Softness, strength and self-repair in intermediate filament networks.

One cellular function of intermediate filaments is to provide cells with compliance to small deformations while strengthening them when large stresses are applied. How IFs accomplish this mechanical role is revealed by recent studies of the elastic properties of single IF protein polymers and by viscoelastic characterization of the networks they form. IFs are unique among cytoskeletal filaments in withstanding large deformations. Single filaments can stretch to more than 3 times their initial length before breaking, and gels of IF withstand strains greater than 100% without damage. Even after mechanical disruption of gels formed by crossbridged neurofilaments, the elastic modulus of these gels rapidly recovers under conditions where gels formed by actin filaments are irreversibly ruptured. The polyelectrolyte properties of IFs may enable crossbridging by multivalent counterions, but identifying the mechanisms by which IFs link into bundles and networks in vivo remains a challenge.

[1]  P. Janmey,et al.  The interaction of neurofilaments with the microtubule motor cytoplasmic dynein. , 2004, Molecular biology of the cell.

[2]  M. Omary,et al.  Cellular integrity plus: organelle-related and protein-targeting functions of intermediate filaments. , 2005, Trends in cell biology.

[3]  H. Isambert,et al.  Flexibility of actin filaments derived from thermal fluctuations. Effect of bound nucleotide, phalloidin, and muscle regulatory proteins , 1995, The Journal of Biological Chemistry.

[4]  G. Bloom,et al.  Cross‐Linking of Intermediate Filaments to Microtubules by Microtubule‐Associated Protein 2 , 1985, Annals of the New York Academy of Sciences.

[5]  J Langowski,et al.  Assessing the flexibility of intermediate filaments by atomic force microscopy. , 2004, Journal of molecular biology.

[6]  P. Janmey,et al.  Viscoelastic properties of vimentin compared with other filamentous biopolymer networks , 1991, The Journal of cell biology.

[7]  Ning Wang,et al.  Mechanics of vimentin intermediate filaments , 2004, Journal of Muscle Research & Cell Motility.

[8]  Sebastian Rammensee,et al.  Negative normal stress in semiflexible biopolymer gels. , 2007, Nature materials.

[9]  J. Julien,et al.  Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density , 2002, The Journal of cell biology.

[10]  U. Aebi,et al.  Exploring the mechanical properties of single vimentin intermediate filaments by atomic force microscopy. , 2006, Journal of molecular biology.

[11]  L. Kreplak,et al.  Investigation of the morphology of intermediate filaments adsorbed to different solid supports. , 2005, Journal of structural biology.

[12]  J. Eyer,et al.  Properties of highly viscous gels formed by neurofilaments in vitro. A possible consequence of a specific inter-filament cross-bridging. , 1987, The Biochemical journal.

[13]  Yiider Tseng,et al.  A Direct Interaction between Actin and Vimentin Filaments Mediated by the Tail Domain of Vimentin* , 2006, Journal of Biological Chemistry.

[14]  P. Janmey,et al.  Mechanical Effects of Neurofilament Cross-bridges , 1996, The Journal of Biological Chemistry.

[15]  Rajendrani Mukhopadhyay,et al.  Molecular mechanisms for organizing the neuronal cytoskeleton. , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[16]  Jay X. Tang,et al.  Counterion induced bundle formation of rodlike polyelectrolytes , 1996 .

[17]  M. Kellermayer,et al.  Nanomechanical properties of desmin intermediate filaments. , 2006, Journal of structural biology.

[18]  Masaaki Ito,et al.  Human hair keratin-associated proteins. , 2005, The journal of investigative dermatology. Symposium proceedings.

[19]  M. Pekny,et al.  Astrocyte intermediate filaments in CNS pathologies and regeneration , 2004, The Journal of pathology.

[20]  G. Wiche,et al.  Plectin: A Cytolinker by Design , 1999, Biological chemistry.

[21]  D. Wirtz,et al.  The mechanical properties of simple epithelial keratins 8 and 18: discriminating between interfacial and bulk elasticities. , 2003, Journal of structural biology.

[22]  P. Janmey,et al.  Viscoelasticity of intermediate filament networks. , 1998, Sub-cellular biochemistry.

[23]  Jochen Guck,et al.  Viscoelastic properties of individual glial cells and neurons in the CNS , 2006, Proceedings of the National Academy of Sciences.

[24]  P. Janmey,et al.  Flexibility transitions and looped adsorption of wormlike chains , 2005 .

[25]  Yiider Tseng,et al.  Local dynamics and viscoelastic properties of cell biological systems , 2002 .

[26]  R. Merkel,et al.  Desmin filaments studied by quasi-elastic light scattering. , 1999, Biophysical journal.

[27]  J. Ferry,et al.  Flexibility of myosin rod determined from dilute solution viscoelastic measurements. , 1982, Biochemistry.

[28]  P. Janmey,et al.  Bidirectional translocation of neurofilaments along microtubules mediated in part by dynein/dynactin. , 2000, Molecular biology of the cell.

