Matrix elasticity directs stem cell lineage specification.
TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
About: This article is published in Cell.The article was published on 2006-08-25 and is currently open access. It has received 12204 citations till now. The article focuses on the topics: Mesenchymal stem cell differentiation & Stem cell fate determination.
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TL;DR: YAP/TAZ are identified as sensors and mediators of mechanical cues instructed by the cellular microenvironment and are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry.
Abstract: Cells perceive their microenvironment not only through soluble signals but also through physical and mechanical cues, such as extracellular matrix (ECM) stiffness or confined adhesiveness. By mechanotransduction systems, cells translate these stimuli into biochemical signals controlling multiple aspects of cell behaviour, including growth, differentiation and cancer malignant progression, but how rigidity mechanosensing is ultimately linked to activity of nuclear transcription factors remains poorly understood. Here we report the identification of the Yorkie-homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1) as nuclear relays of mechanical signals exerted by ECM rigidity and cell shape. This regulation requires Rho GTPase activity and tension of the actomyosin cytoskeleton, but is independent of the Hippo/LATS cascade. Crucially, YAP/TAZ are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry; conversely, expression of activated YAP overrules physical constraints in dictating cell behaviour. These findings identify YAP/TAZ as sensors and mediators of mechanical cues instructed by the cellular microenvironment.
4,120Â citations
TL;DR: Reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence, and data show how collagenCrosslinking can modulate tissue fibrosis and stiffness to force focal adhesion, growth factor signaling and breast malignancies.
3,396Â citations
TL;DR: The extracellular matrix and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases and these properties need to be incorporated into considerations of the functions of the ECM.
Abstract: The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.
2,858Â citations
TL;DR: The functional requirements, and types, of materials used in developing state of the art of scaffolds for tissue engineering applications are described and where future research and direction is required are described.
2,648Â citations
TL;DR: This Review discusses how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation, and collects experimental release data from the literature and presents quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
Abstract: Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
2,457Â citations
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10 Nov 2008
TL;DR: In this article, the authors present a model to estimate the effect of stress and stress in one-dimensional Kinematics, and apply it to a two-dimensional elasticity problem.
Abstract: Introduction A Motivating Example: Remodeling an Underwater Structure Newton's Laws: The First Principles of Mechanics Equilibrium Definition of a Continuum Some Mathematical Basics: Scalars and Vectors Problem-solving Examples Strain and Stress in One Dimension Kinematics: Strain The Method of Sections and Stress Stress-Strain Relationships Limiting Behavior Equilibrium Stress in Axially Loaded Bars Deformation of Axially Loaded Bars Equilibrium of an Axially Loaded Bar Statically Indeterminate Bars Thermal Effects Saint-Venant's Principle and Stress Concentrations Strain Energy in One Dimension Properties of Engineering Materials A Road Map for Strength of Materials Examples Case Study 1: Collapse of the Kansas City Hyatt Regency Walkways Strain and Stress in Higher Dimensions Poisson's Ratio The Strain Tensor The Stress Tensor Generalized Hooke's Law Equilibrium Formulating Two-Dimensional Elasticity Problems Examples Applying Strain and Stress in Multiple Dimensions Torsion Pressure Vessels Transformation of Stress and Strain Failure Prediction Criteria Examples Case Study 2: Pressure Vessels Why Pressure Vessels Are Spheres and Cylinders? Why Do Pressure Vessels Fail? Beams Calculation of Reactions Method of Sections: Axial Force, Shear, Bending Moment Shear and Bending Moment Diagrams Integration Methods for Shear and Bending Moment Normal Stresses in Beams and Geometric Properties of Sections Shear Stresses in Beams Examples Case Study 3: Physiological Levers and Repairs The Forearm Is Connected to the Elbow Joint Fixing an Intertrochanteric Fracture Beam Deflections Governing Equation Boundary Conditions Beam Deflections by Integration and by Superposition Discontinuity Functions Beams with Non-Constant Cross-Section Statically Indeterminate Beams Beams with Elastic Supports Strain Energy for Bent Beams Deflections by Castigliano's Second Theorem Examples Case Study 4: Truss-Braced Airplane Wings Modeling and Analysis What Does Our Model Tell Us? Conclusions Instability: Column Buckling Euler's Formula Effect of Eccentricity Examples Case Study 5: Hartford Civic Arena Connecting Solid and Fluid Mechanics Pressure Viscosity Surface Tension Governing Laws Motion and Deformation of Fluids Examples Case Study 6: Mechanics of Biomaterials Nonlinearity Composite Materials Viscoelasticity Case Study 7: Engineered Composite Materials Concrete Plastics Ceramics Fluid Statics Local Pressure Force due to Pressure Fluids at Rest Forces on Submerged Surfaces Buoyancy Examples Case Study 8: St. Francis Dam Fluid Dynamics: Governing Equations Description of Fluid Motion Equations of Fluid Motion Integral Equations of Motion Differential Equations of Motion Bernoulli Equation Examples Case Study 9: China's Three Gorges Dam Fluid Dynamics: Applications How Do We Classify Fluid Flows? What Is Going on Inside Pipes? Why Can an Airplane Fly? Why Does a Curveball Curve? Case Study 10: Living with Water, and the Role of Technological Culture Solid Dynamics: Governing Equations Continuity, or Mass Conservation Newton's Second Law, or Momentum Conservation Constitutive Laws: Elasticity References Appendix A: Second Moments of Area Appendix B: A Quick Look at the del Operator Appendix C: Property Tables Appendix D: All the Equations Index
12Â citations