Nanotechnology: 5 Nanomedicine
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Wiley-VCH
2009
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| adam_text | Contents
List of Contributors XV
Part One Nanomedicine: The Next Waves of Medical Innovations
1
1
Introduction
3
Viola
Vogel
1.1
Great Hopes and Expectations are Colliding with Wild Hype and
Some Fantasies
3
1.2
The First Medical Applications are Coming to the Patients Bedside
4
1.3
Major Advances in Medicine Have Always been Driven by New
Technologies
5
1.4
Nanotechnologies Foster an Explosion of New Quantitative
Information How Biological Nanosystems Work
6
1.5
Insights Gained from Quantifying how the Cellular Machinery
Works will lead to Totally New Ways of Diagnosing and Treating
Disease
7
1.6
Engineering Cell Functions with Nanoscale Precision
8
1.7
Advancing Regenerative Medicine Therapies
8
1.8
Many More Relevant Medical Fields Will be Innovated by
Nanotechnologies
9
References
10
Part Two Imaging, Diagnostics and Disease Treatment by Using Engineered
Nanoparticles
17
2
From In Vivo Ultrasound and
MRI
Imaging to Therapy: Contrast
Agents Based on Target-Specific Nanoparticles
19
Kirk D. Wallace, Michael S. Hughes, Jon
N.
Marsh, Shelton D. Caruthers,
Gregory M. Lanza, and Samuel A.
Wickline
2.1
Introduction
19
2.2
Active versus Passive Approaches to Contrast Agent Targeting
20
2.3
Principles of Magnetic Resonance Contrast Agents
21
VI
Contents
2.3.1
Mathematics of
Signal
Contrast
22
2.3.2
Perfluorocarbon Nanoparticles for Enhancing Magnetic Resonance
Contrast
23
2.3.3
Perfluorocarbon Nanoparticles for Fluorine (19F) Imaging
and Spectroscopy
24
2.3.4
Fibrin-Imaging for the Detection of Unstable Plaque and
Thrombus
25
2.3.5
Detection of Angiogenesis and Vascular Injury
27
2.4
Perfluorocarbon Nanoparticles as an Ultrasound Contrast Agent
31
2.4.1
Entropy-Based Approach
33
2.4.2
The Density Function w^y)
33
2.4.3
Ultrasound in a Precancerous Animal Model
34
2.4.3.1
Image Analysis
36
2.4.4
Targeting of MDA-435 Tumors
38
2.4.5
In Vivo Tumor Imaging at Clinical Frequencies
42
2.5
Contact-Facilitated Drug Delivery and Radiation Forces
43
2.5.1
Primary and Secondary Radiation Forces
43
2.5.2
In Vitro Results
44
2.6
Conclusions
46
References
47
3
Nanoparticles for Cancer Detection and Therapy
51
Bicma
Codin, Rita E.
Serda, Jason Sakamoto, Paolo Decuzzi, and
Mauro
Ferrari
3.1
Introduction
51
3.1.1
Cancer Physiology and Associated Biological Barriers
51
3.1.2
Currently Used
Anticancer
Agents
53
3.1.2.1
Chemotherapy
54
3.1.2.2
Anti-Angiogenic Therapeutics
54
3.1.2.3
Immunoťherapy
55
3.1.2.4
Issues and Challenges
56
3.2
Nanotedmology for Cancer Applications: Basic Definitions and
Rationale for Use
57
3.3
First-Generation Nanovectors and their History of Clinical Use
59
3.4
Second-Generation Nanovectors: Achieving Multiple Functionality
at the Single Particle Level
62
3.5
Third-Generation Nanoparticles: Achieving Collaborative Interactions
Among Different Nanopartkle Families
65
3.6
Nanovector Mathematics and Engineering
69
3.7
The Biology, Chemistry and Physics of Nanovector
Characterization
75
3.7.1
Physical Characterization
76
3.7.2
in Vitro Testing
76
3.7.2.1
in Vitro
Toxicity
Testing
79
3.7.3
In Vivo Animal Testing
79
Contents
VII
3.8
A Compendium of Unresolved Issues
79
References
82
Part Three Imaging and Probing the Inner World of Cells
89
4
Electron Cryomicroscopy of Molecular Nanomachines and Cells
91
Matthew
L
Baker, Michael P. Marsh, and Wah
Chiu
4.1
Introduction
91
4.2
Structure Determination of Nanomachines and Cells
92
4.2.1
Experimental Procedures in Cryo-EM and Cryo-ET
92
4.2.1.1
Specimen Preparation for Nanomachines and Cells
92
4.2.1.2
Cryo-Specimen Preservation
94
4.2.1.3
Low-Dose Imaging
95
4.2.1.4
Image Acquisition
95
4.2.2
Computational Procedures in Cryo-EM and Cryo-ET
95
4.2.2.1
Image Processing and Reconstruction
96
4.2.2.2
Structure Analysis and Data Mining
97
4.2.3
Data Archival
98
4.3
Biological Examples
98
4.3.1
Skeletal Muscle Calcium Release Channel
99
4.3.2
Bacteriophage Epsilonl5
100
4.3.3
Bacterial Flagellum
101
4.3.4
Proteomic Atlas
102
4.4
Future Prospects
103
