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	Preface	XV
	List of Contributors	XXI
I	Self-Assembly and Nanoparticles: Novel Principles	1
1	Self-Assembled Artificial Transmembrane Ion Channels Mary S. Gin, Emily G. Schmidt, and Pinaki Talukdar	3
1.1	Overview	3
1.1.1	Non-Gated Channels	3
1.1.1.1	Aggregates	4
1.1.1.2	Half-Channel Dimers	5
1.1.1.3	Monomolecular Channels	5
1.1.2	Gated Channels	6
1.1.2.1	Light-Gated Channels	7
1.1.2.2	Voltage-Gated Channels	7
1.1.2.3	Ligand-Gated Channels	9
1.2	Methods	10
1.2.1	Planar Bilayers	10
1.2.2	Vesicles	11
1.2.2.1	²³Na NMR	11
1.2.2.2	pH-Stat	11
1.2.2.3	Fluorescence	12
1.2.2.4	Ion-Selective Electrodes	12
1.3	Outlook	12
	References	12
2	Self-Assembling Nanostructures from Coiled-Coil Peptides Maxim G. Ryadnov and Derek N. Woolfson	17
2.1	Background and Overview	17
2.1.1	Introduction: Peptides in Self-Assembly	17
2.1.2	Coiled-Coil Peptides as Building Blocks in Supramolecular Design	18
2.1.3	Coiled-Coil Design in General	20
2.2	Methods and Examples	20
2.2.1	Ternary Coiled-Coil Assemblies and Nanoscale-Linker Systems	20
2.2.2	Fibers Assembled Using Linear Peptides	22
2.2.3	Fibers Assembled Using Protein Fragments and Nonlinear Peptide Building Blocks	26
2.2.4	Summary: Pros and Cons of Peptide-Based Assembly of Nanofibers	27
2.2.5	Assembling More-Complex Matrices Using Peptide Assemblies as Linker Struts	30
2.2.5.1	Programmed Matrices Assembled Exclusively from Coiled-Coil Building Blocks	30
2.2.5.2	Synthetic Polymer-Coiled-Coil Hybrids	31
2.2.6	Key Techniques	33
2.3	Conclusions and Perspectives	34
	References	35
3	Synthesis and Assembly of Nanoparticles and Nanostructures Using Bio-Derived Templates Erik Dujardin and Stephen Mann	39
3.1	Introduction: Elegant Complexity	39
3.2	Polysaccharides, Synthetic Peptides, and DNA	40
3.3	Proteins	44
3.4	Viruses	48
3.5	Microorganisms	54
3.6	Outlook	56
	Acknowledgments	58
	References	58
4	Proteins and Nanoparticles: Covalent and Noncovalent Conjugates Rochelle R. Arvizo, Mrinmoy De, and Vincent M. Rotello	65
4.1	Overview	65
4.1.1	Covalent Protein-Nanoparticle Conjugates	66
4.1.2	Noncovalent Protein--NP Conjugation	69
4.2	Methods	72
4.2.1	General Methods for Noncovalent Protein--NP Conjugation	72
4.2.2	General Methods for Covalent Protein--NP Conjugation	74
4.3	Outlook	75
	References	75
5	Self-Assembling DNA Nanostructures for Patterned Molecular Assembly Thomas H. LaBean, Kurt V. Gothelf, and John H. Reif	79
	Abstract	79
5.1	Introduction	79
5.2	Overview of DNA Nanostructures	80
5.3	Three-Dimensional (3-D) DNA Nanostructures	84
5.4	Programmed Patterning of DNA Nanostructures	84
5.5	DNA-Programmed Assembly of Biomolecules	87
5.6	DNA-Programmed Assembly of Materials	89
5.7	Laboratory Methods	91
5.7.1	Annealing for DNA Assembly	92
5.7.2	AFM Imaging	93
5.8	Conclusions	93
	Acknowledgments	94
	References	94
6	Biocatalytic Growth of Nanoparticles for Sensors and Circuitry Ronan Baron, Bilha Willner, and Itamar Willner	99
6.1	Overview	99
6.1.1	Enzyme-Stimulated Synthesis of Metal Nanoparticles	100
6.1.2	Enzyme-Stimulated Synthesis of Cupric Ferrocyanide Nanoparticles	107
