ABSTRACT
T cells migrate in nearly every healthy, inflamed or diseased tissue. Such ‘all-terrain’ motility is achieved by a dynamic mechanobiological balance between amoeboid and mesenchymal-like migration modes. Here, we report that septin proteins function as a key regulator of migratory balance in T cells. We show that active septins compartmentalize the lymphocyte’s cortex into a peristaltically treadmilling ‘tube’ during avoidance response to mechanically crowding hindrances. T cell cortical peristaltism mechanically channels nucleus and cytoplasm between mechanically crowding 3D collagen fibers. Septins’ inactivation shifts T cell motility balance towards mesenchymal-like mode, characterized by distinct contact guidance and MAP4-, SEPT9-, HDAC6-mediated enhancement of microtubules and microtubule-associated dynein contractility. The non-stretchable microtubular cables secure structurally coherent cell passage through confining spaces and long-distance transmission of dynein-generated forces, which replace diminished actomyosin contractility. Thus, septins provide T cells with a structural and signaling molecular switch between actomyosin-driven amoeboid and dynein-driven mesenchymal-like migration.
GLOSSARY
Steric interactions - objects interactions by the means of their spatial collision, determined by objects’ shapes.
Steric guidance - T cell navigation within crowded 3D environments, determined by the available passages around and between steric hindrances.
Peristaltic treadmilling - locomotion mode by the means of repeated series of polarized cell cortex extension, stabilization, and retraction, accompanied by translocation of nucleus and cytoplasm via circumferential cortex contractility.
Dynein contractility - contractile forces within a system of non-stretchable, force-transmitting microtubular cables, generated by dynein motor proteins.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
One of the co-authors has detected a misspelling of his name (Xuefei, not Xufei) and inquired to fix the mistake.