References
104
5
Pushing Optical Microscopy to the Limit From Single-Molecule
Fluorescence Microscopy to Label-Free Detection and Tracking
of Biological Nano-Objects
113
Philipp Kukura,
Alois
Renn,
and Wahid Sandoghdar
5.1
Introduction
113
5.1.1
Linear Contrast Mechanisms
114
5.1.2
Nonlinear Contrast Mechanisms
117
5.2
Single-Molecule Fluorescence Detection: Techniques and
Applications
117
5.2.1
Single Molecules: light Sources with Ticks
118
5.2.2
The Signal-to-Noise Ratio Challenge
119
5.2.3
High-Precision Localization and Tracking of Single Emitters
120
5.2.4
Getting Around the Rayleigh limit: Colocalization of Multiple
Emitters
123
5.3
Detection of Non-Fluorescent Single Nano-Objects
127
5.3.1
The Difficulty of Detecting Small Particles Through Light
Scattering
127
5.3.2
Interferometrie
Detection of Gold Nanoparticles
228
Vili
Contents
5.3.2.1
Is it Possible to Detect Molecule-Sized Labels?
131
5.3.2.2
The Needle in the Haystack: Finding and Identifying Gold
132
5.3.3
Combining Scattering and Fluorescence Detection: A Long-Range
Nanoscopic Ruler
132
5.3.4
Label-Free Detection of Biological Nano-Objects
134
5.4
Summary and Outlook
137
References
138
6
Nanostructured Probes for In
Vivo Cene
Detection
143
Gang
Bao,
Phillip Santangelo, Nitin Nitin, and Won Jong Rhee
6.1
Introduction
143
6.2
Fluorescent Probes for live-Cell
RNA
Detection
145
6.2.1
Tagged Linear ODN Probes
145
6.2.2
ODN Hairpin Probes
146
6.2.3
Fluorescent Protein-Based Probes
150
6.3
Probe Design and Structure-Function Relationships
151
6.3.1
Target Specificity
151
6.3.2
Molecular Beacon Structure-Function Relationships
152
6.3.3
Target Accessibility
153
6.3.4
Fluorophores and Quenchers
254
6.4
Cellular Delivery of Nanoprobes
155
6.5
Living Cell
RNA
Detection Using Nanostructured Probes
158
6.5.1
Biological Significance
159
6.6
Engineering Challenges in New Probe Development
161
References
163
7
High-Content Analysis of Cytoskeleton Functions by Fluorescent
Speckle Microscopy
167
Kathryn T.
Applegate,
Ce
Yang, and Caudenz
Danuser
7.1
Introduction
267
7.2
Cell Morphological Activities and Disease
168
7.2.1
Cell Migration
268
7.2.2
Cell Division
169
7.2.3
Response to Environmental Changes
270
7.2.4
Cell-Cell Communication
170
7.3
Principles of Fluorescent Speckle Microscopy (FSM)
272
7.4
Speckle Image Formation
172
7.4.1
Speckle Formation in Microtubules (MTs): Stochastic Clustering of
Labeled Tubulin Dimers in the MT Lattice
272
7.4.2
Speckle Formation in Other Systems: The Platform Model
274
7.5
Interpretation of Speckle Appearance and Disappearance
275
7.5.1
Naive Interpretation of Speckle Dynamics
275
7.5.2
Computational Models of Speckle Dynamics
275
7.5.3
Statistical Analysis of Speckle Dynamics
277
Contents
IX
7.5.4 Single- and Multi-Fluorophore
Speckles Reveal Different Aspects of the
Architectural Dynamics of Cytoskeleton Structures
179
7.6
Imaging Requirements for FSM
180
7.7
Analysis of Speckle Motion
181
7.7.1
Tracking Speckle Flow: Early and Recent Developments
181
7.7.2
Tracking Single-Speckle Trajectories
183
7.7.3
Mapping Polymer Turnover Without Speckle Trajectories
185
7.8
Applications of FSM for Studying Protein Dynamics In Vitro and
In Vivo
185
7.9
Results from Studying Cytoskeleton Dynamics
192
7.9.1
F-Actin in Cell Migration
192
7.9.1.1
F-Actin in Epithelial Cells is Organized Into Four Dynamically
Distinct Regions
192
7.9.1.2
Actin Disassembly and Contraction are Coupled in the Convergence
Zone
193
7.9.1.3
Two Distinct F-Actin Structures Overlap at the Leading Edge
193
7.9.2
Architecture of Xenopus laevis Egg Extract Meiotic Spindles
194
7.9.2.1
Individual MTs within the Same Bundle Move at Different Speeds
195
7.9.2.2
The Mean Length of Spindle MTs is
40%
of the Total Spindle
Length
195
7.9.3
Hierarchical Transmission of F-Actin Motion Through Focal
Adhesions
199
7.10
Outlook: Speckle Fluctuation Analysis to Probe Material
Properties
200
7.11
Conclusions
202
References
203
8
Harnessing Biological Motors to Engineer Systems for Nanoscale
Transport and Assembly
207
Anita Goel and Viola
Vogel
8.1
Sequential Assembly and Polymerization
207
8.1.1
Engineering Principle No.
