Hydrogels With Tunable Stress Relaxation Regulate Stem Cell Fate and Activity

Nat Mater. 2016 Mar;15(3):326-34. doi: 10.1038/nmat4489. Epub 2015 Nov 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Biomechanical Phenomena
  • Cell Culture Techniques
  • Cell Differentiation
  • Extracellular Matrix
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Hydrogels
  • Mesenchymal Stem Cells / physiology*
  • Stress, Mechanical

Substances

  • Alginates
  • Hexuronic Acids
  • Hydrogels
  • Glucuronic Acid