Hydrogels with tunable stress relaxation regulate stem cell fate and activity
Ovijit Chaudhuri,Ovijit Chaudhuri,Ovijit Chaudhuri,Luo Gu,Luo Gu,Darinka D. Klumpers,Darinka D. Klumpers,Darinka D. Klumpers,Max Darnell,Max Darnell,Sidi A. Bencherif,Sidi A. Bencherif,James C. Weaver,Nathaniel Huebsch,Hong-pyo Lee,Evi Lippens,Evi Lippens,Georg N. Duda,David J. Mooney,David J. Mooney +19 more
TLDR
It is found that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation, highlighting stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.Abstract:
Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel's initial elastic modulus, degradation, and cell-adhesion-ligand density. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.read more
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Designing hydrogels for controlled drug delivery.
Jianyu Li,David J. Mooney +1 more
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.
Journal ArticleDOI
Modeling Physiological Events in 2D vs. 3D Cell Culture.
Kayla Duval,Hannah Grover,Li-Hsin Han,Yongchao Mou,Adrian F. Pegoraro,Jeffery J. Fredberg,Zi Chen +6 more
TL;DR: 2D and 3D cell culture methods are reviewed, advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes are discussed, and directions for future research are suggested.
Journal ArticleDOI
Mechanical forces direct stem cell behaviour in development and regeneration
Kyle H. Vining,David J. Mooney +1 more
TL;DR: Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.
Journal ArticleDOI
Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores
Alberto Elosegui-Artola,Ion Andreu,Ion Andreu,Amy E. M. Beedle,Amy E. M. Beedle,Ainhoa Lezamiz,Ainhoa Lezamiz,Marina Uroz,Anita Joanna Kosmalska,Roger Oria,Jenny Z. Kechagia,Palma Rico-Lastres,Palma Rico-Lastres,Anabel-Lise Le Roux,Catherine M. Shanahan,Xavier Trepat,Daniel Navajas,Sergi Garcia-Manyes,Sergi Garcia-Manyes,Pere Roca-Cusachs +19 more
TL;DR: This work shows that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport, demonstrated for YAP but with potential general applicability in transcriptional regulation.
Journal ArticleDOI
Effects of extracellular matrix viscoelasticity on cellular behaviour.
TL;DR: The role of viscoelasticity of tissues and extracellular matrices in cell–matrix interactions and mechanotransduction and the potential utility of vis coelastic biomaterials in regenerative medicine are explored.
References
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Journal ArticleDOI
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.
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Tissue Cells Feel and Respond to the Stiffness of Their Substrate
TL;DR: An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.
Journal ArticleDOI
Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering
TL;DR: Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.
Journal ArticleDOI
Role of YAP/TAZ in mechanotransduction
Sirio Dupont,Leonardo Morsut,Mariaceleste Aragona,Elena Enzo,Stefano Giulitti,Michelangelo Cordenonsi,Francesca Zanconato,Jimmy Le Digabel,Mattia Forcato,Silvio Bicciato,Nicola Elvassore,Stefano Piccolo +11 more
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.