Model of T cell migration through the extracellular matrix

T cells must push their stiff nucleus through narrow passages during their migration through the extracellular matrix (ECM). This migration is aided by septin and actin filaments that assemble into a cortical ring around the nucleus, at locations where ECM collagen fibers create strong indentations of the cell (Zhovmer et al. Sci. Adv. 2024). The rings subdivide the cell into compartments with potentially different hydrostatic pressure and biochemical composition. To better understand factors governing T cell motility, we developed a 2D model representing the cell cortex and nucleus as beads connected with springs and area conservation between compartments. We assume that rings form at sites where obstacles enforce proximity between the cortex and nucleus. Assuming a predefined cell polarization and implementing blebbing at the cell front and contraction at the cell rear, we show that compartmentalization pushes the nucleus by a piston mechanism, enabling cells to move farther through a density gradient of obstacles. We quantified mean root square displacement through an ECM of randomly placed obstacles as a function of leading edge repolarization dynamics. An optimal local repolarization indicates how mechanical and signaling systems may coordinate to enhance T cell motion.