Mechanosensitivity and Mechanotransduction (eBook)
XXIV, 371 Seiten
Springer Netherland (Verlag)
978-90-481-9881-8 (ISBN)
This book presents the latest findings in the field of research of mechanosensitivity and
mechanotransduction in different cells and tissues. Mechanosensitivity and mechanotransduction
of the heart and vascular cells, in the lung, in bone and joint tissues, in sensor systems and in blood cells are described in detail. This Volume focuses on molecular mechanisms of mechanosensitivity and mechanotransduction via cytoskeleton. Integrin-mediated mechanotransduction, the role of actin cytoskeleton and the role of other cytoskeletal elements are discussed. It contains a detailed description of several stretch-induced signaling cascades with multiple levels of crosstalk between different pathways. It contains a description of the role of nitric oxide in regulation of cardiac activity and in regulation of mechanically gated channels in the heart. In the heart mechanical signals are propagated into the intracellular space primarily via integrin-linked complexes, and are subsequently transmitted from cell to cell via paracrine signaling. Biochemical signals derived from mechanical stimuli activate both acute phosphorylation of signaling cascades, such as in the PI3K, FAK, and ILK pathways, and long-term morphological modii cations via intracellular cytoskeletal reorganization and
extracellular matrix remodelling. Cellular and molecular effects of mechanical stretch on vascular cells are also discussed. This Volume highlights the role of mechanotransduction in the lung, in bone and joint tissues. For the first time mechanosensitivity and mechanotransduction in blood cells are discussed. It contains new insights into mechanosensitive K+ channels functioning in mouse B lymphocytes.
This book is a unique collection of reviews outlining current knowledge and future developments
in this rapidly growing field. Currently, investigations of the molecular mechanisms of mechanosensitivity and mechanotransduction are focused on several issues. The majority of
studies investigate intracellular signaling pathways. Knowledge of the mechanisms which underlie these processes is necessary for understanding of the normal functioning of different organs and tissues and allows to predict changes, which arise due to alterations of their environment. Possibly such knowledge will allow the development of new methods of artificial intervention and therapies.
This book brings up the problem closer to the experts in related medical and biological sciences as well as practicing doctors besides just presenting the latest achievements in the field.
This book presents the latest findings in the field of research of mechanosensitivity and mechanotransduction in different cells and tissues. Mechanosensitivity and mechanotransduction are considered in the heart and vascular cells, in the lung, in bone and joint tissues, in sensor systems and in blood cells. The Volume focuses on molecular mechanisms of mechanosensitivity and mechanotransduction via cytoskeleton. Under discussion are integrin-mediated mechanotransduction, the role of actin cytoskeleton, the role of other cytoskeletal elements. It contains a detailed description of several stretch-induced signaling cascades with multiple levels of crosstalk between different pathways. Nitric oxide is discussed in regulation of cardiac activity and for the first time considered is the role of nitric oxide in regulation of mechanically gated channels in the heart. In the heart mechanical signals are propagated into the intracellular space primarily via integrin-linked complexes, and are subsequently transmitted from cell to cell via paracrine signaling. The biochemical signals derived from mechanical stimuli activate both acute phosphorylation of signaling cascades, such as in the PI3K, FAK, and ILK pathways, and long-term morphological modifications via intracellular cytoskeletal reorganization and extracellular matrix remodelling. Shown are the cellular and molecular effects of mechanical stretch on vascular cells. It highlights the role of mechanotransduction in the lung, in bone and joint tissues. For the first time mechanosensitivity and mechanotransduction in blood cells are discussed. It contains new insights into mechanosensitive K+ channels in mouse B lymphocytes. This book is a unique collection of reviews outlining current knowledge and future developments in this rapidly growing field. Currently, investigations of the molecular mechanisms of mechanosensitivity and mechanotransduction are focused on several issues. The majority of studies investigate intracellular signaling pathways. Knowledge of the mechanisms at the basis of these processes is necessary for understanding the normal functioning of different living organs and tissues and allows to predict changes, which arise due to alterations of their environment, and possibly will allow to develop new methods of artificial intervention. The book brings up the problem closer to the experts in related medical and biological sciences as well as practicing doctors besides just presenting the latest achievements in the field.
