The elasticity of biological tissues [usually expressed in pascals (Pa)] has an important role in determining processes such as cellular adhesion and differentiation. For example, mesenchymal stem cells express neurogenic markers when cultured on a 1-kPa substrate resembling brain tissue, but express osteogenic markers when cultured on a 100-kPa substrate resembling nascent bone. Now, Dominique Vautier and colleagues (p. 29) address how substrate elasticity influences nuclear structure and function in a model system involving PtK2 cells and nanostructured films with regulatable stiffness. They show that increasing substrate stiffness causes increased cell adhesion, and that activation of focal adhesion (FA) kinase – a key factor in FA-contact signalling – occurs selectively on substrates with defined elasticity. In line with findings that FA dynamics and the cell cycle are linked, the authors also show that inhibition of FA assembly correlates with inhibition of DNA replication when cells are cultured on substrates with elasticity <50 kPa. Furthermore, they propose that the small GTPase Rac1 links substrate-induced changes in FAs, the formation of actin stress fibres and DNA replication. Substrates with elasticity >50 kPa also cause histone H3 hyperacetylation, which permits active transcription. Finally, they show that substrate-induced changes in transcription can occur independently of the actin cytoskeleton, indicating that mechanically transduced signals can influence nuclear activities both directly and via morphological changes.