6.1.3	Cofactor-Induced Synthesis of Metallic NPs	107
6.1.4	Enzyme--Metal NP Hybrid Systems as ``Inks'' for the Synthesis of Metallic Nanowires	113
6.2	Methods	115
6.2.1	Physical Tools to Characterize the Growth of Nanoparticles and Nanowires	115
6.2.2	General Procedure for Monitoring the Biocatalytic Enlargement of Metal NPs in Solutions	116
6.2.3	Modification of Surfaces with Metal NPs and their Biocatalytic Growth for Sensing	116
6.2.4	Modification of Enzymes with NPs and their Use as Biocatalytic Templates for Metallic Nanocircuitry	117
6.3	Outlook	117
	References	118
II	Nanostructures for Analytics	123
7	Nanoparticles for Electrochemical Bioassays Joseph Wang	125
7.1	Overview	125
7.1.1	Particle-Based Bioassays	125
7.1.2	Electrochemical Bioaffinity Assays	125
7.1.3	NP-Based Electrochemical Bioaffinity Assays	126
7.1.3.1	Gold and Silver Metal Tags for Electrochemical Detection of DNA and Proteins	126
7.1.3.2	NP-Induced Conductivity Detection	129
7.1.3.3	Inorganic Nanocrystal Tags: Towards Electrical Coding	130
7.1.3.4	Use of Magnetic Beads	133
7.1.3.5	Ultrasensitive Particle-Based Assays Based on Multiple Amplification Schemes	134
7.2	Methods	136
7.3	Outlook	137
	Acknowledgments	138
	References	138
8	Luminescent Semiconductor Quantum Dots in Biology Thomas Pons, Aaron R. Clapp, Igor L. Medintz, and Hedi Mattoussi	141
8.1	Overview	141
8.1.1	QD Bioconjugates in Cell and Tissue Imaging	142
8.1.2	Quantum Dots in Immuno- and FRET-Based Assays	146
8.2	Methods	150
8.2.1	Synthesis, Characterization, and Capping Strategies	150
8.2.2	Water-Solubilization Strategies	151
8.2.3	Conjugation Strategies	151
8.3	Future Outlook	152
	Acknowledgments	153
	References	153
9	Nanoscale Localized Surface Plasmon Resonance Biosensors Katherine A. Willets, W. Paige Hall, Leif J. Sherry, Xiaoyu Zhang, Jing Zhao, and Richard P. Van Duyne	159
9.1	Overview	159
9.2	Methods	162
9.2.1	Nanofabrication of Materials for LSPR Spectroscopy and Sensing	162
9.2.1.1	Film Over Nanowells	163
9.2.1.2	Solution-Phase NSL-Fabricated Nanotriangles	164
9.2.1.3	Silver Nanocubes	166
9.2.2	Biosensing	167
9.3	Outlook	168
	Acknowledgments	169
	References	169
10	Cantilever Array Sensors for Bioanalysis and Diagnostics Hans Peter Lang, Martin Hegner, and Christoph Gerber	175
10.1	Overview	175
10.1.1	Cantilevers as Sensors	176
10.1.2	Measurement Principle	177
10.1.3	Cantilevers: Application Fields	179
10.2	Methods	180
10.2.1	Measurement Modes	180
10.2.2	Cantilever Functionalization	181
10.2.3	Experimental Procedure	184
10.3	Outlook	186
10.3.1	Recent Literature	186
10.3.2	Challenges	188
	Acknowledgments	189
	References	190
11	Shear-Force-Controlled Scanning Ion Conductance Microscopy Tilman E. Schäffer, Boris Anczykowski, Matthias Böcker, and Harald Fuchs	197
11.1	Overview	197
11.2	Methods	202
11.2.1	Shear-Force Detection	202
11.2.2	Ion Current Measurement	204
11.2.3	Shear-Force-Controlled Imaging	205
11.3	Outlook	207
	Acknowledgments	209
	References	209
12	Label-Free Nanowire and Nanotube Biomolecular Sensors for In-Vitro Diagnosis of Cancer and other Diseases James R. Heath	213
12.1	Overview	213
12.2	Background	213
