Cytoskeletal Mechanics: Models and Measurements in Cell Mechanics (Cambridge Texts in Biomedical Engineering)

The purpose of this book is to present a full spectrum of views on current approaches to modeling cell mechanics. In part, this diversity of opinions stems from the different backgrounds of those who have contributed to the field. The authors of this book come from the biophysics, bioengineering, and physical chemistry communities, and each joins the discussion with their own unique perspective on biological systems. Consequently, the approaches range from finite element methods as commonly used in continuum mechanics, to models of the cytoskeleton as a cross-linked polymer network, to models of glassy materials and gels. Studies reflect both the static, instantaneous nature of the structure as well as its dynamic nature due to polymerization and the full array of biological processes. It is unlikely that a single, unifying approach will evolve from this diversity, in part because of the complexity of the phenomena underlying the mechanical properties of the cell. It is our hope, however, that a better appreciation of the various perspectives will lead to a more highly coordinated approach to these essential problems, and might facilitate discussions among those with differing views. Cover 1 Half-title 3 Title 5 Copyright 6 Contents 7 Contributors 9 Preface 11 1 Introduction, with the biological basis for cell mechanics 13 Introduction 13 The role of cell mechanics in biological function 14 Maintenance of cell shape 14 Cell migration 16 Mechanosensing 17 Stress responses and the role of mechanical forces in disease 18 Active cell contraction 19 Structural anatomy of a cell 19 The extracellular matrix and its attachment to cells 21 Transmission of force to the cytoskeleton and the role of the lipid bilayer 21 Intracellular structures 22 Overview 27 References 27 2 Experimental measurements of intracellular mechanics 30 Introduction 30 Forces to which cells are exposed in a biological context 31 Methods to measure intracellular rheology by macrorheology, diffusion, and sedimentation 31 Whole cell aggregates 32 Sedimentation of particles 32 Diffusion 33 Mechanical indentation of the cell surface 34 Glass microneedles 34 Cell poker 34 Atomic force microscopy 37 Mechanical tension applied to the cell membrane 38 Shearing and compression between microplates 40 Fluid flow 40 Optical traps 42 Magnetic methods 44 Pulling by magnetic field gradients 46 Twisting of magnetized particles on the cell surface and interior 47 Passive microrheology 48 Optically detected individual probes 49 One-particle method 49 Two-particle methods 50 Dynamic light scattering and diffusing wave spectroscopy 51 Fluorescence correlation spectroscopy 53 Optical stretcher 54 Acoustic microscopy 54 Outstanding issues and future directions 55 References 55 3 The cytoskeleton as a soft glassy material 62 Introduction 62 Experimental findings in living cells 63 Magnetic Twisting Cytometry (MTC) 63 Measurements of cell mechanics 64 Frequency dependence of g' and g" 66 The structural damping equation 67 Reduction of variables 68 Universality 70 Scaling the data 71 Collapse onto master curves 72 Theory of soft glassy rheology 74 What are soft glassy materials 74 Sollich’s theory of SGMs 75 Soft glassy rheology and structural damping 76 Open questions 76 Biological insights from SGR theory 77 Malleability of airway smooth muscle 77 Conclusion 80 References 80 4 Continuum elastic or viscoelastic models for the cell 83 Introduction 83 Purpose of continuum models 84 Principles of continuum models 87 Boundary conditions 88 Mechanical and material characteristics 88 Example of studied cell types 90 Blood cells: leukocytes and erythrocytes 90 Adherent cells: fibrobasts, epithelial cells, and endothelial cells 91 Limitations of continuum model 93 Conclusion 93 References 94 5 Multiphasic models of cell mechanics 96 Introduction 96 Biphasic (solid–fluid) models of cell mechanics 97 Biphasic poroviscoelastic models of cell mechanics 99 Multiphasic and triphasic models (solid–fluid–ion) 100 Analysis of cell mechanical tests 101 Micropipette aspiration 102 Cells 102 Biphasic properties of the pericellular matrix 104 Indentation studies of cell multiphasic properties 106 Analysis of cell–matrix interactions using multiphasic models 108 Summary 110 References 111 6 Models of cytoskeletal mechanics based on tensegrity 115 Introduction 115 The cellular tensegrity model 116 Definitions, basic mechanisms, and properties of tensegrity structures 117 The cellular tensegrity model 118 Do living cells behave as predicted by the tensegrity model? 