Engineering Asymmetric Peptide Membranes Open Access

Li, Sha (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/p2676w277?locale=en
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Abstract

Peptide self-assembly offers rich opportunities for the controlled synthesis of supramolecular architectures with unique structural features and functions. Historically, this area has been inspired by the elaborate assemblies of biological systems. Despite this precedent, generating asymmetrical structures with optical and electrical functions has proven challenging. The nucleating core of the Alzheimer's disease peptide, Aβ(16-22) or KLVFFAE, has been heavily studied and characterized to the point where specific assembly codes are now emerging. In this dissertation, I expanded the molecular recognition codes from Aβ(16-22), a single-component system, to multi-component systems that enable us to build asymmetry into self-assembled networks. Strategies to engineer the peptide membrane surfaces were systematically investigated and novel biophysical methods including utilizing Electrostatic Force Microscopy and solid-state NMR to characterize complex co-assemblies were developed to define the unique asymmetric charged surfaces and segregated domains of the peptide membranes. Furthermore, I demonstrate the potential of these assemblies for donor-acceptor arrays transferring energy and electrons across the peptide membranes. Taken together, I argue that amyloid peptide membranes present robust and patterned surfaces capable of routinely controlling asymmetry and extending the capabilities of biological membranes. Developing these systems for light-harvesting and charge separation of artificial photosynthesis is now within reach.

Table of Contents

Chapter 1 Exploiting Biomimetic Strategies to Expand the Horizons of Self-assembly 1
From Supramolecular Chemistry to System Chemistry 1
Designing Asymmetry in Nonbiological Self-assembly Systems 2
Amyloid β Peptide Self-Assembles into Ordered Bilayer Architectures 3
Molecular Recognition Codes Direct Peptide Assembly 5
Nucleation and Seeded Growth in Amyloid Self-Assembly 7
Engineering Cross-β Peptide Surfaces for New Functions 9
Chapter 2 Construction of Patterned Phosphorylated Peptide Membranes 15
INTRODUCTION 15
RESULTS 16
Self-Assembly of Phosphorylated Peptide Membranes 16
Structural Characterization of Phosphorylated Peptide Assemblies 20
Diversifying Negatively-Charged Peptide Nanotube Surfaces 25
Solvent and Temperature Dependence of Phospohorylated Peptide Membranes 29
AuNPs Binding with Peptide Membranes 31
Salt-induced Macroscale Assembly of Peptide Nanotubes 33
Development of Electrostatic Force Microscopy 35
Analysis of Supramolecular Assemblies via Electrostatic Force Microscopy 37
Small Molecules Binding with Phosphorylated Peptide Nanotube Surfaces 40
Neurofibrillar Tangle Surrogates: Histone H1 Binding to Phosphotyrosine Peptide Nanotubes 41
CONCLUSIONS 48
METHODS 49
Chapter 3 Generating Asymmetric Peptide Membranes 60
INTRODUCTION 60
RESULTS 60
Model of Asymmetric Peptide Membranes 60
Preliminary Evaluation of Peptide Mixing 61
Structural Characterization of the Co-Assembly 63
Thermal Studies of the Co-Assembly 67
Surface Charge Evaluation via Salt Bundling 71
Surface Charge Evaluation via Electrostatic Force Microscopy 72
Peptide Registry Characterization via Solid-State REDOR NMR 74
Peptide Interfaces Analysis 79
Domain Segregation Built upon Cross-Seeding 81
Exploit Surface Charge Distribution and N-terminal Residue Sizes 97
Exploit Peptide Specificity in Co-Assembly 100
CONCLUSIONS 103
METHODS 105
Chapter 4 Energy and Electron Transfer across Asymmetric Peptide Membranes 117
INTRODUCTION 117
RESULTS 118
Covalent Coupling of Flurophores to Peptide Membrane Surfaces 118
Noncovalent Association of Flurophores to Peptide Membrane Surfaces 122
Energy Transfer across Asymmetric Cross-β Peptide Membranes 126
Electron Transfer across Asymmetric Cross- β Peptide Membranes 132
CONCLUSIONS 146
METHODS 146
Chapter 5 Assembly of Lipid-Peptide Chimeras 152
INTRODUCTION 152
RESULTS 156
Accommodating Unsaturated Lipid Chains within Aβ Peptide Membranes 156
Self-assembly and Structural Characterization of Lipid-Peptide Chimeras 160
Thermal Studies of Lipid-Peptide Chimeras 164
Modulating Conformation and Aggregation Capability of Peptides via Lipidation 168
Coassembly of Lipid-Peptide Chimeras 179
Cross-Seeding of Lipid-Peptide Chimeras 184
CONCLUSIONS 194
METHODS 195
Chapter 6 Engineering Asymmetric Cross-β Peptide Membranes for Emergent Functions 201
Surface Engineering of Peptide Membranes 201
Surface Characterization of Peptide Membranes 203
Design Asymmetry and Control Defects in Multicomponent Self-Assembly 203
Expand Molecular Codes for Supramolecular Self-Assembly 204
Toward Dynamic Functional Self-Assembly System 205

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