Structure and Function of the Extracellular Matrix

He earned an MS in physics (1982) and PhD in biomechanics and respiratory physiology (1987). He is now a professor of Biomedical Engineering at Boston University. Over the last 3 decades, he has worked in various areas of the life sciences including respiratory and vascular physiology and biomechanics, cell and tissue mechanics, computational fluid and solid mechanics applied to various physiological problems and complexity in physiology and biology. He has published over 230 papers, reviews and book chapters. He developed 3 relevant courses: 1) Structure and function of the extracellular matrix (BE 549); 2) Respiratory and cardiovascular engineering (BE 508); and 3) Nonlinear systems in biomedical engineering (BE 567).

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