chapter 1: Introduction
1.1 Motivation for this study
1.2 Cationic AMPs
1.2.1 AMP Mechanisms of action
1.3 Principles of peptide self-assembly
1.4 Self-assembling AMPs
1.4.1 Secondary structure of ffAMPs
1.4.2 Amphibian sourced ffAMPs
1.4.3 Biological activity of self-assembling amphibian AMPs
1.5 Engineered sequence modifications in ffAMPs to tune self-assembly and activity
1.6 DNA Nanotechnology utilized in AMP development
1.7 Aims and scope of this dissertation
1.8 References
2 Chapter 2: Amphipathic antimicrobial peptides illuminate the relationship between self-assembly and cytolytic activity
2.1 Introduction
2.2 Results and discussion
2.3 Conclusion
2.4 Materials and methods
2.4.1 Materials
2.4.2 Methods
2.5 Supplemental Figures
2.6 References
3 Chapter 3: Sequence-driven self-assembly and antimicrobial activity of temporin derivatives
3.1 Introduction
3.2 Results and Discussion
3.2.1 Structural characterization of TSHa K2 Mutants
3.2.2 Structural Characterization of TSHa K3 Mutants
3.2.3 Biological activity
3.3 Discussion
3.4 Conclusions
3.5 Materials and methods
3.5.1 Methods
3.6 References
4 Chapter 4: Electrostatically mediated loading of cationic peptides onto DNA nanotechnology to produce a hybrid nanostructure
4.1 Introduction
4.2 Results and Discussion
4.2.1 Collagen-mimetic peptide screening
4.2.2 DNA nanotube characterization
4.2.3 Peptide-DNT Screening
4.3 Conclusions and Future Directions
4.4 Materials and methods
4.4.1 Collagen mimetic peptides
4.4.2 Methods
4.5 References
5 Chapter 5: Conclusion and Future Outlook
5.1 Summary of Major Findings
5.2 Limitations and Open Questions
5.3 Future Outlook
5.4 References
About this Dissertation
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File download under embargo until 12 January 2028 | 2025-10-30 17:27:58 -0400 | File download under embargo until 12 January 2028 |
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