Structural heterogeneities of self-assembled peptide nanomaterials

We use Fluorescence Lifetime Imaging Microscopy (FLIM) and Second Harmonic Imaging Microscopy (SHIM) to investigate the fundamental molecular mechanisms responsible for nucleation and growth of amyloidogenic-derived nanomaterials. The nanomaterials are assembled from of Amyloid-β(16-22), specifically Ac-KLVFFAE-NH2, the nucleating core of the Alzheimer's Amyloid-β protein. We describe how FLIM and SHIM can be used to follow different nucleation pathways and to quantify structural heterogeneities within these complex nanomaterials. New evidence suggests that different structures emerge from distinct nucleation pathways and these insights inform our understanding of the peptide self-assembly mechanisms. We discuss these insights in the context of a top down understanding of amyloidogenic diseases, the bottom up control of functional nanomaterials and the discovery of realtime structural indicators for nanofabrication strategies.

[1]  V. Conticello,et al.  Exploiting amyloid fibril lamination for nanotube self-assembly. , 2003, Journal of the American Chemical Society.

[2]  J. Snyder,et al.  Facial symmetry in protein self-assembly. , 2008, Journal of the American Chemical Society.

[3]  G. Rosenman,et al.  Bioinspired peptide nanotubes: deposition technology, basic physics and nanotechnology applications , 2011, Journal of peptide science : an official publication of the European Peptide Society.

[4]  P. Baldi,et al.  The Absence of Favorable Aromatic Interactions between β-Sheet Peptides , 2005 .

[5]  J. J. Balbach,et al.  Increasing the amphiphilicity of an amyloidogenic peptide changes the beta-sheet structure in the fibrils from antiparallel to parallel. , 2004, Biophysical journal.

[6]  A. Kelarakis,et al.  Self-assembly and hydrogelation of an amyloid peptide fragment. , 2008, Biochemistry.

[7]  S. Santini,et al.  In Silico Assembly of Alzheimer's Aβ16-22 Peptide into β-Sheets , 2004 .

[8]  J. Hoh,et al.  Amyloid‐β aggregates formed at polar–nonpolar interfaces differ from amyloid‐β protofibrils produced in aqueous buffers , 2005 .

[9]  R. Leapman,et al.  Amyloid Fibril Formation by Aβ16-22, a Seven-Residue Fragment of the Alzheimer's β-Amyloid Peptide, and Structural Characterization by Solid State NMR† , 2000 .

[10]  R. Nussinov,et al.  Beta2-microglobulin amyloid fragment organization and morphology and its comparison to Abeta suggests that amyloid aggregation pathways are sequence specific. , 2008, Biochemistry.

[11]  R. Wetzel,et al.  Polymorphism in the intermediates and products of amyloid assembly. , 2007, Current opinion in structural biology.

[12]  S. Decatur.  Elucidation of Residue-Level Structure and Dynamics of Polypeptides via Isotope-Edited Infrared Spectroscopy , 2006 .

[13]  W Seth Childers,et al.  Peptide membranes in chemical evolution. , 2009, Current opinion in chemical biology.

[14]  David Barlam,et al.  Self-assembled peptide nanotubes are uniquely rigid bioinspired supramolecular structures. , 2005, Nano letters.

[15]  A. Mehta,et al.  Templating molecular arrays in amyloid's cross-beta grooves. , 2009, Journal of the American Chemical Society.

[16]  S. Decatur,et al.  Experimental evidence for the reorganization of beta-strands within aggregates of the Abeta(16-22) peptide. , 2005, Journal of the American Chemical Society.

[17]  A. Mehta,et al.  Controlling amyloid growth in multiple dimensions , 2006, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[18]  Nitin Chaudhary,et al.  Impact on the replacement of Phe by Trp in a short fragment of Aβ amyloid peptide on the formation of fibrils , 2011, Journal of peptide science : an official publication of the European Peptide Society.

[19]  A. Morinaga,et al.  Critical role of interfaces and agitation on the nucleation of Abeta amyloid fibrils at low concentrations of Abeta monomers. , 2010, Biochimica et biophysica acta.

[20]  A. Alexandrescu,et al.  Heterogeneous amylin fibril growth mechanisms imaged by total internal reflection fluorescence microscopy. , 2011, Biochemistry.

[21]  Leslie M Loew,et al.  Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms , 2003, Nature Biotechnology.

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

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

[24]  K. Berland,et al.  Light harvesting antenna on an amyloid scaffold. , 2008, Chemical communications.

