Structure and Function of the Extracellular Matrix

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.