Bio-nanoimaging
Protein Misfolding and Aggregation
- 1st Edition - November 5, 2013
- Imprint: Academic Press
- Editors: Vladimir N Uversky, Yuri Lyubchenko
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 3 9 4 4 3 1 - 3
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 9 7 8 2 1 - 9
Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and character… Read more
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Request a sales quoteBio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering:
- Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits
- Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers
- Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme aggregation, misfolded intermediate of a PDZ domain, and micelle formation by human islet amyloid polypeptide
Protein misfolding and aggregation is a fast-growing frontier in molecular medicine and protein chemistry. Related disorders include cataracts, arthritis, cystic fibrosis, late-onset diabetes mellitus, and numerous neurodegenerative diseases like Alzheimer's and Parkinson's. Nanoimaging technology has proved crucial in understanding protein-misfolding pathologies and in potential drug design aimed at the inhibition or reversal of protein aggregation. Using these technologies, researchers can monitor the aggregation process, visualize protein aggregates and analyze their properties.
- Provides practical examples of nanoimaging research from leading molecular biology, cell biology, protein chemistry, biotechnology, genetics, and pharmaceutical labs
- Includes over 200 color images to illustrate the power of various nanoimaging technologies
- Focuses on nanoimaging techniques applied to protein misfolding and aggregation in molecular medicine
Researchers and post-graduate students studying molecular medicine and molecular basis of disease, biotechnology, nanomedicine, pharmacology and drug discovery, molecular and cellular biology, biochemistry, biophysics, structural biology
- Chapter 1. Molecular Mechanisms of Protein Misfolding
- Abstract
- Introduction
- The Mechanism of Aggregation
- Structures of Protein Aggregates
- Protein Aggregation Pathways
- Conclusions
- References
- Part I: Nanoimaging and Nanotechnology of Aggregating Proteins: A. In Vitro Approaches
- Chapter 2. Amyloid Fibril Length Quantification by Atomic Force Microscopy
- Abstract
- Acknowledgments
- Background
- Acquiring Images for Length Quantification
- Single-Particle Measurements of Individual Fibril Length
- Distributions of Fibril Length
- Prospects for Fibril Length Distribution Analysis
- References
- Chapter 3. Imaging Nucleation, Growth and Heterogeneity in Self-Assembled Amyloid Phases
- Abstract
- Acknowledgments
- Introduction
- Diversity in cross-β Assemblies
- Particle Phases
- Paracrystallization
- Paracrystalline Polymorphism
- Functional Energy Transfer
- Closing Perspective
- References
- Chapter 4. Molecular-Level Insights into Amyloid Polymorphism from Solid-State Nuclear Magnetic Resonance
- Abstract
- Acknowledgments
- Introduction
- Self-Propagating Molecular-Level Polymorphism in Aβ1-40 Fibrils
- Competition Between Parallel and Antiparallel β-Sheets in D23N-Aβ1-40 Fibrils
- pH-Dependent Cross-β Motif in Aβ11-25 Fibrils
- Polymorphism in Prion Fibrils
- Future Directions
- References
- Chapter 5. Single-Molecule Imaging of Amyloid-β Protein (Aβ) of Alzheimer’s Disease: From Single-Molecule Structures to Aggregation Mechanisms and Membrane Interactions
- Abstract
- Introduction
- Principles of High-Resolution Imaging by STM and AFM
- Monomeric and Oligomeric Structures of Aβ Determined by STM and AFM
- Mechanism of Aβ Fibrillogenesis Examined by AFM
- Aβ Structure on Model Membranes Examined by High-Resolution AFM
- Models of Aβ Structure Based on High-Resolution Imaging
- References
- Chapter 6. Nanomechanics of Neurotoxic Proteins: Insights at the Start of the Neurodegeneration Cascade
