A Microtubule Mechanostat Enables Cells to Navigate Confined Environments

Cells migrating through complex 3D environments face considerable mechanical challenges. Cortical contractility must be highly coordinated to drive both cell movement and squeeze the large nucleus through confined regions. How cells protect themselves against mechanical forces and achieve nuclear transmigration in this context is largely unknown. Here, we demonstrate that cells experiencing confinement form a microtubule-dependent mechanostat in response to compressive forces. The mechanostat is an adaptive feedback mechanism whereby compressive loading of microtubules recruits CLASPs (cytoplasmic linker-associated proteins) to dynamically tune and repair the lattice. These reinforced microtubules allow the cell to withstand force and spatiotemporally organize contractility signaling pathways. Disruption of the mechanostat imbalances cortical contractility, stalling migration and ultimately resulting in catastrophic cell rupture. ### Competing Interest Statement The authors have declared no competing interest.