Biological and Bio-inspired Nanomaterials - Properties and Assembly Mechanisms

Contents

1 Dynamics and Control of Peptide Self-Assembly and Aggregation

1.1 Introduction

1.2 Kinetic Theory of Protein Aggregation

1.2.1 Fundamental Processes in Protein Aggregation

1.2.2 The Master Equation: Quantifying the Kinetics of Aggregation

1.2.3 Principal Moments and Moment Equations

1.2.3.1 Principal Moments

1.2.3.2 Moment Equations

1.2.3.3 Common Approximations

1.2.4 Solving the Moment Equations: The Fixed-Point Method

1.2.5 Implications from Integrated Rate Laws

1.2.5.1 Early-Time Behaviour is Exponential

1.2.5.2 Half-Times and Scaling Exponents

1.3 The Full Aggregation Network: Interplay and Competition

1.3.1 Monomer Dependence of the Scaling Exponent as a Guide to Complex Mechanisms

1.3.2 Saturation: Processes in Series

1.3.2.1 Multi-step Elongation

1.3.2.2 Multi-step Primary Nucleation

1.3.2.3 Multi-step Secondary Nucleation

1.3.3 Competition: Processes in Parallel

1.3.3.1 Competition Between Primary and Secondary Processes

1.3.3.2 Two Competing Secondary Processes

1.3.4 Representing the Reaction Network

1.4 Application to Experiment: Global Fitting of Kinetic Data

1.5 Controlling Aggregation: Inhibitors and Solution Conditions

1.6 Conclusions

References

2 Peptide Self-Assembly and Its Modulation: Imaging on the Nanoscale

Abbreviations

2.1 Introduction

2.2 Peptide Self-Assembly Structures on Surfaces

2.3 Mutation/Modification Effects on Peptide Assemblies

2.4 Coassembly of Peptides with Small Molecules

2.4.1 Small Molecules Interacting with the Termini of Peptides

2.4.2 Small Molecules Interacting with the Side Groups of Peptides

2.5 Correlation of Peptide Assemblies on Surfaces and in Solution

2.6 Conclusions and Perspectives

References

3 The Kinetics, Thermodynamics and Mechanisms of Short Aromatic Peptide Self-Assembly

3.1 Introduction

3.2 The Nature of the Interactions Responsible for Peptide Assembly

3.2.1 Hydrogen Bonding

3.2.2 Hydrophobicity

3.2.3 Aromaticity in Proteins and Short Peptides

3.3 The Role of Phenylalanine Residues in Peptide Self-Assembly into Amyloid Fibrils

3.4 Experimental Methods to Study Short Peptide Assembly

3.4.1 The Choice of the Assembly Conditions for Self-Assembly

3.4.2 Microscopic Methods

3.4.3 Spectroscopic Methods

3.4.4 Scattering, Rheological, Calorimetric and Conductivity-Based Methods

3.4.5 Microfluidics

3.5 Thermodynamic Stability of Peptide Assemblies

3.5.1 Thermal Stability of FF Crystals

3.5.2 Chemical Stability of FF Crystals

3.5.3 Non-crystalline Short Aromatic Peptide Assemblies

3.5.3.1 Fibrils and Gels