1:
discrimination of similar building
blocks
209
8.2
Cargo Transport
210
8.2.1
Engineering Principle No.
2:
various track designs
212
8.3
Cargo Selection
215
8.3.1
Engineering Principle No.
3:
barcoding
215
8.3.2
Engineering Principle No.
4:
active transport of tailored drugs and
gene carriers
218
8.4
Quality Control
218
8.4.1
Engineering Principle No.
5:
error recognition and repair at the
molecular level
219
8.4.2
Engineering Principle No.
6:
error recognition and repair at the
system level
220
8.5
External Control
220
Contents
8.5.1 Engineering
Principle No.
7:
performance regulation on demand
220
8.6
Concluding Remarks
223
References
225
Part Four Innovative Disease Treatments and Regenerative Medicine
233
9
Mechanical Forces Matter in Health and Disease:
From Cancer to Tissue Engineering
235
Viola
Vogel
and Michael P. Sheetz
9.1
Introduction: Mechanical Forces and Medical Indications
235
9.2
Force-Bearing Protein Networks Hold the Tissue Together
237
9.2.1
Cell-Cell Junctions
237
9.2.2
Cell-Matrix Junctions
238
9.3
Nanotechnology has Opened a new Era in Protein Research
241
9.3.1
Mechanochemical Signal Conversion and
Mechanotransduction
241
9.3.2
Mechanical Forces and Structure-Function Relationships
242
9.4
Making the Very First Contacts
244
9.4.1
Molecular Players of Cell-Extracellular Matrix Junctions
244
9.4.1.1
Fibronectin
245
9.4.1.2
Integrins
246
9.4.1.3
Talin
247
9.4.1.4
Other Scaffolding Proteins that Provide a Linkage Between
Integrins
and F-Actin
250
9.4.1.5
Cell Cytoskeleton
250
9.5
Force-Upregulated Maturation of Early Cell-Matrix Adhesions
250
9.5.1
Protein Stretching Plays a Central Role
250
9.5.1.1
Vinculin is Recruited to Stretched Talin in a Force-dependent
Manner
251
9.6
Cell Signaling by Force-Upregulated Phosphorylation of Stretched
Proteins
252
9.6.1
Phosphorylation is Central to Regulating Cell Phenotypes
252
9.6.1.1
Stretch-Dependent Binding of Some Cytoplasmic Proteins to
Cytoskeletons
254
9.6.1.2
Tyrosine Phosphorylation as a General Mechanism of Force
Sensing
255
9.7
Dynamic Interplay between the Assembly and Disassembly of
Adhesion Sites
257
9.7.1
Molecular Players of the Adhesome
257
9.8
Forces that Cells Apply to Mature Cell-Matrix and Cell-Cell
Junctions
261
9.8.1
Insights Obtained from Micro- and Nanofabricated Tools
26Í
9.9
Sensing Matrix Rigidity
263
9.9.1
Reciprocity of the Physical Aspects of the Extracellular Matrix
and Intracellular Events
263
Contents
XI
9.9.1.1
Time Dependence and Rigidity Responses
266
9.9.1.2
Position and Spacing Dependence of the Rigidity Responses
267
9.10
Cellular Response to Initial Matrix Conditions
269
9.10.1
Assembly, Stretching and Remodeling of the Extracellular
Matrix
269
9.10.1.1
Switching the Biochemistry Displayed by the Matrix by Stretching
and Unfolding of Matrix Proteins
270
9.10.1.2
Cell Responses to Initial
Biomaterial
Properties and Later to
Self-Made Extracellular Matrix
273
9.11
Cell Motility in Response to Force Generation and Matrix
Properties
275
9.12
Mechanical Forces and Force Sensing in Development and
Disease
276
9.12.1
Cancer and Cell Transformation
277
9.12.2
Angiogenesis
279
9.12.3
Tissue Engineering
280
References
284
10
Stem Cells and Nanomedicine: Nanomechanics of the
Microenvironment 305
Florian
Rehfeldt, Adam
J.
