Tunable transport of lytic granules in Cytotoxic T Lymphocytes

Cytotoxic T Lymphocytes (CTLs) eliminate target cells by forming an immune synapse (IS) at the interface of the CTL and the target cell. The elimination is facilitated by the directed secretion of lytic granules - specialized lysosomes containing cytotoxic proteins - at the IS. Upon activation, granules are transported in two simultaneous stages: Convergence, where granules are transported by dynein motors towards the centrosome via Microtubules (MTs), and Polarization, where the centrosome translocates towards the IS carrying the granules with it. We investigate transport efficiency using a two-layer 1D model with a reflecting boundary (cell membrane) and an absorbing boundary (IS). In the model, two MTs join at the centrosome. Granules switch between the Diffusive Layer (when detached from MTs) and the Advective Layer (when attached to MTs), governed by attachment/detachment rates. We vary these rates, centrosome velocity, and granule velocity to match experimental data. With this, we address whether there exists an optimal regime in terms of granule flux to the IS. By mapping the parameter landscape, we identify which variables—attachment kinetics, motor speeds, or centrosome dynamics—most strongly influence killing efficiency, providing insight into the “knobs” that CTLs may fine-tune for optimal cytotoxic response.