- Abstract
- Acknowledgments
- Introduction
- Intrinsically Disordered Proteins: Central Roles and Fatal Diseases
- Amyloidogenic Neurodegenerative Diseases: A Subset of Conformational Diseases
- Single-Molecule Analysis of Neurotoxic Proteins
- Molecular Dynamics Simulations of Amyloidogenesis by Neurotoxic Proteins
- Future Perspectives
- References
- Chapter 7. Reporters of Amyloid Structural Polymorphism
- Abstract
- Background and Rationale
- Ligand-Binding Phenotype
- Probes that Report their Conformation and Environment
- Assessing Pathology Spread and Quantification
- Applications and Implications of Polymorphism-Sensitive Reporters
- References
- Chapter 8. Conformation-Dependent Antibodies as Tools for Characterization of Amyloid Protein Aggregates
- Abstract
- Introduction
- Amyloid Fibrils and Oligomers have Defined, Unique Tertiary Structures and Molecular Polymorphisms that are Recognized by Conformation-Specific Antibodies
- Types of Conformation-Specific Antibodies Against Protein Aggregates
- Sequence-Specific Antibodies
- Sequence-Independent Antibodies
- Conformation-Specific Antibodies as Probes for Studying Protein Structure and Changes in Conformation Underlying Protein Aggregation
- Conformation-Specific Antibodies Recognize Polymorphism Within Amyloid Oligomers and Fibrils
- Conformation-Specific Antibodies as Probes for Studying Protein-Folding Mechanisms
- Therapeutic Applications of Conformation-Specific Antibodies in Neurodegenerative Diseases
- Conclusions
- References
- Chapter 2. Amyloid Fibril Length Quantification by Atomic Force Microscopy
- Part II: Nanoimaging and Nanotechnology of Aggregating Proteins: B. In Vivo Approaches
- Chapter 9. Analyzing Alzheimer’s Disease-Related Protein Deposition In Vivo By Multiphoton Laser Scanning Microscopy
- Abstract
- Protein Aggregation in Alzheimer’s Disease
- In Vivo Multiphoton Imaging
- Imaging Functional Changes Induced by AD-Related Pathology
- Limitations of In Vivo Multiphoton Imaging
- Conclusions
- References
- Chapter 10. Probing Amyloid Aggregation and Morphology In Situ by Multiparameter Imaging and Super-Resolution Fluorescence Microscopy
- Abstract
- Acknowledgments
- Introduction
- Multi-Parameter Microscopy of Protein Aggregation Kinetics
- Super-Resolution Imaging of Amyloid Aggregation
- Conclusion
- References
- Chapter 11. Imaging of Amyloid-β Aggregation Using a Novel Quantum dot Nanoprobe and its Advanced Applications
- Abstract
- Introduction of Amyloid-β Peptide Biology and Quantum dot Properties
- Preparation of the Quantum dot Nanoprobe
- In Vitro Imaging and Quantification of Aβ Aggregation
- Imaging of Aβ Behaviors in Live Cell Cultures
- High-Throughput Microscreening of Substances Inhibitory to Aβ Aggregation
- Current Problems and Future Possibilities of this Imaging Technology
- References
- Chapter 12. Studying the Molecular Determinants of Protein Oligomerization in Neurodegenerative Disorders by Bimolecular Fluorescence Complementation
- Abstract
- Acknowledgments
- Introduction
- Neurodegenerative Disorders and Protein Misfolding
- Protein Oligomerization, Aggregation and Toxicity
- Protein Complementation Assays: History and Latest Developments
- Advantages of BiFC Systems for Studying Protein Interactions
- Protein Complementation Assays for the Study of Neurodegenerative Disorders
- Methods
- References
- Chapter 13. Structure-Specific Intrinsic Fluorescence of Protein Amyloids Used to Study their Kinetics of Aggregation
- Abstract
- Acknowledgments
- Introduction
- Characterization of Oligomers Using Tryptophan and Tyrosine Fluorescence
- Certain Protein Crystals and Aggregates Develop Intrinsic Fluorescence in the Visible Range
- Intrinsic Fluorescence Arising from Disease-related Protein Amyloids During Aggregation
- Does the Intrinsic Fluorescence of Protein Amyloids Provide Novel Insights into their Remarkable Stability?