12.3	Methods and Current State of the Art	216
12.3.1	Mechanisms of Sensing	216
12.3.2	The Role of the Sensing Environment	218
12.3.3	Nanosensor-Measured Antigen--Analyte On/Off Binding Rates	219
12.3.4	The Nanosensor/Microfluidic Environment	222
12.3.5	Nanosensor Fabrication	223
12.3.6	Biofunctionalizing NW and NT Nanosensors	226
12.4	Outlook	227
	Acknowledgments	227
	References	228
13	Bionanoarrays Rafael A. Vega, Khalid Salaita, Joseph J. Kakkassery, and Chad A. Mirkin	233
13.1	Overview	233
13.2	Methods	234
13.2.1	Atomic Force Microscope-Based Methods	234
13.2.2	Nanopipet Deposition	237
13.2.3	Beam-Based Methods	238
13.2.4	Contact Printing	240
13.2.5	Assembly-Based Patterning	241
13.3	Protein Nanoarrays	242
13.3.1	Strategies for Immobilizing Proteins on Nanopatterns	243
13.3.2	Bio-Analytical Applications	244
13.3.3	Dynamic and Motile Nanoarrays	246
13.3.4	Cell-Surface Interactions	246
13.4	DNA Nanoarrays	249
13.4.1	Strategies for Preparing DNA Nanoarrays	249
13.4.2	DNA-Based Schemes for Biodetection	250
13.4.3	Applications of Rationally Designed, Self-Assembled 2-D DNA Nanoarrays	251
13.5	Virus Nanoarrays	253
13.6	Outlook	254
	References	254
III	Nanostructures for Medicinal Applications	261
14	Biological Barriers to Nanocarrier-Mediated Delivery of Therapeutic and Imaging Agents Rudy Juliano	263
14.1	Overview: Nanocarriers for Delivery of Therapeutic and Imaging Agents	263
14.2	Basic Characteristics of the Vasculature and Mononuclear Phagocyte System	263
14.2.1	Possible Interactions of Nanocarriers Within the Bloodstream	264
14.2.2	Transendothelial Permeability in Various Tissues and Tumors	264
14.2.3	Mononuclear Cells and Particle Clearance	267
14.3	Cellular Targeting and Subcellular Delivery	268
14.3.1	Targeting, Entry, and Trafficking in Cells	268
14.3.2	Biological and Chemical Reagents for Cell-Specific Targeting	271
14.3.3	Reagents that Promote Cell Entry	272
14.4	Crafting NPs for Delivery: Lessons from Liposomes	273
14.4.1	Loading	273
14.4.2	Release Rates	273
14.4.3	Size and Charge	274
14.4.4	PEG and the Passivation of Surfaces	274
14.4.5	Decoration with Ligands	275
14.5	Biodistribution of Liposomes, Dendrimers, and NPs	276
14.6	The Toxicology of Nanocarriers	277
14.7	Summary	278
	References	278
15	Organic Nanoparticles: Adapting Emerging Techniques from the Electronics Industry for the Generation of Shape-Specific, Functionalized Carriers for Applications in Nanomedicine Larken E. Euliss, Julie A. DuPont, and Joseph M. DeSimone	285
15.1	Overview	285
15.2	Methods	288
15.2.1	Bottom-Up Approaches for the Synthesis of Organic Nanoparticles	288
15.2.2	Top-Down Approaches for the Fabrication of Polymeric Nanoparticles	291
15.2.2.1	Microfluidics	291
15.2.2.2	Photolithography	292
15.2.2.3	Imprint Lithography	294
15.2.2.4	IRINT	295
15.3	Outlook	297
	References	299
16	Poly(amidoamine) Dendrimer-Based Multifunctional Nanoparticles Thommey P. Thomas, Rameshwer Shukla, Istvan J. Majoros, Andrzej Myc, and James R. Baker, Jr.	305
16.1	Overview	305
16.1.1	PAMAM Dendrimers: Structure and Biological Properties	306
