Mechanobiology: From Molecular Sensing to Disease

Cover
Mechanobiology: From
Molecular Sensing to Disease
Copyright
Dedication
List of Contributors
Preface: Mechanobiology, why not?
	History of Mechanobiology
	Mechanobiology Across Length Scales
	Why not Mechanobiology?
	Overview
	References
Section I: Mechanobiological Basis of Diseases
1.1. Osteocyte Mechanobiology in Aging and Disease
	1. Introduction
	2. Mechanical Loading Effects on Bone: Mechanotransduction
	3. Evidence for Osteocyte-Directed Skeletal Responses
	4. Osteocytes, Mechanotransduction, and Aging
		4.1 Osteocyte Number
		4.2 Changes in Osteocyte Microenvironment
		4.3 Cell-Autonomous Alteration of Osteocyte Function
	5. Osteocytes and Disease
		5.1 Cancer
		5.2 Vascular Health
	6. Conclusions and Future Directions
	References
1.2. Cardiovascular Mechanics and Disease
	1. Introduction
	2. Cardiovascular Hemodynamics
		2.1 Overview
		2.2 Fluid Shear Stress
		2.3 Reynolds Stresses
		2.4 Cyclic Stretch
	3. Bioreactors for Cardiovascular Mechanobiological Studies
		3.1 Parallel Plate Devices
		3.2 Cone-and-Plate Bioreactors
		3.3 Stretch Bioreactors
	4. Heart Valve Mechanobiology
		4.1 Valvular Anatomy, Function, and Structure
			4.1.1 Aortic valve
			4.1.2 Mitral valve
		4.2 Valvular Hemodynamics
			4.2.1 Aortic valve
			4.2.2 Mitral valve
		4.3 Valvular Disease
			4.3.1 Calcific aortic valve disease
			4.3.2 Myxomatous valve disease
		4.4 Valvular Response to Hemodynamic Stresses
			4.4.1 Fluid shear stress mechanotransduction
			4.4.2 Tensile stress mechanotransduction
	5. Blood Vessel Mechanobiology
		5.1 Blood Vessel Anatomy, Function, and Structure
		5.2 Vascular Hemodynamics
		5.3 Vascular Disease
			5.3.1 Atherosclerosis
			5.3.2 Aneurysm
		5.4 Vascular Response to Hemodynamic Stresses
			5.4.1 Fluid shear stress mechanotransduction
			5.4.2 Tensile stress mechanotransduction
	6. From Bench to Bedside: Research Needs and Future Directions
	7. Conclusion
	References
1.3. Mechanobiology of the Optic Nerve Head in Primary Open-Angle Glaucoma
	1. Introduction
	2. Structure and Function
	3. Mechanics of the Optic Nerve Head in Glaucoma
		3.1 Intraocular Pressure and Lamina Cribrosa Remodeling
		3.2 Chronic Morphologic Changes of the Lamina Cribrosa
		3.3 Deformation and Displacement of the Optic Nerve Head in Response to Acute Intraocular Pressure Elevation
		3.4 Stiffness of the Peripapillary Sclera and Lamina Cribrosa
		3.5 Summary
	4. Mechanobiology of the Optic Nerve Head in Glaucoma
		4.1 Transforming Growth Factor β Signaling Pathway
		4.2 Proteases
		4.3 Hypoxia and Oxidative Stress
		4.4 Mechanical Stretch
		4.5 Summary
	5. Future Perspective
	References
1.4. The Role of Mechanobiology in Cancer Metastasis
	1. Introduction
	2. Mechanical Cues in the Bone Microenvironment
		2.1 Overview
		2.2 Bone Marrow Mechanics and Relevance to Metastatic Bone Cancer
			2.2.1 Interstitial fluid flow
			2.2.2 Tissue strain
			2.2.3 Extracellular matrix stiffness
			2.2.4 Hydraulic pressure
	3. Possible Mechanisms of Cancer Cell Mechanosensing of Bone Cues
		3.1 Overview
		3.2 Cell Surface/Plasma Membrane Structures
			3.2.1 Extracellular matrix linkers to actin cytoskeleton
				3.2.1.1 Integrins and focal adhesions
				3.2.1.1 Integrins and focal adhesions
				3.2.1.2 Ion channels
				3.2.1.2 Ion channels
				3.2.1.3 Cadherins
				3.2.1.3 Cadherins
			3.2.2 Other receptors/channels
		3.3 Cytoskeleton
		3.4 Nucleus
	4. Future Considerations
	References
Section II: Cellular Basis of Mechanobiology
2.1. Cells as Functional Load Sensors and Drivers of Adaptation
	1. Cells as Load-Bearing Structures
	2. Cell Membrane
		2.1 Ion Channels
		2.2 Primary Cilia
		2.3 Focal Adhesions
	3. Cytoskeleton
	4. Nucleus
		4.1 Nuclear Envelope
		4.2 Nucleoskeleton
			4.2.1 Nuclear actin and microtubules
			4.2.2 Lamin A/C
			4.2.3 Lamin B
		4.3 Chromatin
	5. Summary
	References
2.2. Primary Cilia Mechanobiology
	1. Introduction
	2. The Primary Cilium
		2.1 Structure
		2.2 Function
		2.3 Ciliopathies
	3. Primary Ciliary Mechanobiology and Mechanotransduction
		3.1 Urinary System
			3.1.1 Kidney
		3.2 Circulatory System
			3.2.1 Endothelium
		3.3 Musculoskeletal System
			3.3.1 Cartilage
			3.3.2 Bone
	4. Mechanics of Primary Cilium Biology
	5. Discussion and Future Directions
	References
2.3. In Vivo Models of Muscle Stimulation and Mechanical Loading in Bone Mechanobiology
	1. Background
	2. Bone Homeostasis, Structure, Physiology, and Basic Biomechanics
	3. Mechanical Properties and Characterization of Biological Tissues
