DNA folding affects how genes are turned on and off. Despite wide-spread acceptance that this folding is dynamic, little is known about how processes that change cell shape (e.g. migration across membranes) affect genome organisation and cell programming. We hypothesise that changes to cell shape during migration across membranes result in stable changes to the genome organisation that affect how the genes are turned on or off. We will use a novel interdisciplinary approach to explore how cell migration affects cell programming. Our results will form the basis for a unifying theory for cell activation that includes DNA folding, epigenetics, and gene regulation. Our work is especially relevant for understanding how immune system and cancer cells are activated when they move across membranes. It is also important for musculoskeletal and vascular cells that exhibit changes in elasticity that are associated with the onset and development of chronic diseases.