Rädler Group: new publication on cell migration
9 Sept 2024
'Nuclear deformation and dynamics of migrating cells in 3D confinement reveal adaptation of pulling and pushing forces' has been published in Science Advances
9 Sept 2024
'Nuclear deformation and dynamics of migrating cells in 3D confinement reveal adaptation of pulling and pushing forces' has been published in Science Advances
Stefan Stöberl, Johannes Flommersfeld, Maximilian M. Kreft, Martin Benoit, Chase P. Broedersz, Joachim O. Rädler
Sci. Adv. 10, eadm9195 (2024)
Eukaryotic cells show an astounding ability to remodel their shape and cytoskeleton, to migrate through pores and constrictions smaller than their nuclear diameter. However, the relation of nuclear deformation and migration dynamics in confinement remains unclear. Here, we study the mechanics and dynamics of mesenchymal cancer cell nuclei transitioning through 3D compliant hydrogel channels. We find a biphasic dependence of migration speed and transition frequency on channel width, peaking at widths comparable to the nuclear diameter. Employing confocal imaging and hydrogel bead displacement, we determine nuclear deformations and corresponding forces during confined migration. The nucleus deforms reversibly with a reduction in volume during confinement. With decreasing channel width, the nuclear shape during transmigration changes biphasically concomitant with the transitioning dynamics. Our proposed physical model explains the observed nuclear shapes and transitioning dynamics in terms of the cytoskeletal force-generation adapting from purely pulling-based to a combined pulling- and pushing-based mechanism with increasing nuclear confinement.