16.1.2	PAMAM Dendrimers as a Vehicle for Molecular Delivery into Cells	308
16.1.2.1	PAMAM Dendrimers as Encapsulation Complexes	308
16.1.2.2	Multifunctional Covalent PAMAM Dendrimer Conjugates	308
16.1.2.3	PAMAM Dendrimers as MRI Contrast Agents	312
16.1.2.4	Application of Multifunctional Clusters of PAMAM Dendrimer	312
16.2	Methods	313
16.2.1	Synthesis and Characterization of PAMAM Dendrimers	313
16.2.2	PAMAM Dendrimer: Determination of Physical Parameters	315
16.2.3	Quantification of Fluorescence of Targeted PAMAM Conjugates	315
16.3	Outlook	316
	References	316
17	Nanoparticle Contrast Agents for Molecular Magnetic Resonance Imaging Young-wook Jun, Jae-Hyun Lee, and Jinwoo Cheon	321
17.1	Introduction	321
17.2	NP-Assisted MRI	322
17.2.1	Magnetic NP Contrast Agents	323
17.2.1.1	Silica- or Dextran-Coated Iron Oxide Contrast Agents	325
17.2.1.2	Magnetoferritin	327
17.2.1.3	Magnetodendrimers and Magnetoliposomes	327
17.2.1.4	Non-Hydrolytically Synthesized High-Quality Iron Oxide NPs: A New Type of Contrast Agent	328
17.2.2	Iron Oxide NPs in Molecular MR Imaging	331
17.2.2.1	Infarction and Inflammation	332
17.2.2.2	Angiogenesis	333
17.2.2.3	Apoptosis	334
17.2.2.4	Gene Expression	335
17.2.2.5	Cancer Imaging	337
17.3	Outlook	340
	Acknowledgments	342
	References	342
18	Micro- and Nanoscale Control of Cellular Environment for Tissue Engineering Ali Khademhosseini, Yibo Ling, Jeffrey M. Karp, and Robert Langer	347
18.1	Overview	347
18.1.1	Cell--Substrate Interactions	347
18.1.2	Cell Shape	350
18.1.3	Cell--Cell Interactions	351
18.1.4	Cell-Soluble Factor Interactions	351
18.1.5	3-D Scaffolds	352
18.2	Methods	354
18.2.1	Soft Lithography	354
18.2.2	Self-Assembled Monolayers	356
18.2.3	Electrospinning	357
18.2.4	Nanotopography Generation	358
18.2.5	Layer-by-Layer Deposition	358
18.2.6	3D Printing	358
18.3	Outlook	359
	References	359
19	Diagnostic and Therapeutic Targeted Perfluorocarbon Nanoparticles Patrick M. Winter, Shelton D. Caruthers, Gregory M. Lanza, and Samuel A. Wickline	365
19.1	Overview	365
19.2	Methods	367
19.2.1	Diagnostic Imaging	367
19.2.2	Targeted Therapeutics	371
19.2.3	Other Imaging Modalities	373
19.3	Outlook	374
	Acknowledgments	376
	References	376
IV	Nanomotors	381
20	Biological Nanomotors Manfred Schliwa	383
20.1	Overview	383
20.2	The Architecture of the Motor Domain	388
20.3	Initial Events in Force Generation	388
20.4	Stepping, Hopping, and Slithering	390
20.5	Directionality	393
20.6	Forces	394
20.7	Motor Interactions	395
20.8	Outlook	396
	Acknowledgments	396
	References	396
21	Biologically Inspired Hybrid Nanodevices David Wendell, Eric Dy, Jordan Patti, and Carlo D. Montemagno	401
21.1	Introduction	401
21.2	An Overview	402
21.2.1	A Look in the Literature	402
21.2.2	Membrane Proteins and their Native Condition	403
21.3	The Protein Toolbox	404
21.3.1	F₀F₁-ATPase and Bacteriorhodopsin	404
21.3.2	Ion Channels and Connexin	406
21.4	Harvesting Energy	48
21.5	Methods	409
21.5.1	Muscle Power	409
21.5.2	ATPase and BR Devices	411
21.5.3	Excitable Vesicles	414
21.6	Outlook	414
	Acknowledgments	416
	References	416
	Index	419

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