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Biophys. J. BioFAST: First Published December 7, 2007. doi:10.1529/biophysj.107.121988
© 2007 by the Biophysical Society.

A more recent version of this article appeared on March 15, 2008.
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BIOPHYSICAL THEORY AND MODELING

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

Jeremy Roland 1, Julien Berro 1, Alphee Michelot 1, Laurent Blanchoin 1 and Jean-Louis Martiel 1*

1 Université Joseph Fourier, France

* To whom correspondence should be addressed. E-mail: jean-louis.martiel{at}imag.fr.

Submitted on September 13, 2007
Revised on October 5, 2007
Accepted on 19 November 2007


  Abstract
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.

Key Words: ADF/cofilin, Monte Carlo simulations, actin, cytoskeleton dynamics., filament fluctuations






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Copyright © 2007 by the Biophysical Society.