Foreword 6
Editorial 8
References 14
Contents 18
Contributors 21
Part I The Role of Cytoskeleton in Mechanosensitivity and Mechanotransduction 25
1 Integrin-Mediated Mechanotransduction in Vascular Smooth Muscle Cells 26
1.1 Introduction 26
1.2 Potential Candidates for the Sensor of Mechanotransduction 27
1.2.1 Stretch-Sensitive Ion Channels 27
1.2.2 Integrins and Their Associated Kinases 28
1.3 Integrins as Mechanotransducers in the Vascular Cells 29
1.3.1 Evidence in Endothelial Cells and Fibroblasts 30
1.3.2 Evidence in Vascular Smooth Muscle Cells 31
1.4 Mechanisms of Coupling Integrin Activation to Myogenic Constriction 31
1.4.1 Calcium-Dependent Mechanisms 31
1.4.2 Ca 2+ Independent Mechanisms 33
1.4.3 Integrins as Part of a Larger Mechanotransduction Complex 34
1.5 Integrin-Mediated Mechanotransduction in Hypertension and Vascular Remodeling 35
1.5.1 Roles of Integrins in Systemic Hypertension 35
1.5.2 Roles of Integrins in Pulmonary Hypertension 36
1.5.3 Roles of Integrins in Vascular Remodeling Caused by Mechanical Injury 37
1.6 Conclusion and Perspectives 38
References 39
2 The Role of the Actin Cytoskeleton in Mechanosensation 48
2.1 Introduction 48
2.2 Microstructures and Deformations of the Actin Cytoskeleton 50
2.2.1 Intermolecular and Intramolecular Deformations 54
2.2.1.1 Force Generation Associated with Actin Polymerization 56
2.2.1.2 Force-Dependent Behaviors of Actin-Myosin Binding 57
2.2.1.3 Force-Dependent Binding Between Actin Crosslinkers and Actin Filaments 58
2.2.1.4 Force-Dependent Intramolecular Deformation of ACLPs 59
2.2.2 Mechanical Properties of an Actin Network 60
2.2.2.1 Mechanical Properties of Pure Actin Gels 60
2.2.2.2 Effects of Crosslinking Proteins on the Microstructures and Mechanical Properties of Pure Actin Networks 62
2.2.2.3 Effects of Myosin II on the Mechanical Properties of the Actin Network 66
2.2.3 In Vivo Measurements of Cell Mechanics 67
2.3 Functions of the Actin Cytoskeleton in Mechanosensation 69
2.3.1 Mechanosensing Through Myosin II and Actin Crosslinking Proteins 69
2.3.1.1 How Force Might Modulate Myosin II Bipolar Thick Filament Assembly 72
2.3.1.2 Cooperativity Between Myosin II and Cortexillin 74
2.3.2 Mechanosensation Through Focal Adhesion Complexes 75
2.3.3 The Actin Cytoskeleton Works as a Force-Transmission Highway 76
2.4 Remodeling of the Actin Cytoskeleton During Mechanosensation 77
2.4.1 How Mechanically Activated Kinases Regulate the Actin Cytoskeleton 78
2.4.2 Crosstalk Between Microtubules and Actin Cytoskeleton 78
2.5 Experimental Techniques for Measuring Mechanosensation In Vitro and In Vivo Methods 79
2.6 Conclusion and Perspectives 80
References 81
3 Effect of Cytoskeleton on the Mechanosensitivity of Genes in Osteoblasts 89
3.1 Introduction 89
3.2 Characteristics and Roles of Cytoskeleton 90
3.2.1 Characteristics of Cytoskeleton 90
3.2.2 Roles of Cytoskeleton 90
3.2.2.1 Tensegrity Model 90
3.2.2.2 Response of Cytoskeleton to Mechanical Forces 91
3.2.2.3 Cytoskeleton and Genes' Transcription and Expression 91
3.3 Effect of Cytoskeleton on the Genes Expression in Osteoblasts 92
3.3.1 C-fos Gene 92
3.3.2 Egr-1 93
3.3.3 OPN 93
3.3.4 ERK 94
3.3.5 COX-2 94
3.4 Cytoskeleton Reorganization Inhibition Enhances the Mechanosensitivity of Some Genes in Osteoblasts 95
3.5 Conclusion and Perspectives 95
References 96
4 Involvement of the Cytoskeletal Elements in Articular Cartilage Mechanotransduction 99
