FIGURE 1:

A model for T-cell attack with dynein molecules mobile in the synaptic membrane. (A) Cytoskeletal remodeling during the IS formation of a T-cell. The chemotactic cell moves toward the APC with a leading edge of actin (yellow), its centrosome (red) is behind the nucleus (blue), and the MTs (black) reach around in the cell. Upon encountering the APC, actin spreads to form a dense ring, and the centrosome translocates toward the IS. A MT bundle forms perpendicular to the synapse and resembles a stalk. (B) Model for dynein during centrosome translocation in T-cells. Dynein molecules are mobile in the membrane, with lateral mobility that is parameterized with a drag coefficient. When bound to a MT and encountering the actin-rich boundary, a dynein molecule stalls and detaches from the MT filament. (C) The three phases of our computational T-cell model. The centrosome is not shown, for clarity. The MT-bounding volume is shown in gray, the nucleus in blue, and the centrosome-confinement space in red. In phase II, the MT-bounding volume changes and the IS is introduced with the dynein-confining synaptic membrane (purple). In phase III, the centrosome is released from the confinement space and dynein molecules (green) are added to the synaptic membrane. (D) Snapshots of the computational model at initialization (upper) and in phase II (lower). The centrosome is shown in red and MTs are shown in black. The different colors of the arrowheads at the MT tips indicate the dynamic state of the MT: stalled in red and growing in yellow. (E) Snapshots at different time points of phase III of our computational simulation. In this run, the centrosome is translocated within 96 s.