The coordination of actin-binding proteins (ABPs) is essential for forming a wide range of actin structures that drive vital cellular processes. The severing proteins, cofilins, bind actin cooperatively with affinity dependent on the subunit’s nucleotide state, and sever less at both low and high cofilin concentrations. How this nucleotide-state-dependent severing shapes filament-length distributions is unclear. Our stochastic model combining polymerization, phosphate release, hydrolysis-dependent cofilin binding, and severing, captures key observations: non-monotonic change in average filament length and variation in cap size with increasing cofilin and actin concentration. These trends emerge from tunable heterogeneity in the cofilin-decorated and undecorated subunits along with a long-tailed distribution of cofilin-decorated clusters within a filament. The model also predicts a crossover of filament-length distributions from symmetric to long-tailed with varying cofilin concentration. We identify regimes where our model simplifies to a coarse-grained model, mathematically predicting that the distribution of undecorated subunits is exponential, whose decay constant depends on actin and cofilin concentrations. Thus, structural heterogeneity in subunit arrangements can modulate actin-length variability.
Ray et al. (Sun,) studied this question.