[25]  D. Gordon,et al.  Design and characterization of a membrane permeable N-methyl amino acid-containing peptide that inhibits Aβ1–40 fibrillogenesis , 2008 .

[26]  D. Holtzman,et al.  In situ atomic force microscopy study of Alzheimer's beta-amyloid peptide on different substrates: new insights into mechanism of beta-sheet formation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Gerald H Pollack,et al.  Surfaces and interfacial water: evidence that hydrophilic surfaces have long-range impact. , 2006, Advances in colloid and interface science.

[28]  Carl W. Cotman,et al.  Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis , 2003, Science.

[29]  J. Snyder,et al.  Cross-strand pairing and amyloid assembly. , 2008, Biochemistry.

[30]  Meital Reches,et al.  Designed aromatic homo-dipeptides: formation of ordered nanostructures and potential nanotechnological applications , 2006, Physical Biology.

[31]  C. Ionescu-Zanetti,et al.  Surface-catalyzed Amyloid Fibril Formation* , 2002, The Journal of Biological Chemistry.

[32]  Z. Barkay,et al.  Structural transition in peptide nanotubes. , 2011, Biomacromolecules.

[33]  Chiu Fan Lee,et al.  Elongation dynamics of amyloid fibrils: a rugged energy landscape picture. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[34]  Ehud Gazit,et al.  Elementary building blocks of self-assembled peptide nanotubes. , 2010, Journal of the American Chemical Society.

[35]  C. Tatko,et al.  Selective Aromatic Interactions in β-Hairpin Peptides , 2002 .

[36]  Satoshi Takahashi,et al.  Direct Observation of Aβ Amyloid Fibril Growth and Inhibition , 2004 .

[37]  R. Hochstrasser,et al.  2D IR provides evidence for mobile water molecules in β-amyloid fibrils , 2009, Proceedings of the National Academy of Sciences.

[38]  S. Santini,et al.  Pathway Complexity of Alzheimer's β-Amyloid Aβ16-22 Peptide Assembly , 2004 .

[39]  S. Müller,et al.  Multiple assembly pathways underlie amyloid-beta fibril polymorphisms. , 2005, Journal of molecular biology.

[40]  D. Thirumalai,et al.  Dissecting the assembly of A β 16-22 amyloid peptides into antiparallel β-sheets , 2002 .

[41]  Ehud Gazit,et al.  A possible role for π‐stacking in the self‐assembly of amyloid fibrils , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  Carl Henrik Görbitz,et al.  The structure of nanotubes formed by diphenylalanine, the core recognition motif of Alzheimer's beta-amyloid polypeptide. , 2006, Chemical communications.

[43]  P. Derreumaux,et al.  Targeting the early steps of Aβ16–22 protofibril disassembly by N‐methylated inhibitors: A numerical study , 2009, Proteins.

[44]  Ulf Reimer,et al.  Barriers to Rotation of Secondary Amide Peptide Bonds , 1998 .

[45]  E. Gazit,et al.  A model for the role of short self‐assembled peptides in the very early stages of the origin of life , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[46]  D. Kirschner,et al.  Structural analysis of Alzheimer's beta(1-40) amyloid: protofilament assembly of tubular fibrils. , 1998, Biophysical journal.

[47]  The impact of ionic liquids on amyloid fibrilization of Aβ16-22: tuning the rate of fibrilization using a reverse Hofmeister strategy. , 2011, Physical chemistry chemical physics : PCCP.

[48]  David Eisenberg,et al.  Molecular basis for amyloid-β polymorphism , 2011, Proceedings of the National Academy of Sciences.

[49]  U. Aebi,et al.  Watching amyloid fibrils grow by time-lapse atomic force microscopy. , 1999, Journal of molecular biology.

[50]  R. Wetzel,et al.  Abeta(1-40) forms five distinct amyloid structures whose beta-sheet contents and fibril stabilities are correlated. , 2010, Journal of molecular biology.

[51]  Michele Vendruscolo,et al.  Role of Intermolecular Forces in Defining Material Properties of Protein Nanofibrils , 2007, Science.

[52]  B. Nilsson,et al.  Probing aromatic, hydrophobic, and steric effects on the self-assembly of an amyloid-β fragment peptide. , 2011, Molecular bioSystems.

[53]  Richard D. Leapman,et al.  Self-Propagating, Molecular-Level Polymorphism in Alzheimer's ß-Amyloid Fibrils , 2005, Science.

[54]  Alessandro Laio,et al.  Stability and structure of oligomers of the Alzