Cell migration is essential for tissue development, homeostasis, tumor progression, including the responses to wounds and inflammation. Cell interactions with their microenvironment affect many cellular functions such as spreading, migration and even differentiation. These interactions can be studied by incorporating micro- and nanotechnology-related tools. The design of substrates based on these technologies offers new possibilities to probe the cellular responses to changes in their physical environment. The investigations of the physical interactions of cells and their surrounding matrix can be carried out in well-defined and near physiological conditions. In tissues, cells encounter confined environments and narrow spaces that could favor or prevent migration. In the DURACELL ERC project, we are studying the impact of substrate stiffness on cell migration. We propose to develop and use microfabricated substrates to control substrate confinement and topography and thus analyze cellular responses. Such elastomeric substrates are designed that contain ordered micron-sized pillars allowing cells to transmigrate through versatile confined spaces. The development of accurate methods to study cellular transmigration is important to answer fundamental biological processes and for cell-based therapy and drug screening. The well-accepted methods for transmigration assays including Boyden chambers, microfluidic devices present important limitations including spatial and temporal resolutions, limited variability and control of porosity composition and geometry. To overcome these limitations, the goal of TRANSCELL is to develop in-plane micropillar substrates whose geometry can be easily tuned to control and analyze cell transmigration, cell sorting and ultimately genetic expression profiles. We anticipate that the versatility of this method will offer new opportunities for fundamental research in cell biology, but also in cell therapies and drug screening.