Biological and Bio-inspired Nanomaterials (eBook)

Contents 5
1 Dynamics and Control of Peptide Self-Assembly and Aggregation 7
1.1 Introduction 8
1.2 Kinetic Theory of Protein Aggregation 9
1.2.1 Fundamental Processes in Protein Aggregation 9
1.2.2 The Master Equation: Quantifying the Kinetics of Aggregation 11
1.2.3 Principal Moments and Moment Equations 14
1.2.3.1 Principal Moments 14
1.2.3.2 Moment Equations 15
1.2.3.3 Common Approximations 15
1.2.4 Solving the Moment Equations: The Fixed-Point Method 17
1.2.5 Implications from Integrated Rate Laws 18
1.2.5.1 Early-Time Behaviour is Exponential 19
1.2.5.2 Half-Times and Scaling Exponents 20
1.3 The Full Aggregation Network: Interplay and Competition 21
1.3.1 Monomer Dependence of the Scaling Exponent as a Guide to Complex Mechanisms 21
1.3.2 Saturation: Processes in Series 23
1.3.2.1 Multi-step Elongation 24
1.3.2.2 Multi-step Primary Nucleation 26
1.3.2.3 Multi-step Secondary Nucleation 26
1.3.3 Competition: Processes in Parallel 27
1.3.3.1 Competition Between Primary and Secondary Processes 28
1.3.3.2 Two Competing Secondary Processes 28
1.3.4 Representing the Reaction Network 29
1.4 Application to Experiment: Global Fitting of Kinetic Data 31
1.5 Controlling Aggregation: Inhibitors and Solution Conditions 32
1.6 Conclusions 35
References 36
2 Peptide Self-Assembly and Its Modulation: Imaging on the Nanoscale 40
Abbreviations 40
2.1 Introduction 41
2.2 Peptide Self-Assembly Structures on Surfaces 42
2.3 Mutation/Modification Effects on Peptide Assemblies 45
2.4 Coassembly of Peptides with Small Molecules 49
2.4.1 Small Molecules Interacting with the Termini of Peptides 49
2.4.2 Small Molecules Interacting with the Side Groups of Peptides 52
2.5 Correlation of Peptide Assemblies on Surfaces and in Solution 56
2.6 Conclusions and Perspectives 59
References 59
3 The Kinetics, Thermodynamics and Mechanisms of Short Aromatic Peptide Self-Assembly 66
3.1 Introduction 67
3.2 The Nature of the Interactions Responsible for Peptide Assembly 68
3.2.1 Hydrogen Bonding 68
3.2.2 Hydrophobicity 70
3.2.3 Aromaticity in Proteins and Short Peptides 71
3.3 The Role of Phenylalanine Residues in Peptide Self-Assembly into Amyloid Fibrils 73
3.4 Experimental Methods to Study Short Peptide Assembly 74
3.4.1 The Choice of the Assembly Conditions for Self-Assembly 74
3.4.2 Microscopic Methods 76
3.4.3 Spectroscopic Methods 76
3.4.4 Scattering, Rheological, Calorimetric and Conductivity-Based Methods 77
3.4.5 Microfluidics 78
3.5 Thermodynamic Stability of Peptide Assemblies 79
3.5.1 Thermal Stability of FF Crystals 79
3.5.2 Chemical Stability of FF Crystals 80
3.5.3 Non-crystalline Short Aromatic Peptide Assemblies 81
3.5.3.1 Fibrils and Gels 81
3.5.3.2 Amorphous Materials 84
3.6 Mechanistic and Kinetic Description of Aromatic Peptide Assembly 87
3.6.1 Growth Processes 87
3.6.2 Nucleation Processes 90
3.7 Structure of Dipeptide Crystals with Particular Emphasis on FF 92
3.7.1 Hydrophobic Structures in Aromatic Dipeptides 93
3.7.2 Hydrogen Bond Connectivity in Aromatic Dipeptides 93
3.7.3 Macroscale Aggregate Structure 96
3.8 Comparison with the Assembly of Longer Sequences into Amyloid Fibrils 97
3.8.1 Structural Comparison 97
3.8.2 Comparison of Assembly Kinetics and Thermodynamics of Short Aromatic Peptides and Longer Amyloid Forming Sequences 101
3.9 Conclusions and Future Perspectives 106
References 107
4 Bacterial Amyloids: Biogenesis and Biomaterials 118
4.1 Introduction 119
4.2 The Curli System: Quality-Conscious and Made to Last 119
