Engineering amyloid fibrils from β-solenoid proteins for biomaterials applications.

Nature provides numerous examples of self-assembly that can potentially be implemented for materials applications. Considerable attention has been given to one-dimensional cross-β or amyloid structures that can serve as templates for wire growth or strengthen materials such as glue or cement. Here, we demonstrate controlled amyloid self-assembly based on modifications of β-solenoid proteins. They occur naturally in several contexts (e.g., antifreeze proteins, drug resistance proteins) but do not aggregate in vivo due to capping structures or distortions at their ends. Removal of these capping structures and regularization of the ends of the spruce budworm and rye grass antifreeze proteins yield micron length amyloid fibrils with predictable heights, which can be a platform for biomaterial-based self-assembly. The design process, including all-atom molecular dynamics simulations, purification, and self-assembly procedures are described. Fibril formation with the predicted characteristics is supported by evidence from thioflavin-T fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy. Additionally, we find evidence for lateral assembly of the modified spruce budworm antifreeze fibrils with sufficient incubation time. The kinetics of polymerization are consistent with those for other amyloid formation reactions and are relatively fast due to the preformed nature of the polymerization nucleus.

[1]  Anthony A Kossiakoff,et al.  X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers. , 2008, Journal of the American Chemical Society.

[2]  Michael A Kennedy,et al.  The 2A resolution crystal structure of HetL, a pentapeptide repeat protein involved in regulation of heterocyst differentiation in the cyanobacterium Nostoc sp. strain PCC 7120. , 2009, Journal of structural biology.

[3]  Michael J. Kuiper,et al.  β-Helix structure and ice-binding properties of a hyperactive antifreeze protein from an insect , 2000, Nature.

[4]  H. Erickson,et al.  Kinetics of protein-protein association explained by Brownian dynamics computer simulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  U. Baxa,et al.  The N-terminal prion domain of Ure2p converts from an unfolded to a thermally resistant conformation upon filament formation. , 2004, Journal of molecular biology.

[6]  J T Finch,et al.  Amyloid fibers are water-filled nanotubes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  George B. Benedek,et al.  Temperature dependence of amyloid β-protein fibrillization , 1998 .

[8]  Eric R. Kandel,et al.  Aplysia CPEB Can Form Prion-like Multimers in Sensory Neurons that Contribute to Long-Term Facilitation , 2010, Cell.

[9]  David W. Colby,et al.  Natural and synthetic prion structure from X-ray fiber diffraction , 2009, Proceedings of the National Academy of Sciences.

[10]  Chan Beum Park,et al.  Insulin amyloid fibrillation at above 100 degrees C: new insights into protein folding under extreme temperatures. , 2004, Protein science : a publication of the Protein Society.

[11]  Matthew R Chapman,et al.  Curli biogenesis and function. , 2006, Annual review of microbiology.

[12]  Fred E. Cohen,et al.  Evidence for assembly of prions with left-handed β-helices into trimers , 2004 .

[13]  Tuomas P. J. Knowles,et al.  An Analytical Solution to the Kinetics of Breakable Filament Assembly , 2009, Science.

[14]  Kersten S. Rabe,et al.  Orthogonal protein decoration of DNA origami. , 2010, Angewandte Chemie.

[15]  K. Myambo,et al.  Processing of the initiation methionine from proteins: properties of the Escherichia coli methionine aminopeptidase and its gene structure , 1987, Journal of bacteriology.

[16]  D. Cox,et al.  Left handed beta helix models for mammalian prion fibrils. , 2008, Prion.

[17]  Chan Beum Park,et al.  High stability of self‐assembled peptide nanowires against thermal, chemical, and proteolytic attacks , 2010, Biotechnology and bioengineering.

[18]  Sichun Yang,et al.  Prion disease: exponential growth requires membrane binding. , 2006, Biophysical journal.

[19]  B. Sykes,et al.  Disulfide bond mapping and structural characterization of spruce budworm antifreeze protein. , 1998, European journal of biochemistry.

[20]  C. Ionescu-Zanetti,et al.  Mechanism of thioflavin T binding to amyloid fibrils. , 2005, Journal of structural biology.

[21]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[22]  B. Wallace,et al.  Protein secondary structure analyses from circular dichroism spectroscopy: methods and reference databases. , 2008, Biopolymers.

[23]  Alan Brown,et al.  Expression and characterization of an antifreeze protein from the perennial rye grass, Lolium perenne. , 2011, Cryobiology.

[24]  Christopher M Dobson,et al.  Spatial persistence of angular correlations in amyloid fibrils. , 2006, Physical review letters.

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

[26]  C. Ionescu-Zanetti,et al.  Monitoring the assembly of Ig light-chain amyloid fibrils by atomic force microscopy. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P. Vassar,et al.  Fluorescent stains, with special reference to amyloid and connective tissues. , 1959, Archives of pathology.

[28]  B. Berne.  Interpretation of the light scattering from long rods. , 1974, Journal of molecular biology.

[29]  Meital Reches,et al.  Casting Metal Nanowires Within Discrete Self-Assembled Peptide Nanotubes , 2003, Science.

[30]  R. M. A. Sullan,et al.  Nanoscale structures and mechanics of barnacle cement , 2009, Biofouling.

[31]  Olesia V. Moroz,et al.  Short peptides self-assemble to produce catalytic amyloids , 2014, Nature chemistry.

[32]  Chan Beum Park,et al.  Insulin amyloid fibrillation at above 100°C: New insights into protein folding under extreme temperatures , 2004 .

[33]  M. Chapman,et al.  Amyloids: friend or foe? , 2008, Journal of Alzheimer's disease : JAD.

