Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

Living cells respond to their mechanical microenvironments during development, healing, tissue remodeling and homeostasis attainment. However, this mechanosensitivity has not yet been established definitively for cells in three-dimensional (3D) culture environments, in part because of challenges associated with providing uniform and consistent 3D environments that can deliver a large range of physiological and pathophysiological strains to cells. Here, we report microscale magnetically actuated, cell-laden hydrogels (μMACs) for investigating the strain-induced cell response in 3D cultures. μMACs provide high-throughput arrays of defined 3D cellular microenvironments that undergo reversible, relatively homogeneous deformation following non-contact actuation under external magnetic fields. We present a technique that not only enables the application of these high strains (60%) to cells but also enables simplified microscopy of these specimens under tension. We apply the technique to reveal cellular strain-threshold and saturation behaviors that are substantially different from their 2D analogs, including spreading, proliferation, and differentiation. μMACs offer insights for mechanotransduction and may also provide a view of how cells respond to the extracellular matrix in a 3D manner. Micromechanical strain is shown to play a key role in the growth and development of tissue and muscle cells in three-dimensional environments. Feng Xu and co-workers have developed an innovative medium for visualizing and influencing cell growth with biocompatible, water-based hydrogels. Using photolithography, the team fabricated a micrometre-thick, multilayer device in which cell-laden hydrogels sat above a separate hydrogel film infused with magnetic iron nanoparticles. Applying a magnetic field caused the lower hydrogel film to deform homogenously, altering the strain of the three-dimensional cell-growth region by up to 60 per cent. This method has the advantage that it does not use damaging mechanical contacts. The transparent hydrogels enable real-time microscopy imaging of fibroblast and myoblast viability and proliferation under realistic strain conditions — valuable data for artificial muscle applications and pathophysiological studies of injury healing. We report microscale magnetically actuated, cell-laden hydrogels (μMACs) for investigating the strain-induced cell response in three-dimensional (3D) microenvironments. These μMACs provide high-throughput arrays of defined 3D cellular microenvironments that undergo reversible, relatively homogeneous deformation following non-contact actuation under external magnetic fields. Such technique not only enables the application of high strains (up to 60%) to cells but also enables simplified microscopic visualization of these specimens under tension. The μMACs offer insights for mechanotransduction and may also provide a view of how cells respond to extracellular matrix in 3D.