- Intrinsic Amyloid Fluorescence Informs on the Kinetics of Amyloid Formation and Mechanisms of Protein Misfolding Diseases
- Conclusions
- Future Work
- References
- Chapter 14. Real-Time Monitoring of Inclusion Formation in Living Zebrafish
- Abstract
- Introduction
- Zebrafish as a Model Organism
- Techniques for Generating Aggregation Models in Zebrafish
- Time-Lapse In Vivo Imaging Techniques
- Modeling Inclusion Formation in an HD Model in Zebrafish
- In Vivo Imaging of Inclusion Formation in Zebrafish
- Concluding Remarks and Outlook
- References
- Chapter 15. Scanning for Intensely Fluorescent Targets (SIFT) in the Study of Protein Aggregation at the Single-Particle Level
- Abstract
- The Role of Protein Aggregation in Neurodegeneration
- Measuring protein aggregation: from fibril formation to single-particle analysis
- The SIFT Method: Introduction and Technical Background
- Methods of Analysis
- Practical Applications
- Pitfalls and Common Misconceptions
- References
- Chapter 9. Analyzing Alzheimer’s Disease-Related Protein Deposition In Vivo By Multiphoton Laser Scanning Microscopy
- Part III: Polymorphism of Protein Misfolding and Aggregated Species
- Chapter 16. The Molecular Basis For TGFBIp-Related Corneal Dystrophies
- Abstract
- Acknowledgments
- Introduction
- Challenges in Understanding the Role of TGFBIp in Corneal Dystrophies
- Molecular Properties of TGFBIp: A Multidomain Protein with Four Homologous Domains
- TGFBIp and Corneal Dystrophy
- CD Mutations Induce Different TGFBIP Aggregation Mechanisms
- CD and Changes in Proteolytic Processing of TGFBIp
- TGFBIp Oligomerization
- TGFBIp and Macromolecular Interactions
- Aggregation Mechanism and Phenotypes
- Future Treatment
- References
- Chapter 17. Aβ Fibril Polymorphism and Alzheimer’s Disease
- Abstract
- Acknowledgments
- Alzheimer’s Disease: Relevance, Neuropathology and Etiology
- Cellular Formation and Chemical Variability of Aβ Peptide
- The Amyloid Hypothesis and the Putative Mechanism of Pathogenesis
- General Topology and Polymorphism of Aβ Fibrils
- Towards the Atomic Structures of Different Aβ Fibril Polymorphs
- The Molecular Basis of Aβ Fibril Polymorphism
- Biologic Relevance of Polymorphic Fibril Structures
- References
- Chapter 18. Structural Heterogeneity and Bioimaging of S100 Amyloid Assemblies
- Abstract
- Acknowledgments
- Introduction
- Structural Diversity of S100 Monomers and Multimers
- S100 Oligomers, Aggregates and Amyloids
- Bioimaging of S100 Amyloids by AFM and TEM
- Conclusions
- References
- Chapter 19. Polymorphism of Tau Fibrils
- Abstract
- Introduction
- Polymorphic Nature of Pathologic Tau Fibrils
- Factors Affecting the Morphology of Tau Fibrils
- A ‘Core’ Hypothesis for Generating Fibril Polymorphism
- Perspectives
- References
- Chapter 20. Amyloid-Like Protofibrils with Different Physical Properties
- Abstract
- Acknowledgments
- Introduction
- Protofibril Polymorphism
- Coexistence of Different Protofibril Populations
- Mechanical Properties of Protofibrils
- Concluding Remarks
- References
- Chapter 21. Insulin Oligomers: Detection, Characterization and Quantification Using Different Analytical Methods
- Abstract
- Introduction
- Spectroscopy
- Scattering Techniques
- Microscopy
- Separation Techniques
- Indirect Measurements
- Conclusions
- References
- Chapter 22. Imaging the Morphology and Structure of Apolipoprotein Amyloid Fibrils
- Abstract
- Introduction
- ApoA-I
- ApoE
- ApoC-II
- Structural Analysis of apoC-II Amyloid Fibrils
- Summary
- References
- Chapter 23. Polymorphism of Amyloid Fibrils and their Complexes with Catalase
- Abstract
- Introduction
