Stochastic severing of actin filaments by ADF/cofilin controls the emergence of a steady dynamical regime

Actin dynamics (ie: polymerization/depolymerization) powers a large number of cellular processes. However, a great deal remains to be learned in order to explain the rapid actin filament turnover observed in vivo. Here, we developed a minimal kinetic model that describes key details of actin filament dynamics in the presence of ADF/cofilin. We limited the molecular mechanism to (1) the spontaneous growth of filaments by polymerization of actin monomers, (2) the ageing of actin subunits in filaments, (3) the cooperative binding of ADF/cofilin to actin filament subunits, and (4) filament severing by ADF/cofilin. First, from numerical simulations and mathematical analysis, we find that the average filament length, < L >, is controlled by the concentration of actin monomers (power law: 5/6) and ADF/cofilin (power law: -2/3). We also showed that the average subunit residence time inside the filament, < T >, depends on the actin monomer (power law: -1/6) and ADF/cofilin (power law: -2/3) concentrations. In addition, filament length fluctuations are ~ 20% of the average filament length. Moreover, ADF/cofilin fragmentation while modulating filament length keeps filaments in a high molar ratio of ATP- or ADP-Pi- versus ADP-bound subunits. This latter property has a protecting effect against a too high severing activity of ADF/cofilin. We propose that the activity of ADF/cofilin in vivo is under the control of an affinity gradient that builds up dynamically along growing actin filaments. Our analysis shows that ADF/cofilin regulation maintains actin filaments in a highly dynamical state compatible with the cytoskeleton dynamics observed in vivo.