Engler,
and Dennis E. Discher
10.1
Introduction
305
10.2
Stem Cells in
Microenvironment 305
10.2.1
Adult Stem Cells
305
10.2.2
Probing the Nanoelasticity of Cell
Microenvironments 308
10.2.3
Physical Properties of Ex-Vivo
Microenvironments 311
10.3
In Vitro
Microenvironments 312
10.3.1
Cells Probe and Feel their Mechanical
Microenvironment 313
10.3.2
Cells React to External Forces
315
10.3.3
Adult Stem Cell Differentiation
316
10.3.4
Implications for Regenerative Medicine
318
10.4
Future Perspectives
329
References
320
11
The Micro- and Nanoscale Architecture of the Immunological
Synapse
323
lain E. Dunlop, Michael
L
Dustin,
and Joachim P.
Spatz
11.1
Introduction
323
11.2
The Immunological Synapse
325
11.2.1
Large-Scale Structure and Supramolecular Activation Clusters
(SMACs)
325
11.2.2
TCR-p-MHC Microclusters as Important Signaling Centers
329
11.3
The Smallest Activating Units? p-MHC
Oligomers
331
11.4
Molecular-Scale Nanolithography
334
11.4.1
Block Copolymer Micellar Nanolithography
334
XII Contents
11.4.2
Micronanopatterning by Combining Block Copolymer Micellar
Nanolithography and Electron-Beam lithography
337
11.5
Therapeutic Possibilities of Immune Synapse Micro- and
Nanolithography
338
11.6
Conclusions
340
References
341
12
Bone Nanostructure and its Relevance for Mechanical Performance,
Disease and Treatment
345
Peter Fratzl, Himadri S.
Capta,
Paul Roschger, and Klaus Klaushofer
12.1
Introduction
345
12.2
Nanoscale Structure of Bone
346
12.3
Mechanical Behavior of Bone at the Nanoscale
347
12.4
Bone Mineral Density Distribution in Osteoporosis and
Treatments
349
12.4.1
Osteoporosis
351
12.5
Examples of Disorders Affecting the Structure of Bone Material
352
12.5.1
Osteogenesis
Imperfecta
352
12.5.2
Pycnodysostosis
353
12.5.3
Fluorosis
354
12.6
Conclusions
355
References
357
1
3
Nanoengineered Systems for Tissue Engineering and Regeneration
361
AH Khademhosseini, Bimal Rajalingam, Satoshijinno, and Robert
Langer
13.1
Introduction
361
13.2
Nanomaterials Synthesized Using Top-Down Approaches
362
13.2.1
Electrospinning Nanofibers
363
13.2.2
Scaffolds with Nanogrooved Surfaces
365
13.3
Nanomaterials Synthesized using Bottom-Up Approaches
367
13.3.1
Self-Assembled
Peptide
Scaffolds
367
13.3.2
Layer-by-Layer Deposition of Nanomaterials
367
13.3.3
Carbon Nanotubes
370
13.3.4
MRI
Contrast Agents
371
13.3.5
Quantum Dots
373
13.4
Future Directions
374
13.5
Conclusions
376
References
376
14
Self-Assembling Peptide-Based Nanostructures for Regenerative
Medicine
385
Ramille M.
Capito,
Alvaro Mata,
and Samuel I. Stupp
14.1
Introduction
385
14.2
Self-Assembling Synthetic
Peptide
Scaffolds
387
14.2.1 ß-Sheet Peptides 387
Contents XJII
14.2.2 ß-Hairpin Peptides 389
14.2.3 Block Copolypeptides 391
14.2.4
Ionic Self-Complementary
Peptides 392
14.2.5 Fmoc Peptides 393
14.2.6
Peptide Amphiphiles
394
14.3
Self-Assembling
Systems
for Surface Modification
401
14.3.1
Coatings on Surfaces
401
14.3.2
Coatings on
3-D
Scaffolds
406
ХАЛ
Clinical Potential of Self-Assembling Systems
407
14.5
Conclusions
408
References
409
Index
413
|
| adam_txt |
Contents
List of Contributors XV
Part One Nanomedicine: The Next Waves of Medical Innovations
1
1
Introduction
3
Viola
Vogel
1.1
Great Hopes and Expectations are Colliding with Wild Hype and
Some Fantasies
3
1.2
The First Medical Applications are Coming to the Patients' Bedside
4
1.3
Major Advances in Medicine Have Always been Driven by New
Technologies
5
1.4
Nanotechnologies Foster an Explosion of New Quantitative
Information How Biological Nanosystems Work
6
1.5
Insights Gained from Quantifying how the Cellular Machinery
Works will lead to Totally New Ways of Diagnosing and Treating
Disease
7
1.6
Engineering Cell Functions with Nanoscale Precision
8
1.7
Advancing Regenerative Medicine Therapies
8
1.8
Many More Relevant Medical Fields Will be Innovated by
Nanotechnologies
9
References
10
Part Two Imaging, Diagnostics and Disease Treatment by Using Engineered
Nanoparticles
17
2
From In Vivo Ultrasound and
MRI
Imaging to Therapy: Contrast
Agents Based on Target-Specific Nanoparticles
19
Kirk D. Wallace, Michael S. Hughes, Jon
N.
