Quantitative analysis of the self-assembly strategies of intermediate filaments from tetrameric vimentin

Eugen Czeizler, A Mizera, E Czeizler, Ralph-Johan Back, John Eriksson, Ion Petre

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    Abstract

    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.
    Original languageUndefined/Unknown
    Pages (from-to)885–898
    JournalIEEE/ACM Transactions on Computational Biology and Bioinformatics
    Volume9
    Issue number3
    DOIs
    Publication statusPublished - 2000
    MoE publication typeA1 Journal article-refereed

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