- Catalase Interactions with Amyloid-β, Islet Amyloid Polypeptide and Prion Protein Fragments
- Binding of Catalase to Aβ, IAPP and PrP Fibrils
- The Shared Amyloid Catalase Recognition Sequence and Other Potential Amyloid Fibril Interactions
- Use of Catalase Binding to Amyloid Fibrils in Drug Discovery
- Conclusion
- References
- Chapter 24. On Possible Function and Toxicity of Multiple Oligomeric/Conformational States of a Globular Protein – Human Stefin B
- Abstract
- Acknowledgments
- Introduction
- Defining Intermediate States from which Amyloid Fibrils were Initiated
- Kinetic Model and Morphologies of Amyloid Fibril Formation
- Structural Data on Stefin Oligomers and the Role of Proline Isomerism
- Selective Interaction of the Tetramer of Stefin B with Aβ
- The Role of Copper
- Membrane Binding and Pore Formation
- Conclusions and Perspective
- References
- Chapter 25. Fibrillar Structures of Yeast Prion Sup35 In Vivo
- Abstract
- Introduction
- Yeast Prion Sup35 as a Model Amyloid-Forming Protein in Cells
- In Vitro Fibril Formation of Sup35
- Structures of Sup35 Amyloids in Yeast Cells
- Dynamic Properties of Sup35 Amyloids in Living Yeast Cells
- Concluding Remarks
- References
- Chapter 26. Glycosaminoglycans and Fibrillar Polymorphism
- Abstract
- Acknowledgments
- Introduction
- Proteoglycan Components Responsible for Protein Binding and Fibril Enhancement
- The Polymeric Nature of GAGs is Important for Inducing Mature Amyloid Fibrils
- GAGs Affect Fibril Morphology in Different Ways
- Specificity of GAG–Protein Interactions
- GAGs can Induce Fibrils in Non-Amyloidogenic Proteins
- GAGs can Accelerate Fibrillation by Binding Monomers or by Interacting with Oligomers
- Future Perspectives and Challenges: the Importance of Molecular Insights
- References
- Chapter 27. Dopamine-Induced α-Synuclein Oligomers
- Abstract
- The Role of Dopamine in a Healthy Brain and in Parkinson’s Disease
- α-Synuclein:DA Oligomers – Discovery and Properties
- Shape and Structure of α-syn:DA Oligomers
- How Does DA Link α-syn Molecules?
- How Does DA Inhibit α-Synuclein Fibril Formation?
- Biologic Significance of α-syn:DA Oligomers
- References
- Chapter 28. The Formation of Amyloid-Like Superstructures: On the Growth of Amyloid Spherulites
- Abstract
- Acknowledgments
- Large-Scale Polymorphism in Protein Aggregation
- Amyloid Spherulites: Hypotheses on the Structural Arrangement
- Factors Affecting the Formation of Insulin Amyloid Spherulites
- Conclusions and Perspectives
- References
- Chapter 29. Characterizing Nanoscale Morphologic and Mechanical Properties of α-Synuclein Amyloid Fibrils with Atomic Force Microscopy
- Abstract
- Introduction
- aS Fibrils on Different Solid Surfaces
- Preparation of Supported Lipid Bilayers on Mica
- α-Synuclein Monomers on Supported Bilayers
- α-Synuclein Fibrils on POPC-Supported Bilayers
- Inferring the Mechanical Properties of Fibrils from Images
- Wild-Type Fibrils on a POPC–POPG Supported Bilayer
- Conclusions
- Materials and Methods
- References
- Chapter 30. Polymorphism in Casein Protein Aggregation and Amyloid Fibril Formation
- Abstract
- Acknowledgments
- Introduction to the Casein Proteins
- Amorphous Aggregation Properties of Casein Proteins Under Native Conditions
- Amyloid Fibril Formation by κ- and αs2-Casein Proteins
- Modification and Inhibition of κ- and αs2-Casein Amyloid Fibril Formation by β- and αs1-Caseins
- Potential Bio-Nanomaterial Applications of Casein Amyloid Fibrils
- Conclusions
- References
- Chapter 31. Structural Basis for the Polymorphism of β-Lactoglobulin Amyloid-Like Fibrils
- Abstract
- Acknowledgments
- Why β-Lactoglobulin?
