Table Of ContentMechanotransduction
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Mechanotransduction
Cell Signaling to Cell Response
PAUL A. SUNDARAM
University of PuertoRico,Mayagüez, PuertoRico
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Dedication
My wife, Fabiola, who is my perfect complement,
my true companion, without whom I would be incomplete.
My children, Paola Alejandra and Julian Patrick, who are my crown
and joy and hopefully will carry the torch forward.
My parents, Chandran and Vimala, who taught me the important
things in life.
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Contents
Preface xi
Acknowledgments xiii
Foreword xv
1. Introduction 1
2. Cell signaling:Anoverview 7
2.1 Introduction 7
2.2 Modesofcellcommunication 7
2.3 Phasesincellsignaling 9
2.3.1 Reception 9
2.3.2 Transduction 13
2.4 Response 18
2.5 Mechanicalsignalingincells 20
2.5.1 Cellstructuralelementsthatareimportantinmechanicalsignaling 20
2.5.2 Mechanosensingormechanoreception 24
2.5.3 Signaltransmission 24
2.5.4 Targetactivation 25
2.5.5 Geneexpression 25
3. Cell signaling under mechanicalstimulus in specificcell types 29
3.1 Introduction 29
3.2 Forcesactingoncells 29
3.3 Modesofmechanosensing 30
3.4 Factorsaffectinggeneralcellresponse 33
3.4.1 Stressstateofthecell 33
3.4.2 Substratecharacteristics 34
3.4.3 Temporalresponseofcellstoappliedmechanicalstimulus 35
3.5 Cellmechanotransductioninmusculoskeletaltissue 37
3.5.1 Typesofcellsinbonetissue 37
3.5.2 Themechanosensoryenvironmentofbonecells 38
3.5.3 Themechanoreceptorsinbonecells 39
3.5.4 Signalingpathwaysinbonecells 40
3.5.5 Theresponseofbonecellstoappliedmechanicalstimulus 43
3.6 Cellmechanotransductionincartilage 43
3.6.1 Mechanicalenvironmentofcartilaginouscells 43
3.6.2 Mechanismsofmechanotransductioninchondrocytes 43
vii
viii Contents
3.7 Cellularmechanotransductioninpulmonarytissue 44
3.7.1 Typesofcellsinlungtissue 44
3.7.2 Mechanicalenvironmentinthelung 45
3.7.3 Mechanismsofmechanotransductioninthelung 46
3.8 Cellmechanotransductionisthecardiovascularsystem 48
3.8.1 Typesofcellsinthecardiovascularsystem 48
3.8.2 Mechanicalenvironmentforcardiovascularcells 48
3.8.3 Mechanismsofmechanotransductionincardiovascularcells 49
3.9 Cellmechanotransductioninnervetissue 52
3.9.1 Typesofcellsinthenervoussystem 52
3.9.2 Mechanicalenvironmentfornervecells 53
3.9.3 Mechanismsofmechanotransductioninthenervecells 54
4. Cell characteristics resulting from mechanicalstimulus 57
4.1 Introduction 57
4.2 Effectofmechanicalstimulionnormalcells 57
4.2.1 Typesofmechanicalstimuli 57
4.2.2 Influenceofmechanicalfactors 58
4.2.3 Effectofsubstratecharacteristics 59
4.2.4 Effectofscaffoldproperties 60
4.2.5 Mechanotransductionatthemolecularlevel 61
4.3 Effectofmechanicalstimulionstemcells 67
4.3.1 Incongruencyincellresponse 67
4.3.2 Typesofmechanicalstimuli 68
4.3.3 Stemcellresponsetomechanicalstimuli 69
4.4 Effectofmechanicalstimulioncancercells 74
4.5 Theroleofcelladhesionmoleculesinmechanosensing 80
4.6 Cellularproliferation 82
4.7 Extracellularmatrixremodeling 84
5. Tissue mechanotransduction 91
5.1 Introduction 91
5.2 Signalcharacteristics 93
5.3 Signalcontrol:Structuralandsecretoryfactors 95
5.3.1 Adherensjunctions 95
5.3.2 Gapjunctions 95
5.3.3 Secretoryfactors 96
5.4 Musculoskeletalsystem 97
5.4.1 Mechanophysiologicalenvironment 97
5.4.2 Mechanotransductioninmusculoskeletaltissue 102
Contents ix
5.5 Pulmonarysystem 104
5.5.1 Mechanophysiologicalenvironment 104
5.5.2 Mechanotransductioninpulmonarytissue 107
5.6 Cardiovascularsystem 108
5.6.1 Mechanophysiologicalenvironment 108
5.6.2 Mechanotransductionincardiovasculartissue 111
5.7 Nervoussystem 112
5.7.1 Mechanophysiologicalenvironment 112
5.7.2 Mechanotransductioninnervetissue 113
6. Mechanotherapy 117
6.1 Introduction 117
6.2 Mechanotransductionanddisease 118
6.3 Mechanotherapy:Molecularscale 124
6.4 Mechanotherapy:Tissuelevel 125
6.5 Emergingtrendsinmechanotherapy 126
6.6 Cancertherapyandmechanotransduction 127
6.7 Othertherapeuticeffectsofmechanicalstimulus 127
7. Future thrustsinthe field of mechanotransduction 129
Bibliography 133
Index 139
