Cell and tissue engineering / redactor, Bojana Obradović.

Includes bibliographical references and index.

1. CREATION OF LIVING TISSUE: AN ENGINEERING FEAT 1
1.1. OPTIONS ON THE TABLE 1
1.2. COMPLEXITY OF BIOLOGICAL ORGANS 2
1.3. SIZING UP THE CHALLENGE 4
1.4. TISSUE ENGINEERING
2. CLASSICAL AND QUANTUM INFORMATION PROCESSING
IN DNA-PROTEIN CODING 9
2.1. INTRODUCTION 9
2.2 BASIC FACTS 11
2.3. DNA-PROTEIN SYSTEM MODELING 13
2.3.1. Energy approach 13
2.3.2. Information approach 14
2.3.3. Synergy approach 16
2.4 HOW DOES THE DNA-PROTEIN INFORMATION SYSTEM WORK? 17
2.4.1. New considerations in mechanisms of DNA action 17
2.4.2. Hydrogen bonds as a central enigma of life 18
2.4.3. Synergy of classical and quantum information 19
2.4.4. Violation of the synergetic DNA-protein information channel and cancer 21
2.5. SUMMARY
3. UNRAVELING THE MEMBRANE FUSION IN SECRETORY CELLS AT THE
NM-LEVEL: A NANOBIOENGINEERING APPROACH 27
3.1. INTRODUCTION 27
3.2. POROSOME: A NEW CELLULAR STRUCTURE 30
3.3. POROSOME: ISOLATION AND RECONSTITUTION 34
3.4. SNARE-INDUCED MEMBRANE FUSION 37
3.5. REGULATION OF SECRETORY VESICLE SWELLING: INVOLVEMENT IN
EXPULSION OF VESICULAR CONTENTS 39
3.6. MOLECULAR UNDERSTANDING OF CELL SECRETION 40

4. BIOPHYSICAL AND BIOCHEMICAL DETERMINANTS OF CONTRACTILE
FORCE GENERATION, REGULATION, AND FUNCTION 44
4.1. THE FUNDAMENTAL PROBLEM OF MUSCLE CONTRACTION 44
4.1.1 Structure of skeletal muscle 44
4.1.2. What makes muscles shorten? 46
4.1.3. The cross-bridge cycle 47
4.1.4. Swinging lever arm and power stroke 49
4.1.5. Atomic structures of actin and myosin 50
4.2. BUILDING A COMPREHENSIVE MODEL OF MUSCLE CONTRACTION 51
4.2.1. What is the appropriate model to start with? 52
4.2.2 Energy landscape of myosin binding to actin 53
4.2.3. Extensibility of actin and myosin filaments 54
4.2.4. Calcium regulation 55
4.3 MATHEMATICAL FOUNDATIONS OF SLIDING FILA-MENT THEORY AND
COMPUTATIONAL METHODS THEORETICAL MODELS OF MUSCLE
CONTRACTION 57
4.3.1. Basic concepts and definitions
4.3.2. A probabilistic formulation of cross-bridge kinetics 58
4.3.3. Rules for strain-dependent cross-bridge transition rates 60
4.3.4. Stochastic strain dependent binding in 3D sarcomere lattice 62
4.3.5. Probabilistic and stochastic numerical solutions 62
4.4. THEORETICAL MODELS OF MUSCLE CONTRACTION 63
4.4.1 Huxley's sliding filament model in extensible filament lattice 63
4.4.2. Stochastic strain dependent binding in 3D sarcomere lattice 69
4.4.3. Thin filament regulation in skeletal muscle 72
4.4.4. The latch regulatory scheme in smooth muscle
5. CYTOSKELETAL PRESTRESS AS A DETERMINANT OF
DEFORMABILITY AND RHEOLOGY OF ADHERENT CELLS 92
5.1. INTRODUCTION 92
5.2. WHAT IS PRESTRESS? 93
5.3. STATICS: PRESTRESS AND CELL DEFORMABILITY 94
5.3.1. Measurements of cytoskeletal prestress and stiffness 96
5.3.1.1. Traction Microscopy 96
5.3.1.2. Magnetic Twisting Cytometry 97
5.3.2. Modeling of the steady-state mechanical behavior of the CSK 98
5.3.2.2. Prestress induced stiffness of the CSK 101
5.4. DYNAMICS: PRESTRESS AND CELL RHEOLOGY 103
5.4.1. Mechanisms that link cytoskeletal prestress to rheology 106
5.4.1.1. Tensegrity and cytoskeletal rheology 106
5.4.1.2. Myosin cross-bridge kinetics 108
5.4.1.3. Cytoskeletal remodeling 108
5.4.1.4. Activation energy 108
5.4.1.5. Actin network dynamics 109
5.4.1.6. Dynamics of individual polymer chains under sustained tension 110
5.5. CONCLUSIONS

