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Magnetic Nanocomposite Hydrogel with Tunable Stiffness for Probing Cellular Responses to Matrix Stiffening

As cells have the capacity to respond to their mechanical environment, cellular morphology and function can be regulated by the stiffness of extracellular matrix. Moreover, biological processes are accompanied by dynamic changes in matrix stiffness. Herein, we developed a novel stiffening cell culture platform based on magnetic nanocomposite hydrogels with tunable stiffness under the application of magnetic field. This platform provided a wide tunable range of stiffness (~0.3-20 kPa), which covered most of human tissue elasticity (such as brain, fat, and muscle), and a maximum increase of stiffness and rate of stiffness increment of over 17 kPa and 1500%, respectively, without adversely affecting cell viability. Overall, the increased magnetic interactions between magnetic nanoparticles reduced the pore size of hydrogels and enhanced the hydrogel stiffness, thereby facilitating the adhesion and spreading of stem cells, which was attributed to the F-actin assembly and vinculin recruitment. Such stiffening platform not only provided valuable insights into the role of tunable stiffness as a morphological regulator of stem cells, but also allowed for better simulations of biomechanical environments in vivo to investigate dynamic biological processes.