“Cell and Tissue Engineering” introduces the principles and new approaches in cell and tissue engineering. It includes both the fundamentals and the current trends in cell and tissue engineering, in a way useful both to a novice and an expert in the field. The book is composed of 13 chapters all of which are written by the leading experts. It is organized to gradually assemble an insight in cell and tissue function starting form a molecular nano-level, extending to a cellular micro-level and finishing at the tissue macro-level. In specific, biological, physiological, biophysical, biochemical, medical, and engineering aspects are covered from the standpoint of the development of functional substitutes of biological tissues for potential clinical use. Topics in the area of cell engineering include cell membrane biophysics, structure and function of the cytoskeleton, cell-extracellular matrix interactions, and mechanotransduction. In the area of tissue engineering the focus is on the in vitro cultivation of functional tissue equivalents based on the integrated use of isolated cells, biomaterials, and bioreactors. The book also reviews novel techniques for cell and tissue imaging and characterization, some of which are described in detail such as atomic force microscopy. Finally, mathematical modeling methods are presented as valuable and indispensable tools in cell and tissue engineering. Numerous illustrations enhance the quality and ease of use of the presented material. CoverPage......Page 1 Cell and Tissue Engineering......Page 2 PREFACE......Page 5 CONTENTS......Page 7 1.1. OPTIONS ON THE TABLE......Page 12 1.2. COMPLEXITY OF BIOLOGICAL ORGANS......Page 13 1.3. SIZING UP THE CHALLENGE......Page 15 1.4. TISSUE ENGINEERING......Page 17 2.1. INTRODUCTION......Page 20 2.2 BASIC FACTS......Page 22 2.3.1. Energy approach......Page 24 2.3.2. Information approach......Page 25 2.3.3. Synergy approach......Page 27 2.4.1. New considerations in mechanisms of DNA action......Page 28 2.4.2. Hydrogen bonds as a central enigma of life......Page 29 2.4.3. Synergy of classical and quantum information......Page 30 2.4.4. Violation of the synergetic DNA-protein information channel and cancer......Page 32 2.5. SUMMARY......Page 34 References......Page 35 3.1. INTRODUCTION......Page 38 3.2. POROSOME: A NEW CELLULAR STRUCTURE......Page 41 3.3. POROSOME: ISOLATION AND RECONSTITUTION......Page 45 3.4. SNARE-INDUCED MEMBRANE FUSION......Page 48 3.5. REGULATION OF SECRETORY VESICLE SWELLING: INVOLVEMENT IN EXPULSION OF VESICULAR CONTENTS......Page 50 3.6. MOLECULAR UNDERSTANDING OF CELL SECRETION......Page 51 References......Page 52 4.1.1 Structure of skeletal muscle......Page 55 4.1.2. What makes muscles shorten?......Page 57 4.1.3. The cross-bridge cycle......Page 58 4.1.4. Swinging lever arm and power stroke......Page 60 4.1.5. Atomic structures of actin and myosin......Page 61 4.2. BUILDING A COMPREHENSIVE MODEL OF MUSCLE CONTRACTION......Page 62 4.2.1. What is the appropriate model to start with?......Page 63 4.2.2 Energy landscape of myosin binding to actin......Page 64 4.2.3. Extensibility of actin and myosin filaments......Page 65 4.2.4. Calcium regulation......Page 66 4.3.1. Basic concepts and definitions......Page 68 4.3.2. A probabilistic formulation of cross-bridge kinetics......Page 69 4.3.3. Rules for strain-dependent cross-bridge transition rates......Page 71 4.3.5. Probabilistic and stochastic numerical solutions......Page 73 4.4.1 Huxley’s sliding filament model in extensible filament lattice......Page 74 4.4.2. Stochastic strain dependent binding in 3D sarcomere lattice......Page 80 4.4.3. Thin filament regulation in skeletal muscle......Page 83 4.4.4. The latch regulatory scheme in smooth muscle......Page 90 References......Page 97 5.1. INTRODUCTION......Page 103 5.2. WHAT IS PRESTRESS?......Page 104 5.3. STATICS: PRESTRESS AND CELL DEFORMABILITY......Page 105 5.3.1.1. Traction Microscopy......Page 107 5.3.1.2. Magnetic Twisting Cytometry......Page 108 5.3.2. Modeling of the steady-state mechanical behavior of the CSK......Page 109 5.3.2.1. Force balance between actin microfilaments, microtubules and the ECM......Page 110 5.3.2.2. Prestress induced