3.5.3.2 Amorphous Materials

3.6 Mechanistic and Kinetic Description of Aromatic Peptide Assembly

3.6.1 Growth Processes

3.6.2 Nucleation Processes

3.7 Structure of Dipeptide Crystals with Particular Emphasis on FF

3.7.1 Hydrophobic Structures in Aromatic Dipeptides

3.7.2 Hydrogen Bond Connectivity in Aromatic Dipeptides

3.7.3 Macroscale Aggregate Structure

3.8 Comparison with the Assembly of Longer Sequences into Amyloid Fibrils

3.8.1 Structural Comparison

3.8.2 Comparison of Assembly Kinetics and Thermodynamics of Short Aromatic Peptides and Longer Amyloid Forming Sequences

3.9 Conclusions and Future Perspectives

References

4 Bacterial Amyloids: Biogenesis and Biomaterials

4.1 Introduction

4.2 The Curli System: Quality-Conscious and Made to Last

4.2.1 The Partnership of CsgB and CsgA: An Anchor for a Roving Sailor

4.2.2 All in the Fibril Family: Cooperation Within the Curli Operon

4.2.3 Younger Kid on the Block: Fap Fimbria Are Composed of Mainly FapC

4.2.4 Another Study in Team-Work: The Role of Fap Proteins

4.2.5 Other Bacterial Amyloid Systems

4.2.5.1 TasA: Cell Anchoring and Susceptibility to D-Amino Acids

4.2.5.2 MspA: The First Archaeal FuBA

4.2.5.3 Harpins: Green Oligomeric Weapons

4.2.5.4 Chaplins: Breaking the Air-Water Interface Barrier

4.2.5.5 Phenol-Soluble Modulins (PSM): Amyloid or Antimicrobial Agents?

4.3 Functional Amyloids in silico

4.3.1 Predicting Aggregation and Amyloid Propensity of Proteins Based on Sequences

4.3.1.1 Secondary Structure Propensity and Physico-Chemical Properties of Amino Acids

4.3.1.2 Statistical Potentials

4.3.1.3 Statistical Mechanical Models

4.3.1.4 Experimentally Driven Methods

4.3.1.5 Machine Learning Methods

4.3.1.6 Consensus Predictors

4.3.2 Detecting Amyloid Prone Sequences in Functional Amyloids

4.3.2.1 Sequence-Based Methods Can Detect Amyloidogenic Segments in Biofilm-Associated Proteins

4.3.2.2 Searching for Prion-like Domains Can Uncover Previously Unknown Functional Amyloids

4.3.2.3 The Existence of Imperfect Repeats Is Common to Many Functional Amyloids

4.3.3 Identifying Functional Amyloids Based on Their Evolved Characteristics

4.3.3.1 Searching for Functional Amyloid Homologues in Large Sequence Databases Reveals Functional Amyloid Sequence Diversity, Phylogeny, and Operon Structure

4.3.3.2 Techniques Targeting Evolved Characteristics May Find Unknown Functional Amyloids

4.3.4 Structure Prediction and Simulations of Functional Amyloids

4.3.4.1 Molecular Modeling Techniques Can Propose Structural Models of Functional Amyloids without Experimental Structural Data Using Evolutionary Constraints

