The contribution of the N- and C- terminal domains to the stretching properties of intermediate filaments
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The contribution of the N- and C- terminal domains to the stretching properties of intermediate filaments Laurent Kreplak Department of Physics and Atmospheric Science, Dalhousie University, Halifax, NS B3H 3J5, Canada ABSTRACT The animal cell cytoskeleton consists of three interconnected filament systems: actin containing microfilaments (MFs), microtubules (MTs), and intermediate filaments (IFs). Among these three filaments systems, IFs are the only one that show high extensibility at both the single filament and network levels. In this work, I am presenting a simple model of IFs extensibility based on the current structural knowledge of the filaments. The only extra information added to this model compared to previous ones is the fact that the unfolded N- and C-termini of IF proteins are sandwiched between adjacent coiled-coil rod domains within the filaments. Since we know the contour length and typical persistence length of these unfolded termini, it is possible to predict the persistence length of a single filament, its maximal extensibility and the onset of coiled-coil unfolding. The predictions of the model are in good agreement with experiments on single desmin IFs stretched on a surface by AFM and on vimentin and desmin networks probed by rheology. INTRODUCTION Over the last twenty years the intermediate filaments (IFs) cytoskeleton has emerged as a key player in imparting mechanical stability to cells and tissues. The key feature of IF networks compared to actin and microtubule ones are their extensibility and ability to strain-harden [1]. However the molecular origin of these unique mechanical properties remains unclear [2]. One issue has been the lack of structural data on IF proteins and on the way they assemble into filaments. Most of the available structural information is confined to the well conserved central alpha-helical coiled-coil rod domain of IF proteins. The rod domain is also flanked by N- and Cterminal domains that should behave as unfolded polypeptide based on sequence analysis. These domains are highly variable among IFs but their presence is critical for proper filament assembly [3]. Using electron paramagnetic resonance spectroscopy, Aziz et al. demonstrated that the Nterminal domain of vimentin binds to its rod domain in a phosphorylation dependent manner [1]. Based on this new finding, I develop a structural model of IF mechanics that treats the N- and Ctermini as entropic spring following the idea of Buehler and Ackbarow [4] . So far there are two main models of IF mechanics based on hard alpha-keratin fibers data [5] and on hagfish slime threads data [6]. The first one only takes into account the mechanical response of the rod domains, whereas the second one treats the terminal domains as entropic springs in series with the rod domains. The model presented here builds on the idea of Fudge et al. [6] taking into account the most recent structural data [1]. THEORY
The model is built for a murine desmin IF containing n = 46 chains per cross-section with a radius R of 6.
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