Nano and Cell Mechanics
Fundamentals and Frontiers
The Wiley Microsystem and Nanotechnology Series

Research in nano and cell mechanics has received much attention from the scientific community as a result of society needs and government initiatives to accelerate developments in materials, manufacturing, electronics, medicine and healthcare, energy, and the environment. Engineers and scientists are currently engaging in increasingly complex scientific problems that require interdisciplinary approaches. In this regard, studies in this field draw from fundamentals in atomistic scale phenomena, biology, statistical and continuum mechanics, and multiscale modeling and experimentation. As a result, contributions in these areas are spread over a large number of specialized journals, which prompted the Editors to assemble this book.

Nano and Cell Mechanics: Fundamentals and Frontiers brings together many of the new developments in the field for the first time, and covers fundamentals and frontiers in mechanics to accelerate developments in nano- and bio-technologies.

Key features:

? Provides an overview of recent advances in nano and cell mechanics.

? Covers experimental, analytical, and computational tools used to investigate biological and nanoscale phenomena.

?  Covers fundamentals and frontiers in mechanics to accelerate developments in nano- and bio-technologies.

? Presents multiscale-multiphysics modeling and experimentation techniques.

? Examines applications in materials, manufacturing, electronics, medicine and healthcare.

Nano and Cell Mechanics: Fundamentals and Frontiers is written by internationally recognized experts in theoretical and applied mechanics, applied physics, chemistry, and biology. It is an invaluable reference for graduate students of nano- and bio-technologies, researchers in academia and industry who are working in nano and cell mechanics, and practitioners who are interested in learning about the latest analysis tools. The book can also serve as a text for graduate courses in theoretical and applied mechanics, mechanical engineering, materials science, and applied physics.

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 (μPP) 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 φ(ξ ) 366

14.3.3 Estimating Force–Extension Behavior from φ(ξ ) 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

Horacio D. Espinosa, Northwestern University, USA
Horacio D. Espinosa is the James and Nancy Farley Professor of Mechanical Engineering at Northwestern University, USA. He is a member of the European Academy of Arts and Sciences, and Fellow of AAM, ASME, and SEM. He served as Editor-in-chief of the Journal of Experimental Mechanics and Associate Editor of the Journal of Applied Mechanics. Currently, he is a co-editor of the Wiley Book Series in Micro and Nanotechnologies and serves in several journal editorial boards. His research interests include biomimetics, size scale electro-mechanical properties of nanomaterials, NEMS, in-situ microscopy testing of nanostructures, and the development of microdevices for tip-based nanofabrication and single cell studies.

Gang Bao, Georgia Institute of Technology, USA
Gang Bao is Professor of Bioengineering at the Georgia Institute of Technology, USA. His research interests include biomolecular engineering, bionanotechnology, molecular imaging and molecular biomechanics.