4.1 Introduction 99
4.1.1 Structure and Function of the Three Major Cytoskeletal Elements 99
4.1.1.1 Actin 100
4.1.1.2 Actin-Binding Proteins 101
4.1.2 Intermediate Filaments 101
4.1.2.1 Nuclear Lamins 103
4.1.3 Tubulin Microtubules 103
4.2 Articular Cartilage Structure and Function 105
4.2.1 Tissue Composition 105
4.2.2 Tissue Function 106
4.3 Cytoskeletal Element Composition in Articular Chondrocytes 108
4.3.1 Organisation of the Cytoskeletal Elements in Articular Chondrocytes 108
4.3.2 Cytoskeletal Element Functions in Articular Chondrocytes 111
4.3.2.1 Actin Microfilaments 111
4.3.2.2 Vimentin Intermediate Filaments 111
4.3.2.3 Tubulin Microtubules 112
4.4 Biomechanics and the Chondrocyte Cytoskeleton 113
4.4.1 Contribution of the Cytoskeletal Elements to the Mechanical Properties of the Chondrocyte 113
4.4.2 Mechanical Load Influences Cytoskeletal Element Organisation 113
4.4.2.1 Actin Microfilaments 114
4.4.2.2 Vimentin Intermediate Filaments 117
4.4.2.3 Tubulin Microtubules 117
4.5 Cytoskeletal Elements in Cartilage Chondrocyte Pathology 118
4.5.1 Cytoskeletal Element Organisation in Osteoarthritic Cartilage Chondrocytes 118
4.5.2 Mechanotransduction in Osteoarthritic Cartilage: Effect(s) on the Cytoskeleton 119
4.6 Conclusions and Perspectives 120
References 121
Part II Molecular Mechanisms of Mechanotransduction and Ion Channels Modulation 129
5 The Role of Nitric Oxide in the Regulation of Mechanically Gated Channels in the Heart 130
5.1 Introduction 131
5.2 Nitric Oxide and Cardiac Function 132
5.3 The Role of Nitric Oxide in the Regulation of Mechanically Gated Channels in Isolated Ventricular Cardiomyocytes from Guinea Pig, Rat and Mouse 135
5.3.1 NO Scavenger PTIO 139
5.3.2 NO Donors 143
5.3.2.1 NO-Donor SNAP 143
5.3.2.2 NO-Donor DEA-NO 148
5.3.3 Nitric Oxide Synthases Inhibitors -- NOS Inhibits 151
5.3.4 Cardiomyocytes Derived from NOS--/--Mice 152
5.3.5 Possible Explanations of NO Involvement into Regulation of MG-Currents 152
5.4 Cell Signaling of Nitric Oxide in the Heart and Possible Role in Regulation of MG-Currents 154
5.5 Conclusion and Perspectives 156
References 156
6 Role of Signaling Pathways in the Myocardial Response to Biomechanical Stress and in Mechanotransduction in the Heart 162
6.1 Introduction 163
6.2 Cell-ECM Adhesion 164
6.2.1 Cell-ECM Adhesion: Integrin-Linked Complexes 164
6.2.1.1 Cell-ECM Adhesion: Focal Adhesion Kinase 166
6.2.1.2 Cell-ECM Adhesion: Integrin Linked Kinase 168
6.2.2 Cell-ECM Adhesion: Dystrophin-Glycoprotein Complex 170
6.3 PI3K and PTEN 171
6.3.1 PI3K 171
6.3.2 PTEN 173
6.4 Intercellular Propagation of Mechanical Signals 173
6.4.1 Cell-Cell Adhesion 173
6.4.2 Autocrine and Paracrine Signaling 175
6.5 Myocardial Remodelling 176
6.5.1 Extracellular Remodelling 176
6.5.2 Intracellular Remodelling 177
6.5.2.1 Actin 177
6.5.2.2 Zyxin 178
6.5.2.3 Gelsolin 178
6.6 Conclusion and Perspectives 179
References 179
7 Atomistic Molecular Simulation of Gating Modifier Venom Peptides -- Two Binding Modes and Effects of Lipid Structure 188
7.1 Introduction 189
7.2 Discovery and Functions of GsMTx4 189
7.3 Gating Modifier Toxins Related to GsMTx4 192
7.4 Unanswered Questions About HaTx, VsTx and GsMTx4 197
7.5 The Deep Mode Hypothesis an Insight from MD Simulations 198
7.5.1 Free Energy Analysis 199
7.5.2 Technical Consideration of Free Energy Analysis of GsMTx4/Membrane System 200
