ATP hydrolysis stimulates large length fluctuations in single actin filaments

Abstract

Polymerization dynamics of single actin filaments is investigated theoretically using a stochastic model that takes into account the hydrolysis of ATP-actin subunits, the geometry of actin filament tips, and the lateral interactions between the monomers as well as the processes at both ends of the polymer. Exact analytical expressions are obtained for the mean growth velocity, for the dispersion in the length fluctuations, and the nucleotide composition of the actin filaments. It is found that the ATP hydrolysis has a strong effect on dynamic properties of single actin filaments. At high concentrations of free actin monomers, the mean size of the unhydrolyzed ATP-cap is very large, and the dynamics is governed by association/dissociation of ATP-actin subunits. However, at low concentrations the size of the cap becomes finite, and the dissociation of ADP-actin subunits makes a significant contribution to overall dynamics. Actin filament length fluctuations reach a sharp maximum at the boundary between two dynamic regimes, and this boundary is always larger than the critical concentration for the actin filament's growth at the barbed end, assuming the sequential release of phosphate. Random and sequential mechanisms of hydrolysis are compared, and it is found that they predict qualitatively similar dynamic properties at low and high concentrations of free actin monomers with some deviations near the critical concentration. The possibility of attachment and detachment of oligomers in actin filament's growth is also discussed. Our theoretical approach is successfully applied to analyze the latest experiments on the growth and length fluctuations of individual actin filaments. © 2006 by the Biophysical Society.