Microtubule control of migration: Coordination in confinement

Abstract

The microtubule cytoskeleton has a well-established, instrumental role in coordinating cell migration. Decades of research has focused on understanding how microtubules couple intracellular trafficking with cortical targeting and spatial organization of signaling to facilitate locomotion. Movement in physically challenging environments requires coordination of forces generated by the actin cytoskeleton to drive cell shape changes, with microtubules acting to spatially regulate contractility. Recent work has demonstrated that the mechanical properties of microtubules are adaptive to stress, leading to a new understanding of their roles in cell migration. Herein we review new developments in how microtubules sense and adapt to changes in the physical properties of their environment during migration. We frame our discussion around our current understanding of how microtubules target cell-matrix adhesions, and their role in the spatiotemporal coordination of signaling to form mechano feedback loops. We expand on how these mechanisms may influence cell morphology in confined three-dimensional settings, and the importance of locally tuning the mechanical stability of polymers in response to mechanical cues. Finally, we discuss new roles for Golgi-derived microtubules in mechanosensing, and how preferential motor use may influence polymer stability to resist the physical constraints cells experience in confined environments.