Mechanical coupling between the actomyosin and microtubule systems during T-cell activation

Activation of T-cells leads to the formation of immune synapses (IS) with antigen-presenting cells. This requires T-cell polarization and coordination between the actomyosin and microtubule cytoskeletons. The interactions between these two cytoskeletal components during T-cell activation are not well understood. Here, we elucidate the interactions between microtubules and actin at the IS with high-resolution fluorescence microscopy. We show that microtubule growth dynamics is modulated by actin nucleators. Formin inhibition results in a moderate decrease in microtubule growth rates, which is amplified in the presence of integrin engagement. In contrast, Arp2/3 inhibition leads to an increase in microtubule growth rates. We also find that actin dynamics and actomyosin contractility play key roles in defining microtubule deformations and shape fluctuations. Interestingly, we find that nuclear mechanics modulates cytoskeletal dynamics and alters the coordination between actomyosin and microtubule cytoskeletons. Treatment with histone deacetylase inhibitor, trichostatin-A, causes nuclear softening, higher actin accumulation and disrupts centrosome polarization. Our results indicate a mechanical coupling between the actomyosin and microtubule systems during T-cell activation, that is essential for proper IS formation and maturation.