Simulations of RFP-cNLS diffusion and import recapitulate aspects of the in vitro data. (A) A mathematical model of RFP-cNLS transport was constructed that included cytoplasmic diffusion, facilitated nuclear import, diffusion across the NPC, and the ability to vary myotube width. The cytoplasmic production of RFP-cNLS decreased linearly from one boundary of the simulation (modeling a transfected nucleus at the center of the myotube), and a reflecting boundary was imposed at the terminus of the myotube. (B) The relative quantities of RFP-cNLS proteins within the simulated myonuclei were determined at different simulation times using a baseline parameter set (see also SI Appendix, Table S1). (C–G) The effects of varying different model parameters on RFP-cNLS propagation were determined for the cytoplasmic diffusion coefficient, D (C); the coefficient governing diffusion across the NPC, DN (D); the nuclear import coefficient, I (E); the myotube width, W (F); and the nuclear import coefficient with nonzero diffusion across the NPC (G).