About the Editors xiii
List of Contributors xv
Foreword xix
Series Preface xxi
Preface xxiii
Part One BIOLOGICAL PHENOMENA
1 Cell-Receptor Interactions 3
David Lepzelter and Muhammad Zaman
1.1 Introduction 3
1.2 Mechanics of Integrins 4
1.3 Two-Dimensional Adhesion 7
1.4 Two-Dimensional Motility 9
1.5 Three-Dimensional Adhesion 11
1.6 Three-Dimensional Motility 12
1.7 Apoptosis and Survival Signaling 13
1.8 Cell Differentiation Signaling 13
1.9 Conclusions 14
References 15
2 Regulatory Mechanisms of Kinesin and Myosin Motor Proteins: Inspiration for Improved Control of Nanomachines 19
Sarah Rice
2.1 Introduction 19
2.2 Generalized Mechanism of Cytoskeletal Motors 19
2.3 Switch I: A Controller of Motor Protein and G Protein Activation 21
2.4 Calcium-Binding Regulators of Myosins and Kinesins 23
2.5 Phospho-Regulation of Kinesin and Myosin Motors 262.6 Cooperative Action of Kinesin and Myosin Motors as a "Regulator" 28
2.7 Conclusion 29
References 30
3 Neuromechanics: The Role of Tension in Neuronal Growth and Memory 35
Wylie W. Ahmed, Jagannathan Rajagopalan, Alireza Tofangchi, and Taher A. Saif
3.1 Introduction 35
3.1.1 What is a Neuron? 36
3.1.2 How Does a Neuron Function? 38
3.1.3 How Does a Neuron Grow? 40
3.2 Tension in Neuronal Growth 41
3.2.1 In Vitro Measurements of Tension in Neurons 41
3.2.2 In Vivo Measurements of Tension in Neurons 43
3.2.3 Role of Tension in Structural Development 45
3.3 Tension in Neuron Function 48
3.3.1 Tension Increases Neurotransmission 48
3.3.2 Tension Affects Vesicle Dynamics 48
3.4 Modeling the Mechanical Behavior of Axons 52
3.5 Outlook 58
References 58
Part Two NANOSCALE PHENOMENA
4 Fundamentals of Roughness-Induced Superhydrophobicity 65
Neelesh A. Patankar
4.1 Background and Motivation 65
4.2 Thermodynamic Analysis: Classical Problem (Hydrophobic to Superhydrophobic) 67
4.2.1 Problem Formulation 68
4.2.2 The Cassie-Baxter State 71
4.2.3 Predicting Transition from Cassie-Baxter to Wenzel State 73
4.2.4 The Apparent Contact Angle of the Drop 77
4.2.5 Modeling Hysteresis 79
4.3 Thermodynamic Analysis: Classical Problem (Hydrophilic to Superhydrophobic) 84
4.4 Thermodynamic Analysis: Vapor Stabilization 86
4.5 Applications and Future Challenges 90
Acknowledgments 91
References 91
5 Multiscale Experimental Mechanics of Hierarchical Carbon-Based Materials 95
Horacio D. Espinosa, Tobin Filleter, and Mohammad Naraghi
5.1 Introduction 95
5.2 Multiscale Experimental Tools 97
5.2.1 Revealing Atomic-Level Mechanics: In-Situ TEM Methods 98
5.2.2 Measuring Ultralow Forces: AFM Methods 101
5.2.3 Investigating Shear Interactions: In-Situ SEM/AFM Methods 102
5.2.4 Collective and Local Behavior: Micromechanical Testing Methods 103
5.3 Hierarchical Carbon-Based Materials 106
5.3.1 Weak Shear Interactions between Adjacent Graphitic Layers 106
5.3.2 Cross-linking Adjacent Graphitic Layers 110
5.3.3 Local Mechanical Properties of CNT/Graphene Composites 113
5.3.4 High Volume Fraction CNT Fibers and Composites 115
5.4 Concluding Remarks 120
References 123
6 Mechanics of Nanotwinned Hierarchical Metals 129