- Formation Mechanisms of Amyloid-Like Fibrils From β-Lactoglobulin
- Polymorphism of β-Lactoglobulin Amyloids: Rod-Like, Worm-Like and Straight Fibrils
- Molecular Structure of Amyloid Fibrils
- Conclusions
- References
- Chapter 32. Fibrillation and Polymorphism of Human Serum Albumin
- Abstract
- Introduction
- The Origin of Protein Misfolding
- The Fibrillation Process of Human Serum Albumin
- Conclusions and Outlook
- References
- Chapter 33. Formation of α-Helix-Based Twisted Ribbon-Like Fibrils from Ionic-Complementary Peptides
- Abstract
- Acknowledgments
- Introduction
- EMK8-II with Protected Terminus Forms Twisted Ribbon-Like Fibrils
- Structural Characteristics of EMK8-II Fibrils
- Assembly Dynamics of EMK8-II Fibrils
- Cooperative Balance of Hydrophobicity and Ionic Interactions
- The Assembly Mechanism of α-Helix-Based Fibrils
- References
- Chapter 34. Polymorphism, Metastable Species and Interconversion: The Many States of Glucagon Fibrils
- Abstract
- Acknowledgments
- Introduction
- The Basis of Fibril Polymorphism: Different Protofilament Packing and/or Different Protofilaments
- How to Obtain Different Types of Glucagon Fibril: An Overview of the Current Literature
- A Time-Resolved SAXS Study of the Effect of Shaking on Fibrillation and Fibril Structure: Different Degrees of Protofilament Association Under Quiescent and Shaking Conditions
- Interconversion Between Fibril Morphologies: Metastable Fibril States Destabilized by Elevated Temperatures
- Hydration and Packing Modulate Fibrillation and Fibril Stability
- Inhibition of Glucagon Fibrillation by Modified Cyclodextrins
- Perspectives: Stable or Unstable Fibrils in vivo?
- References
- Chapter 16. The Molecular Basis For TGFBIp-Related Corneal Dystrophies
- Part IV: Polymorphism of Protein Misfolding and Aggregation Processes
- Chapter 35. Multiple Pathways of Lysozyme Aggregation
- Abstract
- Introduction
- Polymorphism of Amyloid Intermediates and Multiple Assembly Pathways
- Characterizing Lysozyme Assembly Pathways and their Respective Intermediates with Atomic Force Microscopy
- Physical Characterization of Transient Intermediates
- Conclusions and Discussion
- References
- Chapter 36. Structure–Function Studies of Amyloid Pores in Alzheimer’s Disease as a Case Example of Neurodegenerative Diseases
- Abstract
- Acknowledgments
- General Properties of Amyloids
- Amyloids in Alzheimer’s Disease
- Interaction of Peptides With the Cell Membrane
- Pore Hypothesis
- Structural and Functional Studies of Amyloid Pores
- Alternative Mechanisms
- References
- Chapter 37. Nanoscale Optical Imaging of Protein Amyloids
- Abstract
- Acknowledgments
- Introduction
- Structural Biology of Amyloids
- Nanoscale Biophysics of Amyloid Fibrils Using Super-Resolution Optical Imaging
- Conclusions And Future Projections
- References
- Chapter 38. Assembly of Amyloid β-Protein Variants Containing Familial Alzheimer’s Disease-Linked Amino Acid Substitutions
- Abstract
- Acknowledgments
- Introduction: ‘Minor’ Changes have Major Effects
- Point Mutations Affecting the Aβ Sequence
- Conclusions
- References
- Chapter 39. Role of Aberrant α-Synuclein–Membrane Interactions in Parkinson’s Disease
- Abstract
- Introduction
- Evidence for Membrane-Induced α-Syn Self-Assembly
- Conformations of α-Syn at the Membrane Surface
- A Role for Aberrant α-Syn–Membrane Interactions in Neurotoxicity
- Concluding Remarks
- References