Marsh, Shelton D. Caruthers,
Gregory M. Lanza, and Samuel A.
Wickline
2.1
Introduction
19
2.2
Active versus Passive Approaches to Contrast Agent Targeting
20
2.3
Principles of Magnetic Resonance Contrast Agents
21
VI
Contents
2.3.1
Mathematics of
Signal
Contrast
22
2.3.2
Perfluorocarbon Nanoparticles for Enhancing Magnetic Resonance
Contrast
23
2.3.3
Perfluorocarbon Nanoparticles for Fluorine (19F) Imaging
and Spectroscopy
24
2.3.4
Fibrin-Imaging for the Detection of Unstable Plaque and
Thrombus
25
2.3.5
Detection of Angiogenesis and Vascular Injury
27
2.4
Perfluorocarbon Nanoparticles as an Ultrasound Contrast Agent
31
2.4.1
Entropy-Based Approach
33
2.4.2
The Density Function w^y)
33
2.4.3
Ultrasound in a Precancerous Animal Model
34
2.4.3.1
Image Analysis
36
2.4.4
Targeting of MDA-435 Tumors
38
2.4.5
In Vivo Tumor Imaging at Clinical Frequencies
42
2.5
Contact-Facilitated Drug Delivery and Radiation Forces
43
2.5.1
Primary and Secondary Radiation Forces
43
2.5.2
In Vitro Results
44
2.6
Conclusions
46
References
47
3
Nanoparticles for Cancer Detection and Therapy
51
Bicma
Codin, Rita E.
Serda, Jason Sakamoto, Paolo Decuzzi, and
Mauro
Ferrari
3.1
Introduction
51
3.1.1
Cancer Physiology and Associated Biological Barriers
51
3.1.2
Currently Used
Anticancer
Agents
53
3.1.2.1
Chemotherapy
54
3.1.2.2
Anti-Angiogenic Therapeutics
54
3.1.2.3
Immunoťherapy
55
3.1.2.4
Issues and Challenges
56
3.2
Nanotedmology for Cancer Applications: Basic Definitions and
Rationale for Use
57
3.3
First-Generation Nanovectors and their History of Clinical Use
59
3.4
Second-Generation Nanovectors: Achieving Multiple Functionality
at the Single Particle Level
62
3.5
Third-Generation Nanoparticles: Achieving Collaborative Interactions
Among Different Nanopartkle Families
65
3.6
Nanovector Mathematics and Engineering
69
3.7
The Biology, Chemistry and Physics of Nanovector
Characterization
75
3.7.1
Physical Characterization
76
3.7.2
in Vitro Testing
76
3.7.2.1
in Vitro
Toxicity
Testing
79
3.7.3
In Vivo Animal Testing
79
Contents
VII
3.8
A Compendium of Unresolved Issues
79
References
82
Part Three Imaging and Probing the Inner World of Cells
89
4
Electron Cryomicroscopy of Molecular Nanomachines and Cells
91
Matthew
L
Baker, Michael P. Marsh, and Wah
Chiu
4.1
Introduction
91
4.2
Structure Determination of Nanomachines and Cells
92
4.2.1
Experimental Procedures in Cryo-EM and Cryo-ET
92
4.2.1.1
Specimen Preparation for Nanomachines and Cells
92
4.2.1.2
Cryo-Specimen Preservation
94
4.2.1.3
Low-Dose Imaging
95
4.2.1.4
Image Acquisition
95
4.2.2
Computational Procedures in Cryo-EM and Cryo-ET
95
4.2.2.1
Image Processing and Reconstruction
96
4.2.2.2
Structure Analysis and Data Mining
97
4.2.3
Data Archival
98
4.3
Biological Examples
98
4.3.1
Skeletal Muscle Calcium Release Channel
99
4.3.2
Bacteriophage Epsilonl5
100
4.3.3
Bacterial Flagellum
101
4.3.4
Proteomic Atlas
102
4.4
Future Prospects
103
References
104
5
Pushing Optical Microscopy to the Limit From Single-Molecule
Fluorescence Microscopy to Label-Free Detection and Tracking
of Biological Nano-Objects
113
Philipp Kukura,
Alois
Renn,
and Wahid Sandoghdar
5.1
Introduction
113
5.1.1
Linear Contrast Mechanisms
114
5.1.2
Nonlinear Contrast Mechanisms
117
5.2
Single-Molecule Fluorescence Detection: Techniques and
Applications
117
5.2.1
Single Molecules: light Sources with Ticks
118
5.2.2
The Signal-to-Noise Ratio Challenge
119
5.2.3
High-Precision Localization and Tracking of Single Emitters
120
5.2.4
Getting Around the Rayleigh limit: Colocalization of Multiple
Emitters
123
5.3
Detection of Non-Fluorescent Single Nano-Objects
127
5.3.1
The Difficulty of Detecting Small Particles Through Light
Scattering
127
5.3.2
Interferometrie
Detection of Gold Nanoparticles
228
Vili
Contents
5.3.2.1
Is it Possible to Detect Molecule-Sized Labels?