Xiaoyan Li and Huajian Gao
6.1 Introduction and Overview 129
6.1.1 Nanotwinned Materials 130
6.1.2 Numerical Modeling of Nanotwinned Metals 132
6.2 Microstructural Characterization and Mechanical Properties of Nanotwinned Materials 134
6.2.1 Structure of Coherent Twin Boundary 134
6.2.2 Microstructures of Nanotwinned Materials 135
6.2.3 Mechanical and Physical Properties of Nanotwinned Metals 137
6.3 Deformation Mechanisms in Nanotwinned Metals 145
6.3.1 Interaction between Dislocations and Twin Boundaries 146
6.3.2 Strengthening and Softening Mechanisms in Nanotwinned Metals 147
6.3.3 Fracture of Nanotwinned Copper 155
6.4 Concluding Remarks 156
References 157
7 Size-Dependent Strength in Single-Crystalline Metallic Nanostructures 163
Julia R. Greer
7.1 Introduction 163
7.2 Background 164
7.2.1 Experimental Foundation 164
7.2.2 Models 167
7.3 Sample Fabrication 170
7.3.1 FIB Approach 170
7.3.2 Directional Solidification and Etching 172
7.3.3 Templated Electroplating 173
7.3.4 Nanoimprinting 173
7.3.5 Vapor-Liquid-Solid Growth 174
7.3.6 Nanowire Growth 175
7.4 Uniaxial Deformation Experiments 175
7.4.1 Nanoindenter-Based Systems (Ex Situ) 176
7.4.2 In-Situ Systems 176
7.5 Discussion and Outlook on Size-Dependent Strength in Single-Crystalline Metals 178
7.5.1 Cubic Crystals 178
7.5.2 Non-Cubic Single Crystals 183
7.6 Conclusions and Outlook 184
References 185
Part Three EXPERIMENTATION
8 In-Situ TEM Electromechanical Testing of Nanowires and Nanotubes 193
Horacio D. Espinosa, Rodrigo A. Bernal, and Tobin Filleter
8.1 Introduction 193
8.1.1 Relevance of Mechanical and Electromechanical Testing for One-Dimensional Nanostructures 194
8.1.2 Mechanical and Electromechanical Characterization of Nanostructures: The Need for In-Situ TEM 196
8.2 In-Situ TEM Experimental Methods 197
8.2.1 Overview of TEM Specimen Holders 199
8.2.2 Methods for Mechanical and Electromechanical Testing of Nanowires and Nanotubes 200
8.2.3 Sample Preparation for TEM of One-Dimensional Nanostructures 208
8.3 Capabilities of In-Situ TEM Applied to One-Dimensional Nanostructures 212
8.3.1 HRTEM 212
8.3.2 Diffraction 216
8.3.3 Analytical Techniques 217
8.3.4 In-Situ Specimen Modification 218
8.4 Summary and Outlook 220
Acknowledgments 221
References 221
9 Engineering Nano-Probes for Live-Cell Imaging of Gene Expression 227
Gang Bao, Brian Wile, and Andrew Tsourkas
9.1 Introduction 227
9.2 Molecular Probes for RNA Detection 229
9.2.1 Fluorescent Linear Probes 229
9.2.2 Linear FRET Probes 232
9.2.3 Quenched Auto-ligation Probes 233
9.2.4 Molecular Beacons 234
9.2.5 Dual-FRET Molecular Beacons 236
9.2.6 Fluorescent Protein-Based Probes 237
9.3 Probe Design, Imaging, and Biological Issues 239
9.3.1 Specificity of Molecular Beacons 239
9.3.2 Fluorophores, Quenchers, and Signal-to-Background 241
9.3.3 Target Accessibility 242
9.4 Delivery of Molecular Beacons 244
9.4.1 Microinjection 245
9.4.2 Cationic Transfection Agents 245
9.4.3 Electroporation 245
9.4.4 Chemical Permeabilization 246
9.4.5 Cell-Penetrating Peptide 246