4.3.4.2 Simulation Can Help to Elucidate the Molecular Details of Functional Amyloid Formation

4.4 Uses for Functional Amyloid: Brave New Nanomaterials

4.4.1 C-DAG as a Screen for Amyloid: How to Hijack a Robust Amyloid Export System

4.4.1.1 Generating New Binding Properties: How to Hitch a Ride on the Amyloid Ladder

4.4.1.2 Amyloid as Underwater Glue: Fusing CsgA to Mussel Foot Proteins

4.4.1.3 Controlled Combination of Different Amyloid: The Power of Riboregulators

4.4.2 Controlling Amyloid with Co-Factors: The Case of the Missing Calcium

4.4.3 Inclusion Bodies with Tunable Porosity: Nanopills for Drug Delivery?

4.4.4 Other Amyloid Uses: From Macroscale Films to Bone Replacement and Tissue Engineering

4.5 Perspectives

4.5.1 Challenges in the Development of New Amyloid-Based Biomaterials and -Medicine

References

5 Fungal Hydrophobins and Their Self-Assembly into Functional Nanomaterials

5.1 Introduction

5.2 The Discovery of Hydrophobins

5.3 Class I and Class II Hydrophobins

5.4 Structures of Class I and Class II Hydrophobins

5.5 The Surface Activity of Hydrophobins

5.6 Mechanism of Hydrophobin Assembly from Monomer to Amphipathic Monolayer

5.7 Hydrophobins Have Multiple Functions in the Fungal Life Cycle

5.7.1 Hydrophobin Coatings Shield Fungal Structures from Host Immune Recognition

5.7.2 Hydrophobins Facilitate Attachment of Fungi to Host Cells for Colonisation

5.8 Harnessing Hydrophobins for Biotechnological Purposes

5.8.1 Hydrophobins Used to Modify or to Functionalise Surfaces

5.8.2 Hydrophobins Used to Coat Stents for Anti-Fouling Properties

5.8.3 Hydrophobins Used to Stabilise Emulsions

5.8.4 Hydrophobins Applied for Improved Drug Delivery

5.9 Conclusions

References

6 Nanostructured, Self-Assembled Spider Silk Materials for Biomedical Applications

6.1 Introduction

6.2 Natural Spider Silk

6.2.1 Protein Composition of Major Ampullate Silk

6.2.2 Processing of Spider Silk Proteins into Fibers

6.2.3 Structure-Mechanics Relationships

6.3 Recombinant Spider Silk Proteins

6.3.1 Self-Assembly of Artificial Spider Silk Proteins

6.3.2 Materials Made of Recombinant Spider Silk Proteins

6.3.2.1 Nanofibrils

6.3.2.2 Hydrogels

6.3.2.3 Particles

6.3.2.4 Capsules

6.3.2.5 Films

6.3.2.6 Foams and Sponges

6.4 Biomedical Applications of Spider Silk

6.4.1 Drug Delivery and Deposition

6.4.2 Tissue Engineering

6.4.2.1 Wound Healing Scaffolds

6.4.2.2 Bone Tissue Engineering

6.4.2.3 Nerve Tissue Engineering

6.4.2.4 Implant Coating

6.5 Biofabrication

6.6 Conclusions

References

7 Protein Microgels from Amyloid Fibril Networks

7.1 Nature of Amyloid Proteins

7.1.1 Introduction

7.1.2 Detection of Amyloid Structures

7.1.3 Structure of Amyloid Fibrils

7.1.4 Self-Assembly and Polymorphism of Amyloid Fibrils

7.1.5 Mechanical Properties of Amyloid Fibrils

7.2 Amyloid Proteins for the Development of Functional Microgels

7.2.1 Emerging Applications of Artificial Amyloid Protein-Based Materials and Microgels

7.2.1.1 Amyloid Microgels as Drug Carrier Agents

7.2.2 Microgel and Microcapsule Formation

7.2.2.1 Microgel Formation Techniques

7.2.2.2 Structural Changes Accompanying the Formation of Protein Microgels and Protein Microgel Stability

7.2.3 Case Study: The Development of Protein Microgels and Gel Shells from Amyloid Fibril Networks as Drug Carrier Agents