stiffness of the CSK......Page 112 5.4. DYNAMICS: PRESTRESS AND CELL RHEOLOGY......Page 114 5.4.1.1. Tensegrity and cytoskeletal rheology......Page 117 5.4.1.4. Activation energy......Page 119 5.4.1.5. Actin network dynamics......Page 120 5.4.1.6. Dynamics of individual polymer chains under sustained tension......Page 121 5.5. CONCLUSIONS......Page 124 References......Page 125 6.1.1. Overview of cell and tissue organization principles foradherent cells......Page 130 6.1.2. Classification of mechanical signals and biological responses......Page 131 6.1.4. Sensing substrate mechanics: Active mechanosensing......Page 132 6.2. A PRIMER ON ELASTICITY THEORY......Page 134 a) Modeling mechanical activity: The force multipole expansion......Page 136 b) Cell organization in soft materials: preference for effective stiffness......Page 137 b) Pattern formation due to elastic interactions......Page 139 c) Polarization and effective material properties......Page 140 a) The two-spring model of active mechanosensing......Page 141 b) Theoretical models for mechanotransduction at cell matrix contacts......Page 142 References and suggested readings......Page 143 7.1. INTRODUCTION......Page 146 7.2. MECHANICS PRELIMINARIES.......Page 150 7.3. THE NONLINEAR HOMOGENEOUS STRAIN FIELD OF A STRESS FIBER......Page 153 7.4. THE EQUILIBRIUM PLACEMENTS OF THE STRESSFIBERS......Page 156 7.5. GLOBALLY STABLE EQUILIBRIUM PLACEMENTS......Page 159 7.6. APPLICATIONS......Page 162 7.6. DISCUSSION......Page 163 References......Page 164 APPENDIX......Page 165 Extension of a twin spring problem......Page 166 8.1. INTRODUCTION......Page 169 8.2.1. Properties of collagens......Page 171 8.2.3. Properties of proteoglycans......Page 172 8.2.4. Interstitial cells......Page 173 8.2.6. Interaction among the tissue components......Page 174 8.3.1. Molecular, fibril and fiber elasticity......Page 175 8.3.2. Elasticity of lung collagen, alveolar wall, tissue strip and whole lung......Page 177 8.4.1. Mechanical forces, cell signaling and biomechanical propertiesof the ECM......Page 179 8.4.2. Mechanical forces in the diseased lung......Page 181 8.5. SUMMARY......Page 183 References......Page 184 9 ENZYME SIGNALING: IMPLICATIONS FOR TISSUE ENGINEERING......Page 190 9.1. INTRODUCTION......Page 191 9.2. GENERAL PROPERTIES OF ENZYMES......Page 192 9.3.1. MMPs in diseases......Page 194 9.3.2. Types and Structure of MMPs......Page 195 9.3.3. Activation and inhibition of MMPs......Page 198 9.3.4. Pharmacological manipulations of MMPs......Page 199 9.4. GENERAL CONSIDERATIONS FOR TISSUE ENGINEERING......Page 201 References and suggested readings......Page 204 10.1. INTRODUCTION......Page 208 10.2. WHAT IS A HYDROGEL?......Page 210 10.3.1. Chemical hydrogel preparation......Page 211 10.3.2. Physical hydrogel preparation......Page 212 10.4.1. Swelling......Page 216 10.4.2. Responsive hydrogels......Page 217 10.4.3. Surface properties......Page 218 10.5. METHODS OF CHARACTERIZATION......Page 219 10.6. BIOMEDICAL / TISSUE ENGINEERING APPLICATIONS......Page 220 References and suggested readings......Page 223 11.1. INTRODUCTION: WHAT ARE TISSUE-ENGINEERING BIOREACTORS?......Page 228 11.2. MASS TRANSPORT CONSIDERATIONS......Page 229 11.3.1. Engineered Bone......Page 230 11.3.2. Engineered Cartilage......Page 232 11.4. SUMMARY......Page 234 Acknowledgements......Page 235 References......Page 236 12.1. INTRODUCTION......Page 239 12.2. CHARACTERIZATION OF IN VITRO CULTIVATING CONDITIONS ......Page 242 12.2.1. Hydrodynamic environment......Page 243 12.2.2.1. Mass transport through the tissue by diffusion......Page 245 12.2.2.2. Enhancement of mass transport through the tissue by convection......Page 250 12.3.1. Correlations of hydrodynamic conditions with the tissue growth......Page 253 12.3.2. Mathematical model of GAG accumulation in engineered cartilage constructs......Page 255 12.4. CONCLUSION......Page 258 References......Page 259 13.1. THE MODELING APPROACH TO MORPHOGENESIS......Page 262 13.2. IN SILICO TISSUE ENGINEERING......Page 264 13.3. A LATTICE MODEL OF LIVING TISSUES......Page 265 13.4. MONTE CARLO SIMULATIONS OF THE SELF-ASSEMBLY OF LIVING CELLS......Page 269 References......Page 274 INDEX......Page 284