- Chapter 40. ELOA – Equine Lysozyme Complexes with Oleic Acid: Structure and Cytotoxicity Studied by Bio-Imaging Techniques
- Abstract
- Acknowledgments
- Introduction
- HAMLET: Occurrence in Vivo and in Vitro
- Structural Similarity of EL and α-LactalbuminS
- The Production of HAMLET-type complexes
- Protein Conformation in ELOA
- ELOA Oligomeric Structure
- ELOA Interaction With Lipid Bilayers
- ELOA Cellular Toxicity
- Conclusions
- References
- Chapter 41. Structure of a Misfolded Intermediate of a PDZ Domain
- Abstract
- Acknowledgments
- Introduction
- Results
- Conclusions
- References
- Chapter 42. Intranuclear Amyloid – Local and Quantitative Analysis of Protein Fibrillation in the Cell Nucleus
- Abstract
- Acknowledgments
- Disease-Associated Protein Fibrillation
- Functional Amyloid
- Characterization of nuclear protein fibrillation
- Conclusions
- References
- Chapter 43. Conversion of α-Helical Proteins into an Alternative β-Amyloid Fibril Conformation
- Abstract
- Introduction to the Fibril Field
- Transition of α-Helical Proteins into Amyloid-Like Fibrils
- Polymorphism of Fibrillar Species Associated with α-Helical Proteins
- Future Perspectives
- References
- Chapter 44. The Effect of Shear Flow on Amyloid Fibril Formation and Morphology
- Abstract
- Introduction
- Shear Flow and Protein Misfolding
- Effect of Shear Flow on Fibril Formation
- Observed Structures: Impact of Flow on Fibril Structure and Mechanics
- Conclusions
- References
- Chapter 35. Multiple Pathways of Lysozyme Aggregation
- Subject Index
- Name Index
- Edition: 1
- Published: November 5, 2013
- Imprint: Academic Press
- No. of pages: 552
- Language: English
- Hardback ISBN: 9780123944313
- eBook ISBN: 9780123978219
VU
Vladimir N Uversky
Prof. Vladimir N. Uversky, PhD, DSc, FRSB, FRSC, F.A.I.M.B.E., Professor at the Department of Molecular Medicine, Morsani College of Medicine, University of South Florida (USF), is a pioneer in the field of protein intrinsic disorder. He has made a number of groundbreaking contributions in the field of protein folding, misfolding, and intrinsic disorder. He obtained his academic degrees from Moscow Institute of Physics and Technology (Ph.D., in 1991) and from the Institute of Experimental and Theoretical Biophysics, Russian Academy of Sciences (D.Sc., in 1998). He spent his early career working mostly on protein folding at the Institute of Protein Research and the Institute for Biological Instrumentation (Russia). In 1998, moved to the University of California Santa Cruz. In 2004, joined the Indiana University−Purdue University Indianapolis as a Senior Research Professor. Since 2010, Professor Uversky is with USF, where he works on various aspects of protein intrinsic disorder phenomenon and on analysis of protein folding and misfolding processes. Prof. Uversky has authored over 1250 scientific publications and edited several books and book series on protein structure, function, folding, misfolding, and intrinsic disorder. He is also serving as an editor in a number of scientific journals. He was a co-founder of the Intrinsically Disordered Proteins Subgroup at the Biophysical Society and the Intrinsically Disordered Proteins Gordon Research Conference. Prof. Uversky collaborated with more than 12,500 colleagues from more than 2,750 research organizations in 89 countries/territories.
Affiliations and expertise
Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesRead Bio-nanoimaging on ScienceDirect