Mitosis sets nuclear homeostasis of cancer cells under confinement

Abstract

During their life, mammalian cells are subjected to numerous mechanical constraints, especially in pathological contexts such as cancer. Most studies on cell confinement focus on short periods, and little is still known about cell adaptation to prolonged squeezing, over several cell divisions. Using a hydrogel-based confinement system, we reveal the unsuspected role of mitosis in long-term adaptation to prolonged uniaxial confinement, in a contractility-dependent manner. To adapt to the level of confinement and to alleviate the imposed mechanical stress, nuclei are reaching a new homeostatic state following the first confined cell division: cells down-regulate their nuclear volume, together with a reset of their nuclear envelope folding. A simple geometric model suggests that this new nuclear volume is triggered by the apparent surface of the nuclear envelope.Our findings have important implications for the fundamental understanding of nuclear regulation under mechanical constraints and are critical to better comprehend cancer cells plasticity.