List of Contributors xiii
Preface xvii
1 Extracellular Matrix Structure and Stem Cell Mechanosensing 1
Nicholas D. Evans and Camelia G. Tusan
1.1 Mechanobiology 1
1.2 Stem Cells 3
1.3 Substrate Stiffness in Cell Behavior 5
1.3.1 A Historical Perspective on Stiffness Sensing 5
1.4 Stem Cells and Substrate Stiffness 7
1.4.1 ESCs and Substrate Stiffness 8
1.4.2 Collective Cell Behavior in Substrate Stiffness Sensing 11
1.5 Material Structure and Future Perspectives in Stem Cell Mechanobiology 14
1.6 Conclusion 15
References 16
2 Molecular Pathways of Mechanotransduction: From Extracellular Matrix to Nucleus 23
Hamish T. J. Gilbert and Joe Swift
2.1 Introduction: Mechanically Influenced Cellular Behavior 23
2.2 Mechanosensitive Molecular Mechanisms 24
2.3 Methods Enabling the Study of Mechanobiology 29
2.4 Conclusion 34
Acknowledgements 34
References 34
3 Sugar?-Coating the Cell: The Role of the Glycocalyx in Mechanobiology 43
Stefania Marcotti and Gwendolen C. Reilly
3.1 What is the Glycocalyx? 43
3.2 Composition of the Glycocalyx 44
3.3 Morphology of the Glycocalyx 45
3.4 Mechanical Properties of the Glycocalyx 46
3.5 Mechanobiology of the Endothelial Glycocalyx 49
3.6 Does the Glycocalyx Play a Mechanobiological Role in Bone? 50
3.7 Glycocalyx in Muscle 52
3.8 How Can the Glycocalyx be Exploited for Medical Benefit? 53
3.9 Conclusion 53
References 54
4 The Role of the Primary Cilium in Cellular Mechanotransduction: An Emerging Therapeutic Target 61
Kian F. Eichholz and David A. Hoey
4.1 Introduction 61
4.2 The Primary Cilium 63
4.3 Cilia?-Targeted Therapeutic Strategies 68
4.4 Conclusion 70
Acknowledgements 70
References 70
5 Mechanosensory and Chemosensory Primary Cilia in Ciliopathy and Ciliotherapy 75
Surya M. Nauli, Rinzhin T. Sherpa, Caretta J. Reese, and Andromeda M. Nauli
5.1 Introduction 75
5.2 Mechanobiology and Diseases 76
5.3 Primary Cilia as Biomechanics 78
5.4 Modulating Mechanobiology Pathways 83
5.5 Conclusion 85
References 86
6 Mechanobiology of Embryonic Skeletal Development: Lessons for Osteoarthritis 101
Andrea S. Pollard and Andrew A. Pitsillides
6.1 Introduction 101
6.2 An Overview of Embryonic Skeletal Development 102
6.3 Regulation of Joint Formation 103
6.4 Regulation of Endochondral Ossification 105
6.5 An Overview of Relevant Osteoarthritic Joint Changes 106
6.6 Lessons for Osteoarthritis from Joint Formation 108
6.7 Lessons for Osteoarthritis from Endochondral Ossification 109
6.8 Conclusion 110
Acknowledgements 111
References 111
7 Modulating Skeletal Responses to Mechanical Loading by Targeting Estrogen Receptor Signaling 115
Gabriel L. Galea and Lee B. Meakin
7.1 Introduction 115
7.2 Biomechanical Activation of Estrogen Receptor Signaling: In Vitro Studies 116
7.3 Skeletal Consequences of Altered Estrogen Receptor Signaling: In Vivo Mouse Studies 120
7.4 Skeletal Consequences of Human Estrogen Receptor Polymorphisms: Human Genetic and Exercise?-Intervention Studies 125
7.5 Conclusion 126
References 126
8 Mechanical Responsiveness of Distinct Skeletal Elements: Possible Exploitation of Low Weight?-Bearing Bone 131
Simon C. F. Rawlinson
8.1 Introduction 131
8.2 Anatomy and Loading?-Related Stimuli 132
8.3 Preosteogenic Responses In Vitro 135
8.4 Site?-Specific, Animal?-Strain Differences 136
8.5 Exploitation of Regional Information 137
8.6 Conclusion 138
References 138
9 Pulmonary Vascular Mechanics in Pulmonary Hypertension 143
Zhijie Wang, Lian Tian, and Naomi C. Chesler
9.1 Introduction 143
9.2 Pulmonary Vascular Mechanics 143
9.3 Measurements of Pulmonary Arterial Mechanics 147
9.4 Mechanobiology in Pulmonary Hypertension 150
9.5 Computational Modeling in Pulmonary Circulation 151
9.6 Impact of Pulmonary Arterial Biomechanics on the Right Heart 152
9.7 Conclusion 153
References 153
10 Mechanobiology and the Kidney Glomerulus 161
Franziska Lausecker, Christoph Ballestrem, and Rachel Lennon
10.1 Introduction 161
10.2 Glomerular Filtration Barrier 161
10.3 Podocyte Adhesion 163
10.4 Glomerular Disease 165
10.5 Forces in the Glomerulus 166
10.6 Mechanosensitive Components and Prospects for Therapy 167
10.7 Conclusion 169
References 169
11 Dynamic Remodeling of the Heart and Blood Vessels: Implications of Health and Disease 175
Ken Takahashi, Hulin Piao, and Keiji Naruse
11.1 Introduction 175
11.2 Causes of Remodeling 176
11.3 Mechanical Transduction in Cardiac Remodeling 177
11.4 The Remodeling Process 178