119 Circumstantial evidence 119 Prestress-induced stiffening 121 Action at a distance 122 Do microtubules carry compression? 124 The role of intermediate filaments 125 Summary 126 Examples of mathematical models of the cytoskeleton based on tensegrity 126 The cortical membrane model 127 Tensed cable nets 128 Cable-and-strut model 130 Summary 133 Tensegrity and cellular dynamics 133 Conclusion 136 Acknowledgement 137 References 137 7 Cells, gels, and mechanics 141 Introduction 141 Problems with the aqueous-solution-based paradigm 142 Cells as gels 144 Cell dynamics 147 Gels and motion 150 Secretion 151 Muscle contraction 152 Conclusion 159 Acknowledgement 159 References 159 8 Polymer-based models of cytoskeletal networks 164 Introduction 164 Single-filament properties 166 The worm-like chain model 167 Force-extension of single chains 168 Dynamics of single chains 172 Solutions of semiflexible polymer 174 Network elasticity 175 Nonlinear response 177 Discussion 179 References 180 9 Cell dynamics and the actin cytoskeleton 182 Introduction: The role of actin in the cell 182 Interaction of the cell cytoskeleton with the outside environment 184 Properties of actin filaments 186 The role of filamin A (FLNa) 187 The role of cytoskeletal structure 188 Actin mechanics 189 Actin dynamics 192 The emergence of actin dynamics 192 The intrinsic dynamics of actin 193 Regulation of dynamics by actin-binding proteins 195 ADF/cofilin: targeting the rate-limiting step in the actin cycle 195 Profilin: a multifunctional protein to close the loop 197 Arp2/3 complex and formins: making filaments anew 197 Capping protein: ‘decommissioning’ the old 199 Gelsolin: rapid remodeling in one or two steps 199 β4-thymosin: accounting (sometimes) for the other half 200 Dynamic actin in crawling cells 200 Actin in the leading edge 201 Monomer recycling: the other ‘actin dynamics’ 203 The biophysics of actin-based pushing 205 Conclusion 207 Acknowledgements 208 References 208 10 Active cellular protrusion: continuum theories and models 216 Cellular protrusion: the standard cartoon 216 The RIF formalism 217 Mass conservation 218 Momentum conservation 219 Boundary conditions 220 Cytoskeletal theories of cellular protrusion 221 Network–membrane interactions 222 Network dynamics near the membrane 224 Special cases of network–membrane interaction: polymerization force, brownian and motor ratchets 225 Network–network interactions 225 Network dynamics with swelling 227 Other theories of protrusion 227 Numerical implementation of the RIF formalism 229 An example of cellular protrusion 230 Protrusion driven by membrane–cytoskeleton repulsion 231 Protrusion driven by cytoskeletal swelling 232 Discussion 233 Conclusions 234 References 235 11 Summary 237 References 241 Index 243 Cover......Page 1 Half-title......Page 3 Title......Page 5 Copyright......Page 6 Contents......Page 7 Contributors......Page 9 Preface......Page 11 Introduction......Page 13 Maintenance of cell shape......Page 14 Cell migration......Page 16 Mechanosensing......Page 17 Stress responses and the role of mechanical forces in disease......Page 18 Structural anatomy of a cell......Page 19 Transmission of force to the cytoskeleton and the role of the lipid bilayer......Page 21 Intracellular structures......Page 22 References......Page 27 Introduction......Page 30 Methods to measure intracellular rheology by macrorheology, diffusion, and sedimentation......Page 31 Sedimentation of particles......Page 32 Diffusion......Page 33 Cell poker......Page 34 Atomic force microscopy......Page 37 Mechanical tension applied to the cell membrane......Page 38 Fluid flow......Page 40 Optical traps......Page 42 Magnetic methods......Page 44 Pulling by magnetic field