	4. Musculoskeletal Tissue Response to Dynamic Mechanical Signals
	5. Bone Tissue Adaptation Response to High-Rate, but Low-Intensity, Mechanical Stimulation
	6. Functional Disuse-Induced Bone Loss and Muscle Atrophy
	7. Frequency-Dependent Marrow Pressure and Bone Strain Generated by Muscle Stimulation
	8. Dynamic Muscle-Stimulation-Induced Attenuation of Bone Loss
	9. Cellular and Molecular Pathways of Bone in Response to Mechanical Loading
		9.1 Basic Multicellular Units
	10. Mechanical Signal-Induced Marrow Stem Cell Elevation and Adipose Cell Suppression
	11. Osteocytes and Their Response to Mechanical Signals Coupled With Wnt Signaling
		11.1 The Role of LRP5 in Bone Response to Mechanical Loading
		11.2 MicroRNAs and Their Role in Mechanotransduction in Tissue
	12. Mechanotransductive Implications in Bone Tissue Engineering
	13. Discussion
	References
Section III: Experimental Methods
3.1. Mechanobiology in Soft Tissue Engineering
	1. Introduction
	2. Cartilage
		2.1 Cartilage Mechanobiology Review
		2.2 Engineering Cartilage
			2.2.1 Scaffold-based
			2.2.2 Scaffold-free
		2.3 Future Work
		2.4 Conclusion
	3. Tendon and Ligament
		3.1 Tendon and Ligament Mechanobiology Review
		3.2 Engineering Tendon and Ligament
			3.2.1 Scaffold-based
			3.2.2 Scaffold-free
		3.3 Future Work
		3.4 Conclusion
	4. Skeletal Muscle
		4.1 Skeletal Muscle Mechanobiology Review
		4.2 Engineering Skeletal Muscle
			4.2.1 Scaffold-based methods
			4.2.2 Scaffold-free methods
			4.2.3 Measuring force production
		4.3 Future Work
		4.4 Conclusion
	5. Conclusion
	References
3.2. Intracellular Force Measurements in Live Cells With Förster Resonance Energy Transfer–Based Molecular Tension Sensors
	1. Piconewton Forces Govern Cellular Biological Processes
	2. Principle of Förster Resonance Energy Transfer Based Molecular Tension Sensors
		2.1 A Genetically Encoded Tension Sensor Unit
		2.2 Principle of Förster Resonance Energy Transfer to Force
		2.3 Förster Resonance Energy Transfer Measurements
			2.3.1 Lifetime-based Förster resonance energy transfer
			2.3.2 Intensity-based Förster resonance energy transfer
	3. Intracellular Force Sensing With Molecular Tension Sensors
		3.1 Protein of Interest and Related Tension Sensors
		3.2 Mechanics of Focal Adhesion: Force Sensing and Cell Migration
		3.3 Force Propagation in the Cytoskeleton
		3.4 Force Transmission in Cell-Cell Junctions
	4. Perspectives
	References
Section IV: Computational Simulations in Mechanobiology
4.1. Multiscale Models Coupling Chemical Signaling and Mechanical Properties for Studying Tissue Growth
	1. Introduction
	2. Biochemical Signals Regulate Tissue Growth
	3. Mechanical Signaling Regulating Tissue Growth
	4. Modeling Dynamics of Biochemical Signals in Tissues
		4.1 Continuum Models of Biochemical Signaling in Growing Tissue Domains
		4.2 Discrete Stochastic Models of Biochemical Signaling in Tissues
	5. Modeling Biomechanical Properties of Epithelial Tissue
		5.1 Continuum Models of Tissue Mechanics
		5.2 Discrete Models of Tissue Mechanics
			5.2.1 Cellular Potts models
			5.2.2 Vertex-based models
			5.2.3 Subcellular element models
	6. Coupled Cell Signaling and Mechanical Models to Investigate Epithelial Morphogenesis
	7. Case Study: Hybrid BioMechanochemical Models of the Drosophila Wing Disc
	8. Summary and Discussion of Future Directions
	References
4.2. Computational Morphogenesis of Embryonic Bone Development: Past, Present, and Future
	1. Introduction
	2. Reaction-Diffusion Systems
	3. Morphogenic Reaction-Diffusion Systems
		3.1 Turing Patterns
		3.2 Common Morphogenic Reaction-Diffusion Systems
			3.2.1 Activator-substrate models
			3.2.2 Activator-inhibitor models
	4. Spatiotemporal Factors Affecting Patterning
		4.1 Mesh Dependency and Initial Molar Concentration Sensitivity
		4.2 Domain Geometry
		4.3 Nonrandom Initial Concentration Perturbations
	5. A Model for Cranial Vault Growth
	6. Simulating Cranial Vault Growth With Imbedded Mechanical Strain
	7. Advancements in Postnatal Cranial Vault Modeling
	8. Future Work and Conclusion
	Appendix A
	Appendix B
	References
5. Future Prospects and Challenges
	1. Introduction
	2. Cell and Cytoskeletal Mechanics
	3. Gene Editing
	4. Genetically Modified Organisms
	5. In Vivo Loading
	6. Three-Dimensional Tissue Culture and Organs-on-a-Chip
	7. Omics
	8. Imaging and Image Analysis
	9. Computational Models
	10. Data Mining, Artificial Intelligence, and Bioinformatics
	11. Summary
	References
Glossary
Index
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	Z
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