11.5 Conclusion 183
References 183
12 Aortic Valve Mechanobiology: From Organ to Cells 191
K. Jane Grande?-Allen, Daniel Puperi, Prashanth Ravishankar, and Kartik Balachandran
12.1 Introduction 191
12.2 Mechanobiology at the Organ Level 192
12.3 Mechanobiology at the Cellular Level 197
12.4 Conclusion 201
Acknowledgments 201
References 201
13 Testing the Perimenopause Ageprint using Skin Visoelasticity under Progressive Suction 207
Gérald E. Piérard, Claudine Piérard?-Franchimont, Ulysse Gaspard, Philippe Humbert, and Sébastien L. Piérard
13.1 Introduction 207
13.2 Gender?-Linked Skin Aging 208
13.3 Dermal Aging, Thinning, and Wrinkling 209
13.4 Skin Viscoelasticity under Progressive Suction 209
13.5 Skin Tensile Strength during the Perimenopause 211
13.6 Conclusion 214
Acknowledgements 215
References 216
14 Mechanobiology and Mechanotherapy for Skin Disorders 221
Chao?-Kai Hsu and Rei Ogawa
14.1 Introduction 221
14.2 Skin Disorders Associated with Mechanobiological Dysfunction 223
14.3 Mechanotherapy 231
14.4 Conclusion 232
Acknowledgement 232
References 233
15 Mechanobiology and Mechanotherapy for Cutaneous Wound?-Healing 239
Chenyu Huang, Yanan Du, and Rei Ogawa
15.1 Introduction 239
15.2 The Mechanobiology of Cutaneous Wound?-Healing 240
15.3 Mechanotherapy to Improve Cutaneous Wound?-Healing 242
15.4 Future Considerations 246
References 246
16 Mechanobiology and Mechanotherapy for Cutaneous Scarring 255
Rei Ogawa and Chenyu Huang
16.1 Introduction 255
16.2 Cutaneous Wound?-Healing and Mechanobiology 255
16.3 Cutaneous Scarring and Mechanobiology 256
16.4 Cellular and Tissue Responses to Mechanical Forces 257
16.5 Keloids and Hypertrophic Scars and Mechanobiology 258
16.6 Relationship Between Scar Growth and Tension 260
16.7 A Hypertrophic Scar Animal Model Based on Mechanotransduction 261
16.8 Mechanotherapy for Scar Prevention and Treatment 262
16.9 Conclusion 263
References 264
17 Mechanobiology and Mechanotherapy for the Nail 267
Hitomi Sano and Rei Ogawa
17.1 Introduction 267
17.2 Nail Anatomy 267
17.3 Role of Mechanobiology in Nail Morphology 268
17.4 Nail Diseases and Mechanical Forces 269
17.5 Current Nail Treatment Strategies 270
17.6 Mechanotherapy for Nail Deformities 270
17.7 Conclusion 271
References 271
18 Bioreactors: Recreating the Biomechanical Environment In Vitro 275
James R. Henstock and Alicia J. El Haj
18.1 The Mechanical Environment: Forces in the Body 275
18.2 Bioreactors: A Short History 276
18.3 Bioreactor Types 278
18.4 Commercial versus Homemade Bioreactors 288
18.5 Automated Cell?-Culture Systems 289
18.6 The Future of Bioreactors in Research and Translational Medicine 290
References 291
19 Cell Sensing of the Physical Properties of the Microenvironment at Multiple Scales 297
Julien E. Gautrot
19.1 Introduction 297
19.2 Cells Sense their Mechanical Microenvironment at the Nanoscale Level 298
19.3 Cell Sensing of the Nanoscale Physicochemical Landscape of the Environment 306
19.4 Cell Sensing of the Microscale Geometry and Topography of the Environment 312
19.5 Conclusion 319
References 319
20 Predictive Modeling in Musculoskeletal Mechanobiology 331
Hanifeh Khayyeri, Hanna Isaksson, and Patrick J. Prendergast
20.1 What is Mechanobiology? Background and Concepts 331
20.2 Examples of Mechanobiological Experiments 333
20.3 Modeling Mechanobiological Tissue Regeneration 337
20.4 Mechanoregulation Theories for Bone Regeneration 338
20.5 Use of Computational Modeling Techniques to Corroborate Theories and Predict Experimental Outcomes 340
20.6 Horizons of Computational Mechanobiology 341
References 343
21 Porous Bone Graft Substitutes: When Less is More 347
Charlie Campion and Karin A. Hing
21.1 Introduction 347
21.2 Bone: The Ultimate Smart Material 350
21.3 Bone?-Grafting Classifications 353
21.4 Synthetic Bone Graft Structures 356
21.5 Conclusion 361
References 362
22 Exploitation of Mechanobiology for Cardiovascular Therapy 373
Winston Elliott, Amir Keshmiri, and Wei Tan
22.1 Introduction 373
22.2 Arterial Wall Mechanics and Mechanobiology 374
22.3 Mechanical Signal and Mechanotransduction on the Arterial Wall 375
22.4 Physiological and Pathological Responses to Mechanical Signals 377
22.5 The Role of Vascular Mechanics in Modulating Mechanical Signals 378
22.6 Therapeutic Strategies Exploiting Mechanobiology 380
22.7 The Role of Hemodynamics in Mechanobiology 381
22.8 Conclusion 390
References 391
Index 401