9.5 Engineering Challenges and Future Directions 248
Acknowledgments 249
References 249
10 Towards High-Throughput Cell Mechanics Assays for Research and Clinical Applications 255
David R. Myers, Daniel A. Fletcher, and Wilbur A. Lam
10.1 Cell Mechanics Overview 255
10.1.1 Cell Cytoskeleton and Cell-Sensing Overview 256
10.1.2 Forces Applied by Cells 259
10.1.3 Cell Responses to Force and Environment 260
10.1.4 General Principles of Combined Mechanical and Biological Measurements 261
10.2 Bulk Assays 262
10.2.1 Microfiltration 262
10.2.2 Rheometry 264
10.2.3 Ektacytometry 266
10.2.4 Parallel-Plate Flow Chambers 267
10.3 Single-Cell Techniques 268
10.3.1 Micropipette Aspiration 268
10.3.2 Atomic Force Microscopy 270
10.3.3 Microplate Stretcher 272
10.3.4 Optical Tweezers 273
10.4 Existing High-Throughput Cell Mechanical-Based Assays 274
10.4.1 Optical Stretchers 274
10.4.2 Traction Force Microscopy via Bead-Embedded Gels 275
10.4.3 Traction Force Microscopy via Micropost Arrays 275
10.4.4 Substrate Stretching Assays 277
10.4.5 Magnetic Twisting Cytometry 277
10.4.6 Microfluidic Pore and Deformation Assays 278
10.5 Cell Mechanical Properties and Diseases 280
References 284
11 Microfabricated Technologies for Cell Mechanics Studies 293
Sri Ram K. Vedula, Man C. Leong, and Chwee T. Lim
11.1 Introduction 293
11.2 Microfabrication Techniques 294
11.2.1 Photolithography and Soft Lithography 294
11.2.2 Microphotopatterning (¿PP) 297
11.3 Applications to Cell Mechanics 298
11.3.1 Micropatterned Substrates 298
11.3.2 Micropillared Substrates 301
11.3.3 Microfluidic Devices 304
11.4 Conclusions 307
References 307
Part Four MODELING
12 Atomistic Reaction Pathway Sampling: The Nudged Elastic BandMethod and Nanomechanics Applications 313
Ting Zhu, Ju Li, and Sidney Yip
12.1 Introduction 313
12.1.1 Reaction Pathway Sampling in Nanomechanics 314
12.1.2 Extending the Time Scale in Atomistic Simulation 314
12.1.3 Transition-State Theory 315
12.2 The NEB Method for Stress-Driven Problems 315
12.2.1 The NEB method 315
12.2.2 The Free-End NEB Method 317
12.2.3 Stress-Dependent Activation Energy and Activation Volume 320
12.2.4 Activation Entropy and Meyer-Neldel Compensation Rule 322
12.3 Nanomechanics Case Studies 324
12.3.1 Crack Tip Dislocation Emission 324
12.3.2 Stress-Mediated Chemical Reactions 326
12.3.3 Bridging Modeling with Experiment 327
12.3.4 Temperature and Strain-Rate Dependence of Dislocation Nucleation 329
12.3.5 Size and Loading Effects on Fracture 330
12.4 A Perspective on Microstructure Evolution at Long Times 332
12.4.1 Sampling TSP Trajectories 333
12.4.2 Nanomechanics in Problems of Materials Ageing 334
References 336
13 Mechanics of Curvilinear Electronics 339
Shuodao Wang, Jianliang Xiao, Jizhou Song, Yonggang Huang, and John A. Rogers
13.1 Introduction 339
13.2 Deformation of Elastomeric Transfer Elements during Wrapping Processes 342
13.2.1 Strain Distribution in Stretched Elastomeric Transfer Elements 342
13.2.2 Deformed Shape of Elastomeric Transfer Elements 344
13.3 Buckling of Interconnect Bridges 347
