Structure and Function of the Extracellular Matrix: A Multiscale Quantitative Approach introduces biomechanics and biophysics with applications to understand the biological function of the extracellular matrix in health and disease. A general multiscale approach is followed by investigating behavior from the scale of single molecules, through fibrils and fibers, to tissues of various organ systems. Through mathematical models and structural information, quantitative description of the extracellular matrix function is derived with tissue specific details. The book introduces the properties and organization of extracellular matrix components and quantitative models of the matrix, and guides the reader through predicting functional properties.�
This book integrates evolutionary biology with multiscale structure to quantitatively understand the function of the extracellular matrix. This approach allows a fresh look into normal functioning as well as the pathological alterations of the extracellular matrix. Professor Suki's book is written to be useful to undergraduates, graduate students, and researchers interested in the quantitative aspects of the extracellular matrix. Researchers working in mechanotransduction, respiratory and cardiovascular mechanics, and multiscale biomechanics of tendon, cartilage, skin, and bone may also be interested in this book.
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Table of Contents
Preface ix
Definition of symbols xi
1. Introduction to structure-function relationships
What is structure? 1
What is function? 1
What are structure-function relations? 2
The multiscale nature of structure-function relations 3
Evolutionary aspects 4
Implications for science and medicine 5
References 6
2. Extracellular matrix background material: Building blocks, general structure, mechanics, relation to cells, and evolutionary aspects
The building blocks and the structure of proteins 9
General properties and organization of the ECM 11
Mechanical forces, stresses, and stiffness 14
Relation of the ECM to cells 19
ECM and evolution 21
References 25
3. The collagen molecule
Collagen classification 29
A brief evolutionary history of the collagen family 31
Structure of the collagen molecule 33
Biosynthesis 35
Collagen functions 36
Collagen binding properties 38
Collagen elasticity 39
Polymer-based modeling: The mechanical properties of the molecule 44
Structural models of the collagen molecule 45
Effects of mutations on molecular structure and function 49
References 52
4. Collagen supramolecular structures: Evolution, organization, and biogenesis
Evolution of the fibril and the diversification of the collagen family 56
Multiscale nature of fibril structure 59
Network structure of type IV collagen 62
Fibril formation 64
Modeling fibril growth 67
References 73
5. Collagen suprastructures: The data and the models Structure and function of type IV collagen networks 78
Quantitative analysis of structure-function relations in the glomerular basement membrane of the kidney 80
Structure-function of elastic networks from the point of view of percolation: Implications for tissue engineering 85
Microscopic structure-function relations of the collagen fibril 88
Multiscale mechanical properties of the collagen fibril: The data 91
Modeling fibril function: From simple to complex 96
Is fibril viscoelasticity a signature of hidden complexity? 100
References 108
6. Selected examples of tissue-level collagen suprastructures: Tendon, bone, and skin
Basic structure and function of the tendon 113
Modeling the recruitment of wavy fibrils during tendon stretching 114
Modeling tendon rupture 119
A brief introduction to the evolutionarily shaped structure and function of the bone 120
Examples of multiscale structure-function relation in bones 123
The evolution and basic function of the skin 128
Multiscale mechanics and tear resistance of the skin 130
A note on the biological significance of recruitment 136
References 139
7. Small leucine-rich proteoglycans: The tiny controllers of the extracellular matrix
Basic structure and evolution of SLRPs 143
Biological functions of SLRPs 146
The PG interaction network 149
Physiological functions of SLRPs 151
Influence of GAGs on lung parenchymal mechanics 155
Summary 159
References 159
8. Hyaluronan and hyalectans: The good, the bad, and the ugly
Evolutionary history 166
The structure of the HA-hyalectan aggregate 167
Binding and molecular to cellular functions 171
Microscale physiological functions 173
Structure and function of the endothelial glycocalyx 176
Physiological functions 179
The bad and the ugly 184
Summary 187
References 188
9. Elastic fibers: The near ideal linear springs of the extracellular matrix
Evolution of elastin 194
The tropoelastin gene structure 196
Structure, disorder, and aggregation 197
Mechanical properties of tropoelastin 201
Microfibrils 204
Elastogenesis: How to build a network of elastic fibers 206
Elastic fibers: Are they ideal linear springs? 208
A brief summary on organ-level function and its breakdown 217
Final notes on the near ideal spring 219
References 223
10. Modeling maintenance and repair: The matrix loaded
Evolution of homeostasis and repair 230
A continuum approach to ECM growth and remodeling 235
Dynamics of homeostasis and structural remodeling 237
Fluctuation-driven homeostasis 240
A toy model of self-healing 243
Agent-based modeling: The network paradigm 245
The uninvited aging: Maintenance and repair slipping out of control 249
What have we learned? 250
References 251
11. Outlook
Index 259