gradients......Page 46 Twisting of magnetized particles on the cell surface and interior......Page 47 Passive microrheology......Page 48 One-particle method......Page 49 Two-particle methods......Page 50 Dynamic light scattering and diffusing wave spectroscopy......Page 51 Fluorescence correlation spectroscopy......Page 53 Acoustic microscopy......Page 54 References......Page 55 Introduction......Page 62 Magnetic Twisting Cytometry (MTC)......Page 63 Measurements of cell mechanics......Page 64 Frequency dependence of g' and g"......Page 66 The structural damping equation......Page 67 Reduction of variables......Page 68 Universality......Page 70 Scaling the data......Page 71 Collapse onto master curves......Page 72 What are soft glassy materials......Page 74 Sollich’s theory of SGMs......Page 75 Open questions......Page 76 Malleability of airway smooth muscle......Page 77 References......Page 80 Introduction......Page 83 Purpose of continuum models......Page 84 Principles of continuum models......Page 87 Mechanical and material characteristics......Page 88 Blood cells: leukocytes and erythrocytes......Page 90 Adherent cells: fibrobasts, epithelial cells, and endothelial cells......Page 91 Conclusion......Page 93 References......Page 94 Introduction......Page 96 Biphasic (solid–fluid) models of cell mechanics......Page 97 Biphasic poroviscoelastic models of cell mechanics......Page 99 Multiphasic and triphasic models (solid–fluid–ion)......Page 100 Analysis of cell mechanical tests......Page 101 Cells......Page 102 Biphasic properties of the pericellular matrix......Page 104 Indentation studies of cell multiphasic properties......Page 106 Analysis of cell–matrix interactions using multiphasic models......Page 108 Summary......Page 110 References......Page 111 Introduction......Page 115 The cellular tensegrity model......Page 116 Definitions, basic mechanisms, and properties of tensegrity structures......Page 117 The cellular tensegrity model......Page 118 Circumstantial evidence......Page 119 Prestress-induced stiffening......Page 121 Action at a distance......Page 122 Do microtubules carry compression?......Page 124 The role of intermediate filaments......Page 125 Examples of mathematical models of the cytoskeleton based on tensegrity......Page 126 The cortical membrane model......Page 127 Tensed cable nets......Page 128 Cable-and-strut model......Page 130 Tensegrity and cellular dynamics......Page 133 Conclusion......Page 136 References......Page 137 Introduction......Page 141 Problems with the aqueous-solution-based paradigm......Page 142 Cells as gels......Page 144 Cell dynamics......Page 147 Gels and motion......Page 150 Secretion......Page 151 Muscle contraction......Page 152 References......Page 159 Introduction......Page 164 Single-filament properties......Page 166 The worm-like chain model......Page 167 Force-extension of single chains......Page 168 Dynamics of single chains......Page 172 Solutions of semiflexible polymer......Page 174 Network elasticity......Page 175 Nonlinear response......Page 177 Discussion......Page 179 References......Page 180 Introduction: The role of actin in the cell......Page 182 Interaction of the cell cytoskeleton with the outside environment......Page 184 Properties of actin filaments......Page 186 The role of filamin A (FLNa)......Page 187 The role of cytoskeletal structure......Page 188 Actin mechanics......Page 189 The emergence of actin dynamics......Page 192 The intrinsic dynamics of actin......Page 193 ADF/cofilin: targeting the rate-limiting step in the actin cycle......Page 195 Arp2/3 complex and formins: making filaments anew......Page 197 Gelsolin: rapid remodeling in one or two steps......Page 199 Dynamic actin in crawling cells......Page 200 Actin in the leading edge......Page 201 Monomer recycling: the other ‘actin dynamics’......Page 203 The biophysics of actin-based pushing......Page 205 Conclusion......Page 207 References......Page 208 Cellular protrusion: the standard cartoon......Page 216 The RIF formalism......Page 217 Mass conservation......Page 218 Momentum conservation......Page 219 Boundary conditions......Page 220 Cytoskeletal theories of cellular protrusion......Page 221 