Engineering and Physical Approaches to Cancer

Preface
Contents
Mechanobiology of Collective Cell Migration in 3D Microenvironments
1 Introduction
2 Collective Cell Migration and Leader-Follower Interactions
3 Analyzing Collective Migration Using Phase Transitions and Order Parameters
4 Metabolic Heterogeneity and Mechanobiological Phenotype
5 The Extracellular Matrix and Engineered Biomaterials
6 Precision Measurement of Cell and ECM Mechanics
7 Epithelial-Mesenchymal Plasticity and Collective Cell Migration
8 Perspective and Future Directions
References
Collective Cellular Phase Transitions in Cancer
1 Introduction
2 Cell Jamming: From Sand to Cells
2.1 Hallmarks of Collective Cellular Phase Transitions
2.1.1 Arrest of Motion
2.1.2 Changes in Bulk Rheology
2.1.3 Dynamic Heterogeneity
2.1.4 Structural Changes
2.2 Understanding Collective Cell Dynamics Through Phase Transitions
2.2.1 The Complex Roles of Cell Density, Division, and Maturation
2.2.2 Phase Transitions at Boundaries
2.2.3 Density-Independent Phase Transitions
2.2.4 Local Coordination and Flocking
3 Phase Transitions in Cancer
3.1 Tumor Invasion: Force Balance
3.2 Cell Jamming as Cell Phenotype Changes
3.3 What Is the Role of the Jammed State in Cancer?
4 Perspective for the Future
References
Biophysical and Biochemical Mechanisms Underlying Collective Cell Migration in Cancer Metastasis
1 Introduction: Collective Cell Migration
2 Factors Influencing Collective Cell Migration
2.1 Direct Cell-Cell Mechanical Interactions
2.2 Direct Cell-Cell Biochemical Interactions
2.3 Indirect Cell-Cell Interactions via the Environment
2.4 Collective Cell Migration Beyond Cell-Cell Interactions
3 Collective Cell Migration in Cancer
4 Discrete, Continuum, and Hybrid Models
4.1 Isotropic Active Particles Model
4.2 Deformable Particle Model
4.3 Subcellular Element Models
4.4 Active Network Models: Vertex/Voronoi Models
4.4.1 Key Insights: Transitions in Epithelia
4.5 Cellular Automata
4.5.1 BioLGCA
4.5.2 Cellular Potts Model
4.6 Phase-Field Model
4.7 Finite Element Immersed Boundary Models
4.8 Hydrodynamic Models
4.9 Simulation Platforms
4.10 Machine Learning-Based Techniques
5 Biochemical Models
5.1 ODE-Based Models
5.2 Boolean Models
6 Conclusions and Future Directions
References
Hallmarks of an Aging and Malignant Tumor Microenvironment and the Rise of Resilient Cell Subpopulations
1 Introduction: Hallmark Physical and Molecular Cancer Traits
2 Tumor Microenvironment
2.1 Overview of Cell Types in the Tumor Microenvironment
2.2 Tumor-Infiltrating Immune Cells
2.3 Tumor-Associated Fibroblasts
2.4 Tumor-Associated ECM
2.5 Tumor Angiogenesis
2.6 Tumor-Secreted Soluble Factors
2.7 Tumor Exosomes
3 Intratumor Heterogeneity
3.1 Heterogeneity in Tumor Mechanics
3.2 Heterogeneity in Cell Phenotype
3.3 Senescent Stromal Cells
3.4 Polyploid Giant Cancer Cells
4 Concluding Remarks
References
Physical Regulations of Cell Interactions and Metabolism in Tumor Microenvironments
1 Introduction
2 Effect of Stiffness on Tumor–Stromal Interaction and Metabolism in the TME
3 Effect of Solid Stress on Tumor–Stromal Interaction and Metabolism in the TME
4 Effect of Shear Stress on Tumor–Stromal Interaction and Metabolism in the TME
5 Conclusion
References
Biophysical Regulation of TGFβ Signaling in the Tumor Microenvironment
1 Introduction
2 Dynamic Changes in Tumor Mechanics Accompany Cancer Progression
3 TGFβ Signaling in Cancer
3.1 Cancer-Associated Fibroblasts Respond to and Mediate TGFβ Signaling
3.2 TGFβ Induces Epithelial–Mesenchymal Transition
3.3 TGFβ Induces Genomic Instability