131
5.3.2.2
The Needle in the Haystack: Finding and Identifying Gold
132
5.3.3
Combining Scattering and Fluorescence Detection: A Long-Range
Nanoscopic Ruler
132
5.3.4
Label-Free Detection of Biological Nano-Objects
134
5.4
Summary and Outlook
137
References
138
6
Nanostructured Probes for In
Vivo Cene
Detection
143
Gang
Bao,
Phillip Santangelo, Nitin Nitin, and Won Jong Rhee
6.1
Introduction
143
6.2
Fluorescent Probes for live-Cell
RNA
Detection
145
6.2.1
Tagged Linear ODN Probes
145
6.2.2
ODN Hairpin Probes
146
6.2.3
Fluorescent Protein-Based Probes
150
6.3
Probe Design and Structure-Function Relationships
151
6.3.1
Target Specificity
151
6.3.2
Molecular Beacon Structure-Function Relationships
152
6.3.3
Target Accessibility
153
6.3.4
Fluorophores and Quenchers
254
6.4
Cellular Delivery of Nanoprobes
155
6.5
Living Cell
RNA
Detection Using Nanostructured Probes
158
6.5.1
Biological Significance
159
6.6
Engineering Challenges in New Probe Development
161
References
163
7
High-Content Analysis of Cytoskeleton Functions by Fluorescent
Speckle Microscopy
167
Kathryn T.
Applegate,
Ce
Yang, and Caudenz
Danuser
7.1
Introduction
267
7.2
Cell Morphological Activities and Disease
168
7.2.1
Cell Migration
268
7.2.2
Cell Division
169
7.2.3
Response to Environmental Changes
270
7.2.4
Cell-Cell Communication
170
7.3
Principles of Fluorescent Speckle Microscopy (FSM)
272
7.4
Speckle Image Formation
172
7.4.1
Speckle Formation in Microtubules (MTs): Stochastic Clustering of
Labeled Tubulin Dimers in the MT Lattice
272
7.4.2
Speckle Formation in Other Systems: The Platform Model
274
7.5
Interpretation of Speckle Appearance and Disappearance
275
7.5.1
Naive Interpretation of Speckle Dynamics
275
7.5.2
Computational Models of Speckle Dynamics
275
7.5.3
Statistical Analysis of Speckle Dynamics
277
Contents
IX
7.5.4 Single- and Multi-Fluorophore
Speckles Reveal Different Aspects of the
Architectural Dynamics of Cytoskeleton Structures
179
7.6
Imaging Requirements for FSM
180
7.7
Analysis of Speckle Motion
181
7.7.1
Tracking Speckle Flow: Early and Recent Developments
181
7.7.2
Tracking Single-Speckle Trajectories
183
7.7.3
Mapping Polymer Turnover Without Speckle Trajectories
185
7.8
Applications of FSM for Studying Protein Dynamics In Vitro and
In Vivo
185
7.9
Results from Studying Cytoskeleton Dynamics
192
7.9.1
F-Actin in Cell Migration
192
7.9.1.1
F-Actin in Epithelial Cells is Organized Into Four Dynamically
Distinct Regions
192
7.9.1.2
Actin Disassembly and Contraction are Coupled in the Convergence
Zone
193
7.9.1.3
Two Distinct F-Actin Structures Overlap at the Leading Edge
193
7.9.2
Architecture of Xenopus laevis Egg Extract Meiotic Spindles
194
7.9.2.1
Individual MTs within the Same Bundle Move at Different Speeds
195
7.9.2.2
The Mean Length of Spindle MTs is
40%
of the Total Spindle
Length
195
7.9.3
Hierarchical Transmission of F-Actin Motion Through Focal
Adhesions
199
7.10
Outlook: Speckle Fluctuation Analysis to Probe Material
Properties
200
7.11
Conclusions
202
References
203
8
Harnessing Biological Motors to Engineer Systems for Nanoscale
Transport and Assembly
207
Anita Goel and Viola
Vogel
8.1
Sequential Assembly and Polymerization
207
8.1.1
Engineering Principle No.
1:
discrimination of similar building
blocks
209
8.2
Cargo Transport
210
8.2.1
Engineering Principle No.
2:
various track designs
212
8.3
Cargo Selection
215
8.3.1
Engineering Principle No.
