Assembly kinetics determine the structure of keratin networks

Living cells exhibit an enormous bandwidth of mechanical and morphological properties that are mainly determined by the cytoskeleton. In metazoan cells this composite network is constituted of three different types of filamentous systems: actin filaments, microtubules and intermediate filaments. Keratin-type intermediate filaments are an essential component of epithelial tissues, where they comprise networks of filaments and filament bundles. However, the underlying mechanisms leading to this inherently polymorphic structure remain elusive. Here, we show that keratin filaments form kinetically trapped networks of bundles under near-physiological conditions in vitro. The network structure is determined by the intricate interplay between filament elongation and their lateral association to bundles and clusters.

[1]  Margaret L. Gardel,et al.  Assembly Kinetics Determine the Architecture of α-actinin Crosslinked F-actin Networks , 2012, Nature Communications.

[2]  L Cipelletti,et al.  Slow dynamics and internal stress relaxation in bundled cytoskeletal networks. , 2011, Nature materials.

[3]  J. Urbach,et al.  Size-dependent rheology of type-I collagen networks. , 2010, Biophysical journal.

[4]  T. Aach,et al.  The keratin-filament cycle of assembly and disassembly , 2010, Journal of Cell Science.

[5]  C. Broedersz,et al.  Origins of elasticity in intermediate filament networks. , 2010, Physical review letters.

[6]  R. Windoffer,et al.  Actin-dependent dynamics of keratin filament precursors. , 2009, Cell motility and the cytoskeleton.

[7]  P. Coulombe,et al.  Self-organization of keratin intermediate filaments into cross-linked networks , 2009, The Journal of cell biology.

[8]  A. Bausch,et al.  Structural and viscoelastic properties of actin/filamin networks: cross-linked versus bundled networks. , 2009, Biophysical journal.

[9]  U. Aebi,et al.  Intermediate filaments: primary determinants of cell architecture and plasticity. , 2009, The Journal of clinical investigation.

[10]  W. Wall,et al.  Structural polymorphism in heterogeneous cytoskeletal networks , 2009 .

[11]  W. Arendt,et al.  Simulating the formation of keratin filament networks by a piecewise-deterministic Markov process. , 2009, Journal of theoretical biology.

[12]  A. Bausch,et al.  Internal stress in kinetically trapped actin bundle networks , 2008 .

[13]  S. Hell,et al.  STED microscopy with a supercontinuum laser source. , 2008, Optics express.

[14]  E. Lane,et al.  The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases , 2008, Human mutation.

[15]  R. Windoffer,et al.  p38 MAPK-dependent shaping of the keratin cytoskeleton in cultured cells , 2007, The Journal of cell biology.

[16]  David A Weitz,et al.  The cell as a material. , 2007, Current opinion in cell biology.

[17]  C. Dobson,et al.  Protein misfolding, functional amyloid, and human disease. , 2006, Annual review of biochemistry.

[18]  D A Weitz,et al.  Glioma expansion in collagen I matrices: analyzing collagen concentration-dependent growth and motility patterns. , 2005, Biophysical journal.

[19]  P. Coulombe,et al.  Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds , 2004, Nature Cell Biology.

[20]  S. Manley,et al.  Universal non-diffusive slow dynamics in aging soft matter. , 2003, Faraday discussions.

[21]  M. Omary,et al.  'Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filaments. , 2002, Current opinion in cell biology.

[22]  F. W. Flitney,et al.  Insights into the Dynamic Properties of Keratin Intermediate Filaments in Living Epithelial Cells , 2001, The Journal of cell biology.

[23]  D. Wirtz,et al.  The 'ins' and 'outs' of intermediate filament organization. , 2000, Trends in cell biology.

[24]  U Aebi,et al.  Characterization of distinct early assembly units of different intermediate filament proteins. , 1999, Journal of molecular biology.

[25]  E. Fuchs,et al.  A structural scaffolding of intermediate filaments in health and disease. , 1998, Science.

[26]  W. Franke,et al.  Heterotypic interactions and filament assembly of type I and type II cytokeratins in vitro: viscometry and determinations of relative affinities. , 1997, European journal of cell biology.

[27]  A. Steven,et al.  The mechanism of interaction of filaggrin with intermediate filaments. The ionic zipper hypothesis. , 1993, Journal of molecular biology.

[28]  U Aebi,et al.  Effect of aluminum and other multivalent cations on neurofilaments in vitro: an electron microscopic study. , 1990, Journal of structural biology.

[29]  Monika Mauermann,et al.  Complex formation and kinetics of filament assembly exhibited by the simple epithelial keratins K8 and K18. , 2012, Journal of structural biology.

[30]  C. Safinya,et al.  Gel-expanded to gel-condensed transition in neurofilament networks revealed by direct force measurements. , 2010, Nature materials.

[31]  E. Lane,et al.  Characterization of early assembly intermediates of recombinant human keratins. , 2002, Journal of structural biology.

[32]  Denis Wirtz,et al.  Pairwise assembly determines the intrinsic potential for self-organization and mechanical properties of keratin filaments. , 2002, Molecular Biology of the Cell.

[33]  N. Otsu A threshold selection method from gray level histograms , 1979 .