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Summary
Directed cell migration in multicellular organisms is essential to fundamental processes including embryogenesis, defense from infection, and tissue repair and regeneration. It is also key in cancer progression as metastatic cells disseminate throughout the body. Much research has focused on cells migrating on two-dimensional (2D) extracellular matrices (ECMs) because such experimental systems are easily accessible and observable. However, recent studies of cell motility in 3D environments are challenging the ubiquity and generality of 2D-based models. On page 1062 of this issue, Petrie et al. (1) propose that in a constrained 3D space, a cell can use its nucleus as a piston to polarize internal pressure and create protrusions that facilitate movement.