7.2.4 Multiphase Protein Microgels – Phase Separation Phenomenon in Microgels

7.2.5 Microgels from All-Aqueous Emulsions Stabilized by Amyloid Nanofibrils

7.2.6 Functionalized Proteinaceous Microgels

7.3 Conclusions

References

8 Protein Nanofibrils as Storage Forms of Peptide Drugs and Hormones

8.1 Introduction

8.2 Functional Amyloids

8.3 Amyloids as a Depot for Protein/Peptide Storage and Release

8.4 Amyloid as Long-Acting Depot Formulations

8.5 Conclusion

References

9 Nanozymes: Biomedical Applications of Enzymatic Fe3O4 Nanoparticles from In Vitro to In Vivo

Abbreviations

9.1 Introduction

9.2 Basic Features of Fe3O4 Nanozymes

9.2.1 Activities of Fe3O4 Nanozymes

9.2.2 Kinetics and Mechanism of Fe3O4 Nanozymes

9.2.3 Advantages of Fe3O4 Nanozymes

9.3 Biomedical Applications of Fe3O4 Nanozymes

9.3.1 In Vitro Bioassays

9.3.2 Ex Vivo Tracking and Histochemistry Diagnosis

9.3.3 In Vivo Oxidative Stress Regulation

9.3.4 Hygiene and Dental Therapy

9.3.5 Eco Environment Applications

9.4 Summary and Future Perspectives

References

10 Self-Assembly of Ferritin: Structure, Biological Function and Potential Applications in Nanotechnology

10.1 Introduction

10.2 Historical Perspective

10.3 Ferritin: Basic Biology

10.4 Ferritin Protein Family

10.5 Structure of Ferritin

10.6 Application of Ferritin in Nanotechnology

10.7 Drug Delivery and Ferritin

10.8 Surface Modification and Cellular Interactions of Ferritin Nanoparticles

10.9 Other Potential Applications of Ferritin

10.10 Conclusions and Future Perspectives of Ferritin in Nano-biology

References

11 DNA Nanotechnology for Building Sensors, Nanopores and Ion-Channels

11.1 Self-Assembly with DNA

11.1.1 DNA Lattices and Tiles

11.1.2 DNA Origami

11.1.3 Design and Assembly of DNA Nanostructures

11.1.3.1 Conceiving the Target Shape

11.1.3.2 Crossover Rules for DNA Nanostructures

11.1.3.3 Computational Tools for DNA Nanotechnology

11.1.3.4 Assembly and Stability of DNA Nanostructures

11.1.4 Experimental Characterisation of DNA Nanostructures

11.1.4.1 UV-Vis Spectroscopy

11.1.4.2 UV Melting Profile

11.1.4.3 Gel Electrophoresis

11.1.4.4 Dynamic Light Scattering

11.1.4.5 AFM and TEM

11.1.4.6 DNA-PAINT

11.1.4.7 Functionalisation of DNA

11.2 DNA Sensors and Nanopores

11.2.1 Nanomechanical DNA-Based Sensors

11.2.1.1 Molecular Sensors

11.2.1.2 Environmental Sensors

11.2.2 Nanopores for Single-Molecule Detection

11.2.3 DNA Nanotechnology for Enhanced Nanopore Sensing

11.2.4 DNA Origami Hybrid Nanopores

11.2.4.1 Nanopore Architecture By Design

11.2.4.2 Tunable Pore Diameter

11.2.4.3 High Specificity

11.2.4.4 Stimuli Response

11.2.4.5 Ease of Fabrication

11.3 Synthetic Membrane Nanopores

11.3.1 Membrane Pores in Nature

11.3.2 Milestones of Synthetic Membrane Pores

11.3.3 DNA-Based Membrane Pores

References

12 Bio Mimicking of Extracellular Matrix

Abbreviations

12.1 Introduction

12.2 The Extracellular Matrix

12.3 Classification of Biomaterials

12.4 Synthetic Biomaterials

12.4.1 Metallic Biomaterials

12.4.2 Ceramic Biomaterials

12.4.3 Synthetic Biodegradable Polymers

12.5 Natural Biomaterials

12.5.1 Collagen

12.5.2 Alginate

12.5.3 Cellulose

12.5.4 Chitin-Chitosan

12.6 Natural and Synthetic Composite Biomaterials

12.7 Supramolecular Soft Biomaterials (Hydrogels)

12.8 How to Design the Molecular Building Blocks for Hydrogels

12.8.1 Mimicking the Microarchitecture of the Native ECM with Engineered Scaffolds

12.8.2 Microarchitecture of Tissue-Engineered Scaffolds

12.9 Hydrogel Degradation

12.10 Bioadhesion and Bioactivity

12.11 3D Structures of Hydrogels

12.12 Conclusions

References

13 Bioinspired Engineering of Organ-on-Chip Devices

Abbreviations

13.1 Introduction

13.2 Microfluidic Cell Culture System

13.3 Microengineering the Cellular Microenvironment

13.3.1 Cell-Matrix Interaction

13.3.2 Cell-Cell Interactions

13.3.3 Control of Biochemical Microenvironments

13.3.3.1 Gradients of Soluble Factors

13.3.3.2 Control of Oxygen Concentration

13.3.4 Control of Biophysical Microenvironments

13.3.4.1 Fluid Flow-Induced Stress

13.3.4.2 Tissue Mechanics

13.4 From Cells-on-Chip to Organs-on-Chips

13.4.1 Bioengineering Organs on Chip

13.4.1.1 Lung on a Chip

13.4.1.2 Gastrointestines on a Chip

13.4.1.3 Liver on a Chip

13.4.1.4 Heart on a Chip

13.4.1.5 Blood-Brain-Barrier on Chip

13.4.1.6 Multiple Organs on a Chip

13.4.2 Integrated Analysis System

13.5 Proof-of-Concept Applications of Organs-on-Chip

13.5.1 Disease Modeling

13.5.1.1 Inflammatory-Related Diseases

13.5.1.2 Brain diseases on Chip

13.5.1.3 Cancers on Chip

13.5.2 Drug Testing

13.5.2.1 Efficacy and Toxicity Testing

13.5.2.2 Pharmacokinetic and Pharmacodynamic Studies

13.5.3 Host-Microbe Interaction

13.6 Conclusion and Outlooks

References