Engineered biomaterials are increasingly used to expand and differentiate stem cells for technological and therapeutic applications. A major open question in the field is how the mechanical properties of material scaffolds regulate stem cell differentiation, especially in complex 3D geometries like those found in tissue. In a collaborative study published in Science Advances, the labs of Sanjay Kumar and David Schaffer have discovered a 3D-specific molecular mechanism through which mechanical inputs act through the transcription factor Egr1 to determine how efficiently neural stem cells turn into neurons.