Network–membrane interactions......Page 222 Network dynamics near the membrane......Page 224 Network–network interactions......Page 225 Other theories of protrusion......Page 227 Numerical implementation of the RIF formalism......Page 229 An example of cellular protrusion......Page 230 Protrusion driven by membrane–cytoskeleton repulsion......Page 231 Protrusion driven by cytoskeletal swelling......Page 232 Discussion......Page 233 Conclusions......Page 234 References......Page 235 11 Summary......Page 237 References......Page 241 Index......Page 243 This Book Presents A Full Spectrum Of Views On Current Approaches To Modeling Cell Mechanics. The Authors Of This Book Come From The Biophysics, Bioengineering, And Physical Chemistry Communities And Each Joins The Discussion With A Unique Perspective On Biological Systems. Consequently, The Approaches Range From Finite Element Methods Commonly Used In Continuum Mechanics To Models Of The Cytoskeleton As A Cross-linked Polymer Network To Models Of Glassy Materials And Gels. Studies Reflect Both The Static, Instantaneous Nature Of The Structure, As Well As Its Dynamic Nature Due To Polymerization And The Full Array Of Biological Processes. While It Is Unlikely That A Single Unifying Approach Will Evolve From This Diversity, It Is Our Hope That A Better Appreciation Of The Various Perspectives Will Lead To A Highly Coordinated Approach To Exploring The Essential Problems And Better Discussions Among Investigators With Differing Views.--jacket. Introduction, With The Biological Basis For Cell Mechanics / Roger D. Kamm And Mohammad R.k. Mofrad -- Experimental Measurements Of Intracellular Mechanics / Paul Janmey And Christoph Schmidt -- The Cytoskeleton As A Soft Glassy Material / Jeffrey Fredberg And Ben Fabry -- Continuum Elastic Or Viscoelastic Models For The Cell / Mohammed [sic] R.k. Mofrad, Helene Karcher, And Roger D. Kamm -- Multiphasic Models Of Cell Mechanics / Farshid Guilak ... [et Al.] -- Models Of Cytoskeletal Mechanics Based On Tensegrity / Dimitrije Stamenović -- Cells, Gels And Mechanics / Gerald H. Pollack -- Polymer-based Models Of Cytoskeletal Networks / F.c. Mackintosh -- Cell Dynamics And The Actin Cytoskeleton / James L. Mcgrath And C. Forbes Dewey, Jr. -- Active Cellular Motion : Continuum Theories And Models / Marc Herant And Micah Dembo. Edited By Mohammad R.k. Mofrad, Roger D. Kamm. Includes Bibliographical References And Index. This book presents a full spectrum of views on current approaches to modeling cell mechanics. The authors come from the biophysics, bioengineering and physical chemistry communities and each joins the discussion with a unique perspective on biological systems. Consequently, the approaches range from finite element methods commonly used in continuum mechanics to models of the cytoskeleton as a cross-linked polymer network to models of glassy materials and gels. Studies reflect both the static, instantaneous nature of the structure, as well as its dynamic nature due to polymerization and the full array of biological processes. While it is unlikely that a single unifying approach will evolve from this diversity, it is the hope that a better appreciation of the various perspectives will lead to a highly coordinated approach to exploring the essential problems and better discussions among investigators with differing views. Introduction, with the biological basis for cell mechanics / Roger D. Kamm and Mohammad R.K. Mofrad -- Experimental measurements of intracellular mechanics / Paul Janmey and Christoph Schmidt -- The cytoskeleton as a soft glassy material / Jeffrey Fredberg and Ben Fabry -- Continuum elastic or viscoelastic models for the cell / Mohammed [sic] R.K. Mofrad, Helene Karcher, and Roger D. Kamm -- Multiphasic models of cell mechanics / Farshid Guilak [und weitere] -- Models of cytoskeletal mechanics based on tensegrity / Dimitrije Stamenović -- Cells, gels and mechanics / Gerald H. Pollack -- Polymer-based models of cytoskeletal networks / F.C. MacKintosh -- Cell dynamics and the actin cytoskeleton / James L. McGrath and C. Forbes Dewey, Jr. -- Active cellular motion : continuum theories and models / Marc Herant and Micah Dembo