13.4 Maximum Strain in the Circuit Mesh 351
13.5 Concluding Remarks 355
Acknowledgments 355
References 355
14 Single-Molecule Pulling: Phenomenology and Interpretation 359
Ignacio Franco, Mark A. Ratner, and George C. Schatz
14.1 Introduction 359
14.2 Force-Extension Behavior of Single Molecules 360
14.3 Single-Molecule Thermodynamics 364
14.3.1 Free Energy Profile of the Molecule Plus Cantilever 365
14.3.2 Extracting the Molecular Potential of Mean Force ¿(¿ ) 366
14.3.3 Estimating Force-Extension Behavior from ¿(¿ ) 369
14.4 Modeling Single-Molecule Pulling Using Molecular Dynamics 370
14.4.1 Basic Computational Setup 370
14.4.2 Modeling Strategies 371
14.4.3 Examples 373
14.5 Interpretation of Pulling Phenomenology 376
14.5.1 Basic Structure of the Molecular Potential of Mean Force 377
14.5.2 Mechanical Instability 378
14.5.3 Dynamical Bistability 381
14.6 Summary 384
Acknowledgments 385
References 385
15 Modeling and Simulation of Hierarchical Protein Materials 389
Tristan Giesa, Graham Bratzel, and Markus J. Buehler
15.1 Introduction 389
15.2 Computational and Theoretical Tools 391
15.2.1 Molecular Simulation from Chemistry Upwards 391
15.2.2 Mesoscale Methods for Modeling Larger Length and Time Scales 392
15.2.3 Mathematical Approaches to Biomateriomics 394
15.3 Case Studies 400
15.3.1 Atomistic and Mesoscale Protein Folding and Deformation in Spider Silk 400
15.3.2 Coarse-Grained Modeling of Actin Filaments 402
15.3.3 Category Theoretical Abstraction of a Protein Material and Analogy to an Office Network 403
15.4 Discussion and Conclusion 406
Acknowledgments 406
References 406
16 Geometric Models of Protein Secondary-Structure Formation 411
Hendrik Hansen-Goos and Seth Lichter
16.1 Introduction 411
16.2 Hydrophobic Effect 412
16.2.1 Variable Hydrogen-Bond Strength 415
16.3 Prior Numerical and Coarse-Grained Models 415
16.4 Geometry-Based Modeling: The Tube Model 416
16.4.1 Motivation 416
16.4.2 Impenetrable Tube Models 417
16.4.3 Including Finite-Sized Particles Surrounding the Protein 419
16.4.4 Models Using Real Protein Structure 421
16.5 Morphometric Approach to Solvation Effects 422
16.5.1 Hadwiger's Theorem 422
16.5.2 Applications 424
16.6 Discussion, Conclusions, Future Work 429
16.6.1 Results 429
16.6.2 Discussion and Speculations 430
Acknowledgments 433
References 433
17 Multiscale Modeling for the Vascular Transport of Nanoparticles 437
Shaolie S. Hossain, Adrian M. Kopacz, Yongjie Zhang, Sei-Young Lee, Tae-Rin Lee, Mauro Ferrari, Thomas J.R. Hughes, Wing Kam Liu, and Paolo Decuzzi
17.1 Introduction 437
17.2 Modeling the Dynamics of NPs in the Macrocirculation 438
17.2.1 The 3D Reconstruction of the Patient-Specific Vasculature 439
17.2.2 Modeling the Vascular Flow and Wall Adhesion of NPs 440
17.2.3 Modeling NP Transport across the Arterial Wall and Drug Release 440
17.3 Modeling the NP Dynamics in the Microcirculation 448
17.3.1 Semi-analytical Models for the NP Transport 449
17.3.2 An IFEM for NP and Cell Transport 452
17.4 Conclusions 456
Acknowledgments 456
References 457
Index 461
