Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels
| Autor: | Wesley R. Legant, Murat Guvendiren, Sudhir Khetan, Daniel M. Cohen, Christopher S. Chen, Jason A. Burdick |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Materials science
Cellular differentiation Proteolysis macromolecular substances Cell morphology complex mixtures Article chemistry.chemical_compound Osteogenesis Hyaluronic acid medicine Humans General Materials Science Hyaluronic Acid medicine.diagnostic_test Mechanical Engineering Mesenchymal stem cell technology industry and agriculture Cell Differentiation Hydrogels Mesenchymal Stem Cells General Chemistry Condensed Matter Physics chemistry Mechanics of Materials Adipogenesis Covalent bond Self-healing hydrogels Biophysics |
| Zdroj: | Nature materials |
| ISSN: | 1476-1122 |
| Popis: | Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional (3D) encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular-traction, independent of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that either permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). In addition, switching the permissive hydrogel to a restrictive state via delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Also, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment. |
| Databáze: | OpenAIRE |
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