Dynein-microtubule forces drive nucleokinesis and transmigration in T cells

Authors

Tagay, Y., Zhovmer, A. S., Sarkar, N., Stoop, J., Su, L., Flezsar, L., Peterman, E., Rasmussen, J. P., Cartagena-Rivera, A. X., Tsygankov, D., Tabdanov, E. D.

Abstract

Beyond the mechanical capacity of canonical actomyosin-driven amoeboid motility in permissive extracellular environments, the nucleus becomes the principal barrier to T cell migration in confining tissues. We establish the dynein-microtubule (MT) force-transmission axis as an essential mechanism for nuclear translocation during confined T cell migration and transmigration. We argue that dynein acts both as a motor and as an F-actin-anchored force-transmission element (fulcrum), sliding MTs and the MT-coupled nucleus along the cell cortex to drive nucleokinesis and productive cell displacement. Dynein is the primary driver of nucleokinesis: its inhibition arrests nucleus movement independently of myosin II activity, while F-actin dynamics remain spatiotemporally decoupled from nuclear oscillations. During transmigration, dynein and actomyosin act cooperatively and non-redundantly, and only combined inhibition abolishes nuclear passage. Computational modeling demonstrates that dynein-mediated pulling, together with volume exclusion imposed by the nucleus, is sufficient to generate self-organized nuclear oscillations. Dynein inhibition in zebrafish Langerhans cells impairs protrusion dynamics in situ, identifying the dynein-MT axis as an evolutionarily conserved mechanobiological program. Collectively, these findings identify the dynein-MT mechanical unit as a potential target for engineering T cells with enhanced solid-tumor infiltration.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 11 Jul 2026.

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