Numerical simulations indicating the impact of inter-filament cooperativity for the initiation of cofilin clusters on the fragmentation of two-filament bundles. Fraction of intact single filaments or two-filament bundles over time (n = 100 simulated two-filament bundles for each condition) upon exposure to cofilin. The reference initiation rate of cofilin clusters is the one on single filaments (blue curve, k_init,SF). On bundles, the initiation rate of the first cofilin cluster is either the one observed experimentally for fascin-induced two-filament bundles (orange and red curves, 1/6 k_init,SF) or similar to the one measured on single actin filaments (green curve, k_init,SF). The initiation rate of a second cofilin cluster, i.e., on a filament in the region facing a first cofilin cluster on the other filament, either results from interfilament cooperativity imposed by fascin bundling (see main text) (orange curve, 8 × k_init,SF) or not (red curve, 1/6 k_init,SF, and green curve, k_init,SF). Experimental data for single actin filaments and two-filament bundles (from Fig. 2 B) are shown for comparison.