TY - JOUR T1 - A Microtubule Mechanostat Enables Cells to Navigate Confined Environments JF - bioRxiv DO - 10.1101/2022.02.08.479516 SP - 2022.02.08.479516 AU - Robert J. Ju AU - Alistair D. Falconer AU - Caitlyn K.X. Tang AU - Kevin M. Dean AU - Reto P. Fiolka AU - David P. Sester AU - Max Nobis AU - Paul Timpson AU - Alexis J. Lomakin AU - Melanie D. White AU - Dietmar B. Oelz AU - Nikolas K. Haass AU - Samantha J. Stehbens Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/09/2022.02.08.479516.abstract N2 - 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 StatementThe authors have declared no competing interest. ER -