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 biological behaviors can be regulated by the stiffness of extracellular matrix. Moreover, biological processes are dynamic and accompanied by matrix stiffening. Herein, we developed a stiffening cell culture platform based on polyacrylamide-Fe₃O₄ magnetic nanocomposite hydrogel with tunable stiffness under the application of magnetic field. This platform provided a wide range of tunable stiffness (∼0.3-20 kPa) covering most of human tissue elasticity with a high biocompatibility. Overall, the increased magnetic interactions between magnetic nanoparticles reduced the pore size of the hydrogel 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 cell culture platform provides dynamic mechanical environments for probing the cellular response to matrix stiffening, and benefits studies of dynamic biological processes. STATEMENT OF SIGNIFICANCE: Cellular biological behaviors can be regulated by the stiffness of extracellular matrix. Moreover, biological processes are dynamic and accompanied by matrix stiffening. Herein, we developed a stiffening cell culture platform based on polyacrylamide/Fe₃O₄ magnetic nanocomposite hydrogels with a wide tunable range of stiffness under the application of magnetic field, without adversely affecting cellular behaviors. Such matrix stiffening caused by enhanced magnetic interaction between magnetic nanoparticles under the application of the magnetic field could induce the morphological variations of stem cells cultured on the hydrogels. Overall, our stiffening cell culture platform can be used not only to probe the cellular response to matrix stiffening but also to benefit various biomedical studies.