3:
barcoding
215
8.3.2
Engineering Principle No.
4:
active transport of tailored drugs and
gene carriers
218
8.4
Quality Control
218
8.4.1
Engineering Principle No.
5:
error recognition and repair at the
molecular level
219
8.4.2
Engineering Principle No.
6:
error recognition and repair at the
system level
220
8.5
External Control
220
Contents
8.5.1 Engineering
Principle No.
7:
performance regulation on demand
220
8.6
Concluding Remarks
223
References
225
Part Four Innovative Disease Treatments and Regenerative Medicine
233
9
Mechanical Forces Matter in Health and Disease:
From Cancer to Tissue Engineering
235
Viola
Vogel
and Michael P. Sheetz
9.1
Introduction: Mechanical Forces and Medical Indications
235
9.2
Force-Bearing Protein Networks Hold the Tissue Together
237
9.2.1
Cell-Cell Junctions
237
9.2.2
Cell-Matrix Junctions
238
9.3
Nanotechnology has Opened a new Era in Protein Research
241
9.3.1
Mechanochemical Signal Conversion and
Mechanotransduction
241
9.3.2
Mechanical Forces and Structure-Function Relationships
242
9.4
Making the Very First Contacts
244
9.4.1
Molecular Players of Cell-Extracellular Matrix Junctions
244
9.4.1.1
Fibronectin
245
9.4.1.2
Integrins
246
9.4.1.3
Talin
247
9.4.1.4
Other Scaffolding Proteins that Provide a Linkage Between
Integrins
and F-Actin
250
9.4.1.5
Cell Cytoskeleton
250
9.5
Force-Upregulated Maturation of Early Cell-Matrix Adhesions
250
9.5.1
Protein Stretching Plays a Central Role
250
9.5.1.1
Vinculin is Recruited to Stretched Talin in a Force-dependent
Manner
251
9.6
Cell Signaling by Force-Upregulated Phosphorylation of Stretched
Proteins
252
9.6.1
Phosphorylation is Central to Regulating Cell Phenotypes
252
9.6.1.1
Stretch-Dependent Binding of Some Cytoplasmic Proteins to
Cytoskeletons
254
9.6.1.2
Tyrosine Phosphorylation as a General Mechanism of Force
Sensing
255
9.7
Dynamic Interplay between the Assembly and Disassembly of
Adhesion Sites
257
9.7.1
Molecular Players of the Adhesome
257
9.8
Forces that Cells Apply to Mature Cell-Matrix and Cell-Cell
Junctions
261
9.8.1
Insights Obtained from Micro- and Nanofabricated Tools
26Í
9.9
Sensing Matrix Rigidity
263
9.9.1
Reciprocity of the Physical Aspects of the Extracellular Matrix
and Intracellular Events
263
Contents
XI
9.9.1.1
Time Dependence and Rigidity Responses
266
9.9.1.2
Position and Spacing Dependence of the Rigidity Responses
267
9.10
Cellular Response to Initial Matrix Conditions
269
9.10.1
Assembly, Stretching and Remodeling of the Extracellular
Matrix
269
9.10.1.1
Switching the Biochemistry Displayed by the Matrix by Stretching
and Unfolding of Matrix Proteins
270
9.10.1.2
Cell Responses to Initial
Biomaterial
Properties and Later to
Self-Made Extracellular Matrix
273
9.11
Cell Motility in Response to Force Generation and Matrix
Properties
275
9.12
Mechanical Forces and Force Sensing in Development and
Disease
276
9.12.1
Cancer and Cell Transformation
277
9.12.2
Angiogenesis
279
9.12.3
Tissue Engineering
280
References
284
10
Stem Cells and Nanomedicine: Nanomechanics of the
Microenvironment 305
Florian
Rehfeldt, Adam
J.
Engler,
and Dennis E. Discher
10.1
Introduction
305
10.2
Stem Cells in
Microenvironment 305
10.2.1
Adult Stem Cells
305
10.2.2
Probing the Nanoelasticity of Cell
Microenvironments 308
10.2.3
Physical Properties of Ex-Vivo
Microenvironments 311
10.3
In Vitro
Microenvironments 312
10.3.1
Cells Probe and Feel their Mechanical
Microenvironment 313
10.3.2
Cells React to External Forces
315
10.3.3
Adult Stem Cell Differentiation
316
10.3.4
Implications for Regenerative Medicine
318
10.4
Future Perspectives
329
References
320
11
The Micro- and Nanoscale Architecture of the Immunological
Synapse
323
lain E. Dunlop, Michael
L
Dustin,
and Joachim P.