7.6 Two Binding Modes of GsMTx4/Lipid Bilayer Membrane 203
7.7 Conclusion and Perspectives 204
References 207
Part III Mechanosensitivity and Mechanotransduction in Vascular Cells 212
8 Cellular and Molecular Effects of Mechanical Stretch on Vascular Cells 213
8.1 Introduction 213
8.2 Effect of Mechanical Stress on Endothelial Cells 214
8.2.1 Effect of Shear Stress on ECs Protein Alteration 215
8.2.2 Vasculoprotective Effect of Shear Stress on ECs 215
8.2.3 Effect of Shear Stress on ECs Polarity and Morphology 217
8.2.4 Anti-Inflammatory and Anti-Oxidant Effect of Shear Stress on ECs 218
8.2.5 Effect of Disturbed Flow on ECs 220
8.2.6 Effect of Shear Stress on Endothelial Progenitor Cells 222
8.3 Effect of Mechanical Stretch on VSMC Function 223
8.3.1 Effect of Mechanical Stretch on VSMC Alignment and Differentiation 223
8.3.2 Effect of Mechanical Stretch on VSMCs Migration 224
8.3.3 Effect of Mechanical Stretch on Proliferation, Survival and Apoptosis of VSMCs 225
8.3.4 Effect of Mechanical Stretch on Vascular Remodeling 228
8.3.5 Autocrine and Paracrine Effect of Mechanical Stretch on VSMCs 229
8.4 Conclusions and Perspectives 230
References 231
9 Role of Proteoglycans in Vascular Mechanotransduction 238
9.1 Introduction 238
9.2 Proteoglycans of the Cardiovascular System 239
9.2.1 Glycosaminoglycans 239
9.2.2 Heparan Sulfate Proteoglycans 240
9.2.2.1 Perlecan 240
9.2.2.2 Glypicans 242
9.2.2.3 Syndecans 242
9.2.3 Chondroitin Sulfate/Dermatin Sulfate Proteoglycans 243
9.2.3.1 Versican 243
9.2.3.2 Biglycan 244
9.2.3.3 Decorin 244
9.2.4 Hyaluronan 244
9.2.5 Sialic Acid 244
9.2.6 Arterial Distribution of Glycoproteins 245
9.2.6.1 Glycocalyx 245
9.2.6.2 Basement Membrane 246
9.2.6.3 Arterial Wall 246
9.3 Proteoglycans in Sensing Mechanical Forces 246
9.3.1 Proteoglycans in the Control of Flow-Induced Vasodilation 246
9.3.2 Glycocalyx in Shear Stress Induced Vascular Smooth Muscle Cell Contraction 248
9.3.3 Role of HSPGs in Controlling Mechanically-Induced Changes in Cell Migration, Proliferation and Adhesion 248
9.4 Mathematical Models of Glycocalyx-Based Mechanotransduction 249
9.5 Long Term Adaptations of the Vascular System to Alterations in Mechanical Stresses 249
9.6 Conclusion and Perspectives 251
References 251
Part IV Mechanotransduction in the Lung 256
10 Control of TRPV4 and Its Effect on the Lung 257
10.1 Mechanical Stress in Lung and TRPV4 257
10.1.1 Stretch Activated Cation Channels and Lung Injury 258
10.1.2 TRPV4 is Critical for Pressure Induced Lung Injury 260
10.1.3 Phosphorylation and Mechanical Injury 262
10.1.4 Segmental Vascular Effects of TRPV4 263
10.2 TRPV4 Structure and Potential Regulatory Sites 264
10.2.1 Oligomerization and Membrane Localization 265
10.2.2 Ligand Binding Pocket 266
10.2.3 Direct Binding of EETs 266
10.2.4 Phosphorylation 267
10.2.5 Other Regulatory Domains 268
10.2.6 Homo- or Heteromultimeric Channels 268
10.3 Conclusion and Perspectives 268
References 269
11 The Role of Protein-protein Interactions in Mechanotransduction: Implications in Ventilator Induced Lung Injury 273
11.1 Introduction 273
11.2 Basic Lung Mechanics vs. Mechanical Ventilation 275
11.3 Ventilator Induced Inflammatory Response 276
11.4 Protein-Protein Interactions 277
11.5 Unfolding of p130Cas as a Mechanosensor 278
11.6 AFAP as an Activator of Src PTK 280
11.7 Src PKT Activation by Multiple Physical Forces 283