[34]  J. Kovács,et al.  Reversible heat-induced dissociation of β2-microglobulin amyloid fibrils. , 2011, Biochemistry.

[35]  H. Levine,et al.  Thioflavine T interaction with synthetic Alzheimer's disease β‐amyloid peptides: Detection of amyloid aggregation in solution , 1993, Protein science : a publication of the Protein Society.

[36]  Z. Jia,et al.  A beta-helical antifreeze protein isoform with increased activity. Structural and functional insights. , 2002, The Journal of biological chemistry.

[37]  D. Teplow,et al.  Temperature dependence of amyloid beta-protein fibrillization. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Christopher B. Marshall,et al.  Antifreeze protein from freeze-tolerant grass has a beta-roll fold with an irregularly structured ice-binding site. , 2012, Journal of molecular biology.

[39]  F. Ferrone,et al.  Analysis of protein aggregation kinetics. , 1999, Methods in enzymology.

[40]  Alexander K. Buell,et al.  Population of nonnative states of lysozyme variants drives amyloid fibril formation. , 2011, Journal of the American Chemical Society.

[41]  N. Greenfield.  Using circular dichroism spectra to estimate protein secondary structure , 2007, Nature Protocols.

[42]  L. Lanier,et al.  Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family , 2001, Immunogenetics.

[43]  Adrien Treuille,et al.  Predicting protein structures with a multiplayer online game , 2010, Nature.

[44]  U. Sleytr,et al.  Crystalline bacterial cell surface layers (S-layers): from cell structure to biomimetics. , 1996, Progress in biophysics and molecular biology.

[45]  A. Belcher,et al.  Nanostructure design of amorphous FePO4 facilitated by a virus for 3 V lithium ion battery cathodes , 2011 .

[46]  N. Sreerama,et al.  Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set. , 2000, Analytical biochemistry.

[47]  George Georgiou,et al.  Virus-Based Toolkit for the Directed Synthesis of Magnetic and Semiconducting Nanowires , 2004, Science.

[48]  Yogendra Pratap Singh,et al.  Amyloid peptides and proteins in review. , 2007, Reviews of physiology, biochemistry and pharmacology.

[49]  L. Serpell,et al.  Spider silk and amyloid fibrils: a structural comparison. , 2007, Macromolecular bioscience.

[50]  V. Uversky,et al.  Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism. , 2001, Biochemistry.

[51]  N. Seeman,et al.  DNA-Templated Self-Assembly of Metallic Nanocomponent Arrays on a Surface , 2004 .

[52]  S. Provencher,et al.  Estimation of globular protein secondary structure from circular dichroism. , 1981, Biochemistry.

[53]  F. Cohen,et al.  Evidence for assembly of prions with left-handed beta-helices into trimers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[54]  A. Woolley,et al.  Fabrication of DNA-templated Te and Bi2Te3 nanowires by galvanic displacement. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[55]  N. Seeman.  Nanomaterials based on DNA. , 2010, Annual review of biochemistry.

[56]  T. Scheibel,et al.  Influence of repeat numbers on self-assembly rates of repetitive recombinant spider silk proteins. , 2014, Journal of structural biology.

[57]  Robert W. Janes,et al.  Modern techniques for circular dichroism and synchrotron radiation circular dichroism spectroscopy: 1 , 2009 .

[58]  Alexander K. Buell,et al.  Nanostructured films from hierarchical self-assembly of amyloidogenic proteins. , 2010, Nature nanotechnology.

[59]  C. Blake,et al.  The structure of amyloid fibrils by electron microscopy and X-ray diffraction. , 1997, Advances in protein chemistry.

[60]  Ronald Wetzel,et al.  Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[61]  M. Biancalana,et al.  Molecular mechanism of Thioflavin-T binding to amyloid fibrils. , 2010, Biochimica et biophysica acta.

[62]  H. Jaeger,et al.  Conducting nanowires built by controlled self-assembly of amyloid fibers and selective metal deposition , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[63]  David Eisenberg,et al.  In Brief , 2009, Nature Reviews Neuroscience.

[64]  H. Levine.  Quantification of beta-sheet amyloid fibril structures with thioflavin T. , 1999, Methods in enzymology.

[65]  Shuguang Zhang.  Fabrication of novel biomaterials through molecular self-assembly , 2003, Nature Biotechnology.

[66]  K. Sakaguchi,et al.  Formation of Functionalized Nanowires by Control of Self‐Assembly Using Multiple Modified Amyloid Peptides , 2013 .

[67]  Markus J Buehler,et al.  Nanomechanics of functional and pathological amyloid materials. , 2011, Nature nanotechnology.

[68]  Mark Bathe,et al.  A primer to scaffolded DNA origami , 2011, Nature Methods.

[69]  D. Cox,et al.  Left handed β helix models for mammalian prion fibrils , 2008 .

[70]  Paul Tavan,et al.  Molecular dynamics simulations indicate a possible role of parallel beta-helices in seeded aggregation of poly-Gln. , 2005, Biophysical journal.

[71]  Beat H. Meier,et al.  Amyloid Fibrils of the HET-s(218–289) Prion Form a β Solenoid with a Triangular Hydrophobic Core , 2008, Science.

[72]  Ronald Wetzel,et al.  Polyglutamine aggregation nucleation: Thermodynamics of a highly unfavorable protein folding reaction , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[73]  N. Ashkenasy,et al.  Introducing charge transfer functionality into prebiotically relevant β-sheet peptide fibrils. , 2014, Chemical communications.

[74]  G. W. Buchko,et al.  Characterization of two potentially universal turn motifs that shape the repeated five‐residues fold—Crystal structure of a lumenal pentapeptide repeat protein from Cyanothece 51142 , 2006, Protein science : a publication of the Protein Society.