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

[30]  T. Shea,et al.  Neurofilaments can undergo axonal transport and cytoskeletal incorporation in a discontinuous manner. , 2005, Cell motility and the cytoskeleton.

[31]  E. Fuchs,et al.  The cytoskeleton and disease: genetic disorders of intermediate filaments. , 1996, Annual review of genetics.

[32]  D. Wirtz,et al.  Keratin Filament Suspensions Show Unique Micromechanical Properties* , 1999, The Journal of Biological Chemistry.

[33]  N. Hirokawa,et al.  Structure of the peripheral domains of neurofilaments revealed by low angle rotary shadowing. , 1988, Journal of molecular biology.

[34]  J. Howard,et al.  Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape , 1993, The Journal of cell biology.

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

[36]  J. Eyer,et al.  Influence of the phosphorylation state of neurofilament proteins on the interactions between purified filaments in vitro. , 1988, The Biochemical journal.

[37]  Ueli Aebi,et al.  Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular Scaffolds. , 2003, Annual review of biochemistry.

[38]  D H Wachsstock,et al.  Cross-linker dynamics determine the mechanical properties of actin gels. , 1994, Biophysical journal.

[39]  T. Shea,et al.  Neurofilaments Consist of Distinct Populations That Can Be Distinguished by C-Terminal Phosphorylation, Bundling, and Axonal Transport Rate in Growing Axonal Neurites , 2001, The Journal of Neuroscience.

[40]  G. Gundersen,et al.  Kinesin Is a Candidate for Cross-bridging Microtubules and Intermediate Filaments , 1998, The Journal of Biological Chemistry.

[41]  P. Janmey,et al.  Domain unfolding in neurofilament sidearms: effects of phosphorylation and ATP , 2002, FEBS letters.

[42]  N. Hirokawa,et al.  Cross-linker system between neurofilaments, microtubules and membranous organelles in frog axons revealed by the quick-freeze, deep-etching method , 1982, The Journal of cell biology.

[43]  Sanjay Kumar,et al.  Role of long‐range repulsive forces in organizing axonal neurofilament distributions: Evidence from mice deficient in myelin‐associated glycoprotein , 2002, Journal of neuroscience research.

[44]  P. Janmey,et al.  Viscoelasticity of F-actin and F-actin/gelsolin complexes. , 1988, Biochemistry.

[45]  M. Omary,et al.  Intermediate filament proteins and their associated diseases. , 2004, The New England journal of medicine.

[46]  Christian Riekel,et al.  The mechanical properties of hydrated intermediate filaments: insights from hagfish slime threads. , 2003, Biophysical journal.

[47]  D Lerche,et al.  The mechanical properties of actin gels. Elastic modulus and filament motions. , 1994, The Journal of biological chemistry.

[48]  D. Parry,et al.  Fibrous proteins: new structural and functional aspects revealed. , 2005, Advances in protein chemistry.

[49]  M. Magnasco,et al.  Measurement of the persistence length of polymerized actin using fluorescence microscopy. , 1993, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[50]  N. Stellwagen,et al.  Flexibility of smooth and skletal tropomyosins , 1989, Biopolymers.

[51]  P. Janmey.  A torsion pendulum for measurement of the viscoelasticity of biopolymers and its application to actin networks. , 1991, Journal of biochemical and biophysical methods.

[52]  Robert D. Goldman,et al.  Rapid Movements of Vimentin on Microtubule Tracks: Kinesin-dependent Assembly of Intermediate Filament Networks , 1998, The Journal of cell biology.

[53]  Sanjay Kumar,et al.  Relating interactions between neurofilaments to the structure of axonal neurofilament distributions through polymer brush models. , 2002, Biophysical journal.

[54]  J. Goldman,et al.  Plectin regulates the organization of glial fibrillary acidic protein in Alexander disease. , 2006, The American journal of pathology.

[55]  R. Pithawalla,et al.  Keratin-like components of gland thread cells modulate the properties of mucus from hagfish (Eptatretus stouti) , 1991, Cell and Tissue Research.

[56]  P. Janmey,et al.  Elongation and fluctuations of semiflexible polymers in a nematic solvent. , 2004, Physical review letters.

[57]  P. Janmey,et al.  Nonlinear elasticity in biological gels , 2004, Nature.

[58]  P. Janmey,et al.  Regulation of neurofilament interactionsin vitro by natural and synthetic polypeptides sharing Lys-Ser-Pro sequences with the heavy neurofilament subunit NF-H: Neurofilament crossbridging by antiparallel sidearm overlapping , 1998, Medical and Biological Engineering and Computing.

[59]  Brian T Helfand,et al.  Intermediate filaments are dynamic and motile elements of cellular architecture , 2004, Journal of Cell Science.

[60]  U Aebi,et al.  Exploring the mechanical behavior of single intermediate filaments. , 2005, Journal of molecular biology.