11.8 Blocking Src PTK as a Potential Therapy for VILI 285
11.9 Conclusions and Perspective 286
References 287
Part V Mechanosensing and Mechanotransduction in Bone and Joint Tissues 292
12 Cellular Mechanisms of Mechanotransduction in Bone 293
12.1 Introduction 294
12.2 Detection of Mechanical Stimuli 294
12.2.1 Focal Adhesions and the Mechanosome Hypothesis 294
12.2.2 Ion Channel and Purinergic Signaling in Bone 296
12.2.3 Primary Cilia 297
12.3 Propagation of Mechanical Signals in Bone Cells 298
12.3.1 Focal Adhesion Kinase (FAK) 298
12.3.2 Wnt/-Catenin/Sclerostin 300
12.3.3 Gap Junctions 301
12.3.4 NFAT 302
12.3.5 Nitric Oxide cGMP-Dependent Kinases 302
12.3.6 Nmp4/CIZ 303
12.4 Conclusions and Perspectives 304
References 305
13 The Mechanosensitivity of Cells in Joint Tissues: Role in the Pathogenesis of Joint Diseases 313
13.1 Introduction 313
13.2 Mechanical Stimuli and Chondrocyte Metabolism 314
13.2.1 Mechanical Stimuli and Cartilage Matrix Remodeling 314
13.2.2 Chondrocyte Mechanotransduction 316
13.3 Mechanical Stimuli and Subchondral Bone 317
13.4 Others Joint Tissues Mechanosensitivity 322
13.5 Conclusion and Perspectives 324
References 324
Part VI Mechanotransduction of Sensor System 330
14 Primary Cilia are Mechanosensory Organelles in Vestibular Tissues 331
14.1 Introduction 331
14.1.1 Building Blocks of Cilia 334
14.1.2 Cilia and Vestibular Organs 335
14.2 Cilia as Fluid Sensors 339
14.2.1 Structural Proteins 340
14.2.2 Sensory Proteins 340
14.3 Mechanosensory Cilia Function 342
14.3.1 Hensen's Node 342
14.3.2 Kidney 343
14.3.3 Liver 344
14.3.4 Pancreas 346
14.3.5 Bone 346
14.3.6 Cardiovascular 347
14.4 Conclusion and Perspective 349
References 350
Part VII Mechanosensitivity and Mechanotransductionin Blood Cells 365
15 Mechanosensitive K+ Channels in Mouse B Lymphocytes: PLC-Mediated Release of TREK-2 from Inhibition by PIP2 366
15.1 Introduction 366
15.1.1 K+ Channels Modulating the Ca 2+ Signal in Lymphocytes 366
15.1.2 Mechanical Stress and Ion Channels in Lymphocytes 367
15.2 Mechanosensitive Background-Type K+ Channels in B Lymphocytes 368
15.2.1 Discovery of Background-Type K+ Channels in B Lymphocytes 368
15.2.2 Stretch-Dependent Activation of LK bg in B Lymphocytes 369
15.2.3 Regulation of LK bg/TREK-2 by PIP 2 371
15.2.4 Dual Sensitivity of LK bg/TREK-2 to PIP 2 373
15.3 Mechanosensitivity of TREK-2/LK bg in B Cells 375
15.4 PLC-Dependent Mechanosensitivity of Cells 378
15.5 Role of Mechanosensitive TREK-2 in B Cells 378
References 379
Index 382
| Erscheint lt. Verlag | 18.11.2010 |
|---|---|
| Reihe/Serie | Mechanosensitivity in Cells and Tissues | Mechanosensitivity in Cells and Tissues |
| Zusatzinfo | XXIV, 371 p. |
| Verlagsort | Dordrecht |
| Sprache | englisch |
| Themenwelt | Medizinische Fachgebiete ► Innere Medizin ► Kardiologie / Angiologie |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie | |
| Naturwissenschaften ► Biologie ► Biochemie | |
| Naturwissenschaften ► Biologie ► Mikrobiologie / Immunologie | |
| Naturwissenschaften ► Biologie ► Zellbiologie | |
| Technik | |
| Schlagworte | Cytoskeleton • Mechanically gated channels • Mechanosensitivity • Mechanotransduction • Stretch-induced signaling cascades |
| ISBN-10 | 90-481-9881-X / 904819881X |
| ISBN-13 | 978-90-481-9881-8 / 9789048198818 |
| Haben Sie eine Frage zum Produkt? |
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