Spatz
11.1
Introduction
323
11.2
The Immunological Synapse
325
11.2.1
Large-Scale Structure and Supramolecular Activation Clusters
(SMACs)
325
11.2.2
TCR-p-MHC Microclusters as Important Signaling Centers
329
11.3
The Smallest Activating Units? p-MHC
Oligomers
331
11.4
Molecular-Scale Nanolithography
334
11.4.1
Block Copolymer Micellar Nanolithography
334
XII Contents
11.4.2
Micronanopatterning by Combining Block Copolymer Micellar
Nanolithography and Electron-Beam lithography
337
11.5
Therapeutic Possibilities of Immune Synapse Micro- and
Nanolithography
338
11.6
Conclusions
340
References
341
12
Bone Nanostructure and its Relevance for Mechanical Performance,
Disease and Treatment
345
Peter Fratzl, Himadri S.
Capta,
Paul Roschger, and Klaus Klaushofer
12.1
Introduction
345
12.2
Nanoscale Structure of Bone
346
12.3
Mechanical Behavior of Bone at the Nanoscale
347
12.4
Bone Mineral Density Distribution in Osteoporosis and
Treatments
349
12.4.1
Osteoporosis
351
12.5
Examples of Disorders Affecting the Structure of Bone Material
352
12.5.1
Osteogenesis
Imperfecta
352
12.5.2
Pycnodysostosis
353
12.5.3
Fluorosis
354
12.6
Conclusions
355
References
357
"1
3
Nanoengineered Systems for Tissue Engineering and Regeneration
361
AH Khademhosseini, Bimal Rajalingam, Satoshijinno, and Robert
Langer
13.1
Introduction
361
13.2
Nanomaterials Synthesized Using Top-Down Approaches
362
13.2.1
Electrospinning Nanofibers
363
13.2.2
Scaffolds with Nanogrooved Surfaces
365
13.3
Nanomaterials Synthesized using Bottom-Up Approaches
367
13.3.1
Self-Assembled
Peptide
Scaffolds
367
13.3.2
Layer-by-Layer Deposition of Nanomaterials
367
13.3.3
Carbon Nanotubes
370
13.3.4
MRI
Contrast Agents
371
13.3.5
Quantum Dots
373
13.4
Future Directions
374
13.5
Conclusions
376
References
376
14
Self-Assembling Peptide-Based Nanostructures for Regenerative
Medicine
385
Ramille M.
Capito,
Alvaro Mata,
and Samuel I. Stupp
14.1
Introduction
385
14.2
Self-Assembling Synthetic
Peptide
Scaffolds
387
14.2.1 ß-Sheet Peptides 387
Contents XJII
14.2.2 ß-Hairpin Peptides 389
14.2.3 Block Copolypeptides 391
14.2.4
Ionic Self-Complementary
Peptides 392
14.2.5 Fmoc Peptides 393
14.2.6
Peptide Amphiphiles
394
14.3
Self-Assembling
Systems
for Surface Modification
401
14.3.1
Coatings on Surfaces
401
14.3.2
Coatings on
3-D
Scaffolds
406
ХАЛ
Clinical Potential of Self-Assembling Systems
407
14.5
Conclusions
408
References
409
Index
413 |
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| illustrated | Illustrated |
| index_date | 2024-07-02T20:22:39Z |
| indexdate | 2024-07-09T21:13:48Z |
| institution | BVB |
| isbn | 9783527317363 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-016423001 |
| oclc_num | 635250115 |
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| spelling | Nanotechnology 5 Nanomedicine G. Schmid ... (eds.) Weinheim Wiley-VCH 2009 XX, 425 S. Ill., graph. Darst. 25 cm txt rdacontent n rdamedia nc rdacarrier Medizin (DE-588)4038243-6 gnd rswk-swf Nanotechnologie (DE-588)4327470-5 gnd rswk-swf Nanotechnologie (DE-588)4327470-5 s Medizin (DE-588)4038243-6 s DE-604 Vogel, Viola Sonstige oth Schmid, Günter 1937- Sonstige (DE-588)13573097X oth (DE-604)BV023237305 5 Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016423001&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Nanotechnology Medizin (DE-588)4038243-6 gnd Nanotechnologie (DE-588)4327470-5 gnd |
| subject_GND | (DE-588)4038243-6 (DE-588)4327470-5 |
| title | Nanotechnology |
| title_auth | Nanotechnology |
| title_exact_search | Nanotechnology |
| title_exact_search_txtP | Nanotechnology |
| title_full | Nanotechnology 5 Nanomedicine G. Schmid ... (eds.) |
| title_fullStr | Nanotechnology 5 Nanomedicine G. Schmid ... (eds.) |
| title_full_unstemmed | Nanotechnology 5 Nanomedicine G. Schmid ... (eds.) |
| title_short | Nanotechnology |
| title_sort | nanotechnology nanomedicine |
| topic | Medizin (DE-588)4038243-6 gnd Nanotechnologie (DE-588)4327470-5 gnd |
| topic_facet | Medizin Nanotechnologie |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016423001&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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