Quantitative Analysis of the Self-Assembly Strategies of Intermediate Filaments from Tetrameric Vimentin
Issue No. 03 - May-June (2012 vol. 9)
DOI Bookmark: http://doi.ieeecomputersociety.org/10.1109/TCBB.2011.154
E. Czeizler , Comput. Syst. Biol. Lab., Univ. of Helsinki, Helsinki, Finland
A. Mizera , Inst. of Fundamental Technol. Res., Warsaw, Poland
E. Czeizler , Sch. of Sci., Dept. of Inf. & Comput. Sci., Aalto Univ., Aalto, Finland
R-J Back , Dept. of Inf. Technol., Abo Akademi Univ., Turku, Finland
J. E. Eriksson , Turku Centre for Biotechnol., Abo Akademi Univ., Turku, Finland
I. Petre , Dept. of Inf. Technol., Abo Akademi Univ., Turku, Finland
In vitro assembly of intermediate filaments from tetrameric vimentin consists of a very rapid phase of tetramers laterally associating into unit-length filaments and a slow phase of filament elongation. We focus in this paper on a systematic quantitative investigation of two molecular models for filament assembly, recently proposed in (Kirmse et al. J. Biol. Chem. 282, 52 (2007), 18563-18572), through mathematical modeling, model fitting, and model validation. We analyze the quantitative contribution of each filament elongation strategy: with tetramers, with unit-length filaments, with longer filaments, or combinations thereof. In each case, we discuss the numerical fitting of the model with respect to one set of data, and its separate validation with respect to a second, different set of data. We introduce a high-resolution model for vimentin filament self-assembly, able to capture the detailed dynamics of filaments of arbitrary length. This provides much more predictive power for the model, in comparison to previous models where only the mean length of all filaments in the solution could be analyzed. We show how kinetic observations on low-resolution models can be extrapolated to the high-resolution model and used for lowering its complexity.
self-assembly, molecular biophysics, physiological models, proteins, extrapolation, quantitative analysis, self-assembly strategy, intermediate filaments, molecular models, in-vitro assembly, filament assembly, mathematical modeling, filament elongation strategy, unit-length filaments, numerical model fitting, high-resolution model, vimentin filament self-assembly, low-resolution model, Assembly, Numerical models, Mathematical model, Computational modeling, Data models, Proteins, Biological system modeling, filament length distribution., Mathematical modeling, protein self-assembly, quantitative self-assembly strategies, model resolution, sensitivity analysis
E. Czeizler, A. Mizera, E. Czeizler, R. Back, J. E. Eriksson and I. Petre, "Quantitative Analysis of the Self-Assembly Strategies of Intermediate Filaments from Tetrameric Vimentin," in IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 9, no. , pp. 885-898, 2012.