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ActinSim
Project on Simulation of Actin Polymerization
April 2006 - April 2007


IMPORTANT: This page is obsolete and left only for the reliability!
The new and updated version is avalable at actinsim.uni.lu


 


  About the project

      Motivation. The high supra-molecular and organisational complexity of the cell cytoskeleton renders it difficult to study actin-based movement in a cellular environment. It is extremely important to understand how actin polymerisation generates forces and movements. Several biophysical models were proposed for the mechanisms by which actin filament assembly generates force that is translated into the movement (Mogilner and Rubinstein, 2005; Paluch et al., 2005; Alberts 2004). Among them the approach of stochastic simulations seems to have considerable potential since it provides an intuitively clear wpicture of the dynamic processes in the cell regulatory system. Moreover, its results are often in closer approximations to the molecular reality than the results of classical analytical models based on a set of continuous deterministic differential equations. However, so fare, no comprehensive and systematic comparative study or evaluation of modelling approaches used in cytoskeleton research is available.
    Goal. The goal of our work is to develop an advanced computer-simulation approach, based on stochastic and analytical modelling algorithms, for the simulation and analysis of the actin filament formation and its effect on small-bodies (beads, bacteria) motility in terms of forces and velocities.
    Methods. Our approach combines stochastic simulations of the biochemical reactions, mechanical filament-filament interactions and force-filed constrains. The biochemical reactions are simulated using the modified Gillespie's method with the discrete time introduced. The mechanical model, including filament-filament and filament-bead (or bacteria) interactions, viscous friction and Brownian effects is realized to simulate the forces in the considered system. The simulation models and computation algorithms are developed as the C++ classes and integrated in the stand-alone executable software package. The mathematical package Mathematica 6 is used to validate the simulation models by comparison of simulation results with the numerical solution of the ODE models.
    Results. A simulation model of a simplified biochemical network that reproduces an actin-polymerization process in a limited volume of a cell has been developed. The model generates 8 first-order chemical reactions which are linked with 3D spatial model of the system, which includes filaments and other solid bodies (beads or bacteria). The homogeneity of the concentrations in the volume is validated via Monte Carlo simulation of diffusion. The preliminary results of our simulations, in particular some selected biochemical parameters, like the rate of polymerization and the monomer diffusion constant, are in good agreement with those published elsewhere and with the results of FRAP experiments carried out in our lab on some selected actin-polymerization systems.

      This work was financed by Fond National de la Recherche (FNR), Luxembourg

 


  Download the ActinSimChem sofware and classes

 


  Download other sofware

 


  Reports and other actin-related information

      Final report on FNR-project
      Manual on ActinSimChem
      Report and short manual on ActinPyreneFit
      Abstract:
      Nazarov P.V., Yatskou M.M., Barsukov E.A., Ivashkevich E.V., Golovaty A.A., Apanasovich V.V., Friederich E. Developing mathematical models, algorithms and programming tools for analysis of actin-based motility. 3rd Wolfgang Pauli International Workshop on Mathematical Modelling of Actin-Based Motility, Vienna, Austria, November 6-8, 2006, p. 13.
      Article:
      Halavatyi A.A., Nazarov P.V., Yatskou M.M., Apanasovich V.V., Friederich E Simulation and analytical models for the analysis of in vitro actin polymerization. Proceedings of the Eighth International Conference "Computer Data Analysis and Modeling: Complex Stochastic Data and Systems", Vol. 2, Publishing center BSU, 2007, Minsk, p. 184-187.

      Article: (see actinsim.uni.lu for the updated software)
      Halavatyi A., Nazarov P., Medves S., van Troys M., Ampe C., Yatskou M., E. Friederich. An Integrative Simulation Model Linking Major Biochemical reactions of actin-polymerization to structural properties of actin filaments. Biophys. Chem., 2009, v. 140, p. 24-34.

 


  Authors

      Supervisors:
      Prof. Evelyne Friederich (University of Luxembourg)   evelyne.friederichuni.lu
      Dr. Mikalai Yatskou (University of Luxembourg)   mikalai.yatskouuni.lu
      Researchers:
      Dr. Petr Nazarov (CRP-Sante, Luxembourg, and Belarusian State University)  petr.nazarovcrp-sante.lu
      Aliaksandr Halavatyi (Belarusian State University)  alexander.golovatyrambler.ru
      Engineers:
      Eugene Barsukov (Belarusian State University)
      Eugene Ivashkevich (Belarusian State University)

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