Cells reside within the extracellular matrix (ECM), a complex 3D mesh of proteins and other macromolecules that provide anchorage support for cells but also instruct them with relevant signals that trigger different processes, such as cell migration and (stem) cell differentiation. During this seminar, we will show examples of how different physical properties of the ECM play a key role in controlling cell behaviour, and how to recapitulate these aspects of the natural ECM by designing materials with application in cell engineering and regenerative medicine. Our examples will include viscoelastic properties and the importance of the presentation of growth factors – key signalling molecules that control cell development and hence regeneration – tethered to the ECM, and in crosstalk with integrins. In a futuristic approach, we will show how to engineer living interfaces based on bacteria that control stem cell behaviour by providing, in a temporal controlled manner, adhesive molecules and growth factors to stem cells.