6. CELL AND TISSUE ORGANIZATION IN SOFT MATERIALS: INSIGHT
FROM MATHEMATICAL AND BIOPHYSICAL MODELLING 119
6.1. INTRODUCTION 119
6.1.1. Overview of cell and tissue organization principles for adherent cells 119
6.1.2. Classification of mechanical signals and biological responses 120
6.1.3. Effect of substrate mechanics on cell behavior 121
6.1.4. Sensing substrate mechanics: Active mechanosensing 121
6.2. A PRIMER ON ELASTICITY THEORY 123
6.3. TOWARDS A SYSTEM UNDERSTANDING OF THE INFLUENCE OF
SUBSTRATE MECHANICS ON CELL AND TISSUE ORGANIZATION 125
6.3.1. Modeling cellular scale effects 125
6.3.2. Modeling tissue scale effects 128
6.3.3. Modeling subcellular scale effects 130
6.4. OUTLOOK 132
7. SUBSTRATE STRETCHING AND ORIENTATION OF ACTIVE CELLS AS A
STABILITY PROBLEM 135
7.1. INTRODUCTION 135
7.2. MECHANICS PRELIMINARIES 139
7.3. THE NONLINEAR HOMOGENEOUS STRAIN FIELD
OF A STRESS FIBER 142
7.4. THE EQUILIBRIUM PLACEMENTS OF THE STRESS-FIBERS 145
7.5. GLOBALLY STABLE EQUILIBRIUM PLACEMENTS
7.6. APPLICATIONS 151
7.7. DISCUSSION
8. ROLES OF MECHANICAL FORCES AND EXTRACELLULAR MATRIX
PROPERTIES IN CELLULAR SIGNALING IN THE LUNG 158
8.1. INTRODUCTION 158
8.2. MAIN CONSTITUENTS OF THE LUNG CONNECTIVE TISSUE 160
8.2.1. Properties of collagens 160
8.2.2. Properties of elastic fibers 161
8.2.3. Properties of proteoglycans 161
8.2.4. Interstitial cells 162
8.2.5. Air-liquid interface and surface tension 163
8.2.6. Interaction among the tissue components 163
8.3. MECHANICAL PROPERTIES OF THE NORMAL LUNG 164
8.3.1. Molecular, fibril and fiber elasticity 164
8.3.2. Elasticity of lung collagen, alveolar wall, tissue strip and whole lung 166
8.4. EFFECTS OF MECHANICAL FORCES ON THE LUNG PARENCHYMA 168
8.4.1. Mechanical forces, cell signaling and biomechanical properties of the ECM 168
8.4.2. Mechanical forces in the diseased lung 170
8.5. SUMMARY 172
9. ENZYME SIGNALING: IMPLICATIONS FOR TISSUE ENGINEERING 179
9.1. INTRODUCTION 180
9.2. GENERAL PROPERTIES OF ENZYMES 181
9.3. METALLOPROTEINASES IN SIGNALING 183
9.3.1. MMPs in diseases 183
9.3.2. Types and Structure of MMPs 184
9.3.3. Activation and inhibition of MMPs 187
9.3.4. Pharmacological manipulations of MMPs 188
9.4. GENERAL CONSIDERATIONS FOR TISSUE ENGINEERING

10. HYDROGELS IN TISSUE ENGINEERING 197
10.1. INTRODUCTION 197
10.2. WHAT IS A HYDROGEL? 199
10.3. METHODS OF PREPARATION 200
10.3.1. Chemical hydrogel preparation 200
10.3.2. Physical hydrogel preparation 201
10.3.2.1. Hydrogels obtained by ionic interactions 202
10.3.2.2. Hydrogels obtained by crystallization 202
10.3.2.3. Hydrogels obtained from amphiphilic block and graft co-polymers 203
10.3.2.4. Hydrogels obtained by hydrogen bond interactions 204
10.3.2.5. Hydrogels obtained by protein interactions 204
10.4. HYDROGEL PROPERTIES 205
10.4.1. Swelling 205
10.4.2. Responsive hydrogels 206
10.4.3. Surface properties 207
10.4.4. Degradability 208
10.5. METHODS OF CHARACTERIZATION 208
10.6. BIOMEDICAL / TISSUE ENGINEERING APPLICATIONS 209
11. BIOREACTORS IN TISSUE ENGINEERING 217
11.1. INTRODUCTION: WHAT ARE TISSUE-ENGINEERING BIOREACTORS? 217
11.2. MASS TRANSPORT CONSIDERATIONS
11.3. BIOPHYSICAL REGULATION 219
11.3.1. Engineered Bone 219
11.3.2. Engineered Cartilage 221
11.3.3. Engineered Myocardium 223
11.4. SUMMARY 223
12. APPROACHES TO MATHEMATICAL MODELING OF TISSUE
ENGINEERING SYSTEMS 228
12.1. INTRODUCTION 228
12.2. CHARACTERIZATION OF IN VITRO CULTIVATING CONDITIONS 231
12.2.1. Hydrodynamic environment 232
12.2.2. Modeling of mass transfer 234
12.2.2.1. Mass transport through the tissue by diffusion 234
12.2.2.2. Enhancement of mass transport through the tissue by convection 239
12.3. CORRELATIONS OF CULTIVATING CONDITIONS WITH THE CELL
RESPONSE AND TISSUE PROPERTIES 242
12.3.1. Correlations of hydrodynamic conditions with the tissue growth 242
12.3.2. Mathematical model of GAG accumulation in engineered cartilage constructs244
12.4. CONCLUSION 247
13. COMPUTATIONAL MODELING OF TISSUE SELF-ASSEMBLY 251
13.1. THE MODELING APPROACH TO MORPHOGENESIS 251
13.2. IN SILICO TISSUE ENGINEERING 253
13.3. A LATTICE MODEL OF LIVING TISSUES 254
13.4. MONTE CARLO SIMULATIONS OF THE SELF
-ASSEMBLY OF LIVING CELLS 258
Index