Knaus and Mundlos analyse the effects of mechanical stimuli, which are so essential for bone healing, on chromatin folding and gene regulation. They hypothesise that mechanical forces influence gene expression via re-positioning of the chromatin in the three-dimensional space of the nucleus. Alterations of the extracellular matrix composition, the fluid shear stress and other external forces might therefore modulate gene transcription during disease and tissue regeneration. Preliminary data with endothelial cells shows striking changes in cellular mechanics, nuclear lamina and extracellular matrix composition, as well as increased F-actin bundling and tubulin acetylation, resulting in increased cellular tension and nuclear deformation. Knaus and Mundlos characterise the nuclear modifications, identify lamina associated domains and perform chromosome conformation capture to characterise the nuclear three-dimensional organisation upon mechanical stimulation.