PT  - JOURNAL ARTICLE
AU  - Jeremy Keys
AU  - Brian C.H. Cheung
AU  - Mingming Wu
AU  - Jan Lammerding
TI  - Rear cortex contraction aids in nuclear transit during confined migration by increasing pressure in the cell posterior
AID  - 10.1101/2022.09.10.507419
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.10.507419
4099  - http://biorxiv.org/content/early/2022/09/10/2022.09.10.507419.short
4100  - http://biorxiv.org/content/early/2022/09/10/2022.09.10.507419.full
AB  - As cells migrate through biological tissues, they must frequently squeeze through micron-sized constrictions in the form of interstitial pores between extracellular matrix fibers and/or other cells. Although it is now well recognized that such confined migration is limited by the nucleus, which is the largest and stiffest organelle, it remains incompletely understood how cells apply sufficient force to move their nucleus through small constrictions. Here, we report a novel mechanism by which contraction of the cell rear cortex pushes the nucleus forward to mediate nuclear transit through constrictions. Laser ablation of the rear cortex reveals that pushing forces behind the nucleus are the result of increased intracellular pressure in the rear compartment of the cell. The pushing forces behind the nucleus depend on accumulation of actomyosin in the rear cortex and require Rho-kinase (ROCK) activity. Collectively, our results suggest a novel mechanism by which cells generate elevated, intracellular pressure in the posterior compartment to facilitate nuclear transit through 3D constrictions. This mechanism may supplement or even substitute for other mechanisms supporting nuclear transit, ensuring robust cell migrations in confined 3D environments.Competing Interest StatementThe authors declare no competing interests. Jan Lammerding has received consulting fees from BridgeBio on unrelated projects.