4 Mechanical Activation of TGFβ
5 Mechanical Regulation of TGFβ-Induced Signaling Cascades
5.1 EMT-Associated Transcription Factors
5.2 RhoA/ROCK
5.3 Integrin-Linked Kinase
5.4 Myocardin-Related Transcription Factors
5.5 Hippo Pathway
6 Effect of Matrix Dimension on TGFβ-Induced EMT
7 Targeting TGFβ-Associated Mechanoresponsive Pathways for Treatment of Cancer
8 Summary
References
Bioengineering and Bioinformatic Approaches to Study Extracellular Matrix Remodeling and Cancer-Macrophage Crosstalk in the Breast Tumor Microenvironment
1 Introduction
2 Macrophage Recruitment in Breast Tumors
3 Mechanisms of Macrophage Migration in 3D Environments
4 Matrix Remodeling and Cancer Cell–Macrophage Dynamics
4.1 Tumor ECM Composition
4.2 Cell–Matrix Adhesion
4.3 Matrix Crosslinking and Fiber Alignment
4.4 Matrix Degradation and Formation of Microtracks That Promote Cancer Cell and Macrophage Migration
5 Bioengineering Approaches to Dissect Extracellular Matrix Complexity and Quantify Cancer–Macrophage Dynamics
5.1 Engineering the Extracellular Matrix Structure
5.2 Quantification of Matrix Remodeling
6 Bioinformatic Analysis of ECM- and Macrophage-Specific Gene Signatures
6.1 Extracellular Matrix Gene Signatures
6.2 TAM-Specific Gene Expression Signatures
7 Summary and Future Perspectives
References
Engineering Approaches in Ovarian Cancer Cell Culture
1 Introduction
2 OC Progression
2.1 Initiation
2.2 Dissemination
2.3 OC Metastatic Microenvironment
2.4 Tumor Expansion After Therapy
3 In Vitro Modeling of OC: What to Consider Before Starting the Project
4 In Vitro Culture Models of OC
4.1 Two-Dimensional (2D) Tissue Cultures
4.2 Spheroid Cultures
4.3 Organotypic OC Cultures
4.4 Organoid Cultures of the Fallopian Tube and OC Cells
4.5 OC Cultures with Natural and Synthetic Polymers
4.6 Integration of OC Tissue Culture with Microfluidics
5 Concluding Remarks
References
Biophysical Properties and Isolation of Circulating Tumor Cells
1 Introduction
2 Physical Environment of CTCs and Engineering Approaches for Research
2.1 Introduction
2.2 CTCs Experience Fluid Shear Stress
2.3 CTCs Experience Numerous Collisions
2.4 CTCs Experience Traction Forces
2.5 CTCs Experience Compressive Forces
3 CTC Detection and Isolation Methods
3.1 Introduction
3.2 Positive Selection Approach to CTC Isolation
3.3 Negative Selection Approach to CTC Isolation
3.4 Density-Gradient-Based CTC Isolation
3.5 Size-/Deformability-Based CTC Isolation
3.6 Acoustofluidic-Based CTC Isolation
3.7 Dielectrophoresis-Based CTC Isolation
3.8 Caveats and Future Directions
4 Conclusions
References
In Vitro and In Vivo Host Models of Metastasis
1 Rodent Models
2 Fish Models
3 Microfluidic and In Vitro Systems
4 Complementary Investigations Using In Vitro and In Vivo Models
5 Multiple Integrated Models
6 Summary
References
Physical Sciences in Cancer: Recent Advances and Insights at the Interface
1 Introduction
2 Mathematical and Computational Modeling of Cancer
2.1 Modeling the Roles of Tumor Microenvironment
2.2 Modeling Cancer Cell Migration
2.3 Modeling Cancer Evolution and Response to Therapy
2.4 Limitations of Computational and Mathematical Modeling
3 Microfluidics and Hydrogels in Cancer Studies
4 Physical Cues in Cancer Biology
4.1 Effect of Tumor Microenvironment Stiffness on Cancer Progression
4.2 Solid Stress and Tumor Progression
4.3 T-Cells and Mechanical Forces
4.4 Physical Cues on Cancer Cell Nucleus and Genome
4.4.1 Nucleus and the Nuclear Envelope
4.4.2 Nuclear Lamina
4.4.3 Effect of Constriction on DNA Damage
5 Summary and Future Direction
References
Index