4.2.1 The Partnership of CsgB and CsgA: An Anchor for a Roving Sailor 121
4.2.2 All in the Fibril Family: Cooperation Within the Curli Operon 122
4.2.3 Younger Kid on the Block: Fap Fimbria Are Composed of Mainly FapC 124
4.2.4 Another Study in Team-Work: The Role of Fap Proteins 125
4.2.5 Other Bacterial Amyloid Systems 127
4.2.5.1 TasA: Cell Anchoring and Susceptibility to D-Amino Acids 127
4.2.5.2 MspA: The First Archaeal FuBA 132
4.2.5.3 Harpins: Green Oligomeric Weapons 132
4.2.5.4 Chaplins: Breaking the Air-Water Interface Barrier 132
4.2.5.5 Phenol-Soluble Modulins (PSM): Amyloid or Antimicrobial Agents? 133
4.3 Functional Amyloids in silico 133
4.3.1 Predicting Aggregation and Amyloid Propensity of Proteins Based on Sequences 133
4.3.1.1 Secondary Structure Propensity and Physico-Chemical Properties of Amino Acids 137
4.3.1.2 Statistical Potentials 137
4.3.1.3 Statistical Mechanical Models 138
4.3.1.4 Experimentally Driven Methods 139
4.3.1.5 Machine Learning Methods 139
4.3.1.6 Consensus Predictors 140
4.3.2 Detecting Amyloid Prone Sequences in Functional Amyloids 140
4.3.2.1 Sequence-Based Methods Can Detect Amyloidogenic Segments in Biofilm-Associated Proteins 140
4.3.2.2 Searching for Prion-like Domains Can Uncover Previously Unknown Functional Amyloids 140
4.3.2.3 The Existence of Imperfect Repeats Is Common to Many Functional Amyloids 141
4.3.3 Identifying Functional Amyloids Based on Their Evolved Characteristics 141
4.3.3.1 Searching for Functional Amyloid Homologues in Large Sequence Databases Reveals Functional Amyloid Sequence Diversity, Phylogeny, and Operon Structure 142
4.3.3.2 Techniques Targeting Evolved Characteristics May Find Unknown Functional Amyloids 143
4.3.4 Structure Prediction and Simulations of Functional Amyloids 144
4.3.4.1 Molecular Modeling Techniques Can Propose Structural Models of Functional Amyloids without Experimental Structural Data Using Evolutionary Constraints 144
4.3.4.2 Simulation Can Help to Elucidate the Molecular Details of Functional Amyloid Formation 145
4.4 Uses for Functional Amyloid: Brave New Nanomaterials 146
4.4.1 C-DAG as a Screen for Amyloid: How to Hijack a Robust Amyloid Export System 146
4.4.1.1 Generating New Binding Properties: How to Hitch a Ride on the Amyloid Ladder 147
4.4.1.2 Amyloid as Underwater Glue: Fusing CsgA to Mussel Foot Proteins 148
4.4.1.3 Controlled Combination of Different Amyloid: The Power of Riboregulators 148
4.4.2 Controlling Amyloid with Co-Factors: The Case of the Missing Calcium 150
4.4.3 Inclusion Bodies with Tunable Porosity: Nanopills for Drug Delivery? 151
4.4.4 Other Amyloid Uses: From Macroscale Films to Bone Replacement and Tissue Engineering 151
4.5 Perspectives 152
4.5.1 Challenges in the Development of New Amyloid-Based Biomaterials and -Medicine 153
References 154
5 Fungal Hydrophobins and Their Self-Assembly into Functional Nanomaterials 165
5.1 Introduction 166
5.2 The Discovery of Hydrophobins 166
5.3 Class I and Class II Hydrophobins 168
5.4 Structures of Class I and Class II Hydrophobins 170
5.5 The Surface Activity of Hydrophobins 171
5.6 Mechanism of Hydrophobin Assembly from Monomer to Amphipathic Monolayer 172
5.7 Hydrophobins Have Multiple Functions in the Fungal Life Cycle 175
5.7.1 Hydrophobin Coatings Shield Fungal Structures from Host Immune Recognition 175
5.7.2 Hydrophobins Facilitate Attachment of Fungi to Host Cells for Colonisation 177
5.8 Harnessing Hydrophobins for Biotechnological Purposes 177
5.8.1 Hydrophobins Used to Modify or to Functionalise Surfaces 178
5.8.2 Hydrophobins Used to Coat Stents for Anti-Fouling Properties 181
5.8.3 Hydrophobins Used to Stabilise Emulsions 181
5.8.4 Hydrophobins Applied for Improved Drug Delivery 182
5.9 Conclusions 183
References 184
6 Nanostructured, Self-Assembled Spider Silk Materials for Biomedical Applications 190
6.1 Introduction 190
6.2 Natural Spider Silk 191
6.2.1 Protein Composition of Major Ampullate Silk 192
6.2.2 Processing of Spider Silk Proteins into Fibers 193
6.2.3 Structure-Mechanics Relationships 194
6.3 Recombinant Spider Silk Proteins 197
6.3.1 Self-Assembly of Artificial Spider Silk Proteins 197
6.3.2 Materials Made of Recombinant Spider Silk Proteins 199
6.3.2.1 Nanofibrils 199
6.3.2.2 Hydrogels 203
6.3.2.3 Particles 203
6.3.2.4 Capsules 203
6.3.2.5 Films 204
6.3.2.6 Foams and Sponges 204
6.4 Biomedical Applications of Spider Silk 205
6.4.1 Drug Delivery and Deposition 206
6.4.2 Tissue Engineering 207
6.4.2.1 Wound Healing Scaffolds 208
6.4.2.2 Bone Tissue Engineering 209
6.4.2.3 Nerve Tissue Engineering 210
6.4.2.4 Implant Coating 211
6.5 Biofabrication 212
6.6 Conclusions 214
References 214
7 Protein Microgels from Amyloid Fibril Networks 225
7.1 Nature of Amyloid Proteins 226
7.1.1 Introduction 226
7.1.2 Detection of Amyloid Structures 229
7.1.3 Structure of Amyloid Fibrils 229
7.1.4 Self-Assembly and Polymorphism of Amyloid Fibrils 231
7.1.5 Mechanical Properties of Amyloid Fibrils 232
7.2 Amyloid Proteins for the Development of Functional Microgels 234
7.2.1 Emerging Applications of Artificial Amyloid Protein-Based Materials and Microgels 234
7.2.1.1 Amyloid Microgels as Drug Carrier Agents 235
7.2.2 Microgel and Microcapsule Formation 236
7.2.2.1 Microgel Formation Techniques 236
7.2.2.2 Structural Changes Accompanying the Formation of Protein Microgels and Protein Microgel Stability 239
7.2.3 Case Study: The Development of Protein Microgels and Gel Shells from Amyloid Fibril Networks as Drug Carrier Agents 241
7.2.4 Multiphase Protein Microgels – Phase Separation Phenomenon in Microgels 245
7.2.5 Microgels from All-Aqueous Emulsions Stabilized by Amyloid Nanofibrils 247
7.2.6 Functionalized Proteinaceous Microgels 250
7.3 Conclusions 253
References 253
8 Protein Nanofibrils as Storage Forms of Peptide Drugs and Hormones 266
8.1 Introduction 266
8.2 Functional Amyloids 269
8.3 Amyloids as a Depot for Protein/Peptide Storage and Release 269
8.4 Amyloid as Long-Acting Depot Formulations 277
8.5 Conclusion 284
References 285
9 Nanozymes: Biomedical Applications of Enzymatic Fe3O4 Nanoparticles from In Vitro to In Vivo 292
Abbreviations 292
9.1 Introduction 293
9.2 Basic Features of Fe3O4 Nanozymes 294
9.2.1 Activities of Fe3O4 Nanozymes 294
9.2.2 Kinetics and Mechanism of Fe3O4 Nanozymes 295
9.2.3 Advantages of Fe3O4 Nanozymes 296
9.3 Biomedical Applications of Fe3O4 Nanozymes 298
9.3.1 In Vitro Bioassays 298
9.3.2 Ex Vivo Tracking and Histochemistry Diagnosis 300
9.3.3 In Vivo Oxidative Stress Regulation 302
9.3.4 Hygiene and Dental Therapy 305
9.3.5 Eco Environment Applications 306
9.4 Summary and Future Perspectives 307
References 308
10 Self-Assembly of Ferritin: Structure, Biological Function and Potential Applications in Nanotechnology 314
10.1 Introduction 315
10.2 Historical Perspective 315
10.3 Ferritin: Basic Biology 317
10.4 Ferritin Protein Family 318
10.5 Structure of Ferritin 320
10.6 Application of Ferritin in Nanotechnology 322
10.7 Drug Delivery and Ferritin 323
10.8 Surface Modification and Cellular Interactions of Ferritin Nanoparticles 324
10.9 Other Potential Applications of Ferritin 325
10.10 Conclusions and Future Perspectives of Ferritin in Nano-biology 326
References 327
11 DNA Nanotechnology for Building Sensors, Nanopores and Ion-Channels 331
11.1 Self-Assembly with DNA 332
11.1.1 DNA Lattices and Tiles 332
11.1.2 DNA Origami 334
11.1.3 Design and Assembly of DNA Nanostructures 336
11.1.3.1 Conceiving the Target Shape 336
11.1.3.2 Crossover Rules for DNA Nanostructures 337
11.1.3.3 Computational Tools for DNA Nanotechnology 338
11.1.3.4 Assembly and Stability of DNA Nanostructures 340
11.1.4 Experimental Characterisation of DNA Nanostructures 341
11.1.4.1 UV-Vis Spectroscopy 341
11.1.4.2 UV Melting Profile 341
11.1.4.3 Gel Electrophoresis 342
11.1.4.4 Dynamic Light Scattering 343
11.1.4.5 AFM and TEM 344
11.1.4.6 DNA-PAINT 345
11.1.4.7 Functionalisation of DNA 345
11.2 DNA Sensors and Nanopores 346
11.2.1 Nanomechanical DNA-Based Sensors 347
11.2.1.1 Molecular Sensors 347
11.2.1.2 Environmental Sensors 348
11.2.2 Nanopores for Single-Molecule Detection 348
11.2.3 DNA Nanotechnology for Enhanced Nanopore Sensing 350
11.2.4 DNA Origami Hybrid Nanopores 352
11.2.4.1 Nanopore Architecture By Design 353
11.2.4.2 Tunable Pore Diameter 353
11.2.4.3 High Specificity 353
11.2.4.4 Stimuli Response 354
11.2.4.5 Ease of Fabrication 354
11.3 Synthetic Membrane Nanopores 355
11.3.1 Membrane Pores in Nature 356
11.3.2 Milestones of Synthetic Membrane Pores 357
11.3.3 DNA-Based Membrane Pores 359
References 362
12 Bio Mimicking of Extracellular Matrix 371
Abbreviations 371
12.1 Introduction 372
12.2 The Extracellular Matrix 373
12.3 Classification of Biomaterials 374
12.4 Synthetic Biomaterials 375
12.4.1 Metallic Biomaterials 375
12.4.2 Ceramic Biomaterials 377
12.4.3 Synthetic Biodegradable Polymers 379
12.5 Natural Biomaterials 380
12.5.1 Collagen 380
12.5.2 Alginate 382
12.5.3 Cellulose 384
12.5.4 Chitin-Chitosan 384
12.6 Natural and Synthetic Composite Biomaterials 385
12.7 Supramolecular Soft Biomaterials (Hydrogels) 386
12.8 How to Design the Molecular Building Blocks for Hydrogels 386
12.8.1 Mimicking the Microarchitecture of the Native ECM with Engineered Scaffolds 386
12.8.2 Microarchitecture of Tissue-Engineered Scaffolds 387
12.9 Hydrogel Degradation 389
12.10 Bioadhesion and Bioactivity 389
12.11 3D Structures of Hydrogels 390
12.12 Conclusions 391
References 392
13 Bioinspired Engineering of Organ-on-Chip Devices 400
Abbreviations 401
13.1 Introduction 401
13.2 Microfluidic Cell Culture System 402
13.3 Microengineering the Cellular Microenvironment 404
13.3.1 Cell-Matrix Interaction 405
13.3.2 Cell-Cell Interactions 405
13.3.3 Control of Biochemical Microenvironments 406
13.3.3.1 Gradients of Soluble Factors 406
13.3.3.2 Control of Oxygen Concentration 407
13.3.4 Control of Biophysical Microenvironments 408
13.3.4.1 Fluid Flow-Induced Stress 408
13.3.4.2 Tissue Mechanics 409
13.4 From Cells-on-Chip to Organs-on-Chips 409
13.4.1 Bioengineering Organs on Chip 414
13.4.1.1 Lung on a Chip 414
13.4.1.2 Gastrointestines on a Chip 415
13.4.1.3 Liver on a Chip 417
13.4.1.4 Heart on a Chip 418
13.4.1.5 Blood-Brain-Barrier on Chip 419
13.4.1.6 Multiple Organs on a Chip 419
13.4.2 Integrated Analysis System 421
13.5 Proof-of-Concept Applications of Organs-on-Chip 422
13.5.1 Disease Modeling 422
13.5.1.1 Inflammatory-Related Diseases 422
13.5.1.2 Brain diseases on Chip 423
13.5.1.3 Cancers on Chip 424
13.5.2 Drug Testing 425
13.5.2.1 Efficacy and Toxicity Testing 425
13.5.2.2 Pharmacokinetic and Pharmacodynamic Studies 427
13.5.3 Host-Microbe Interaction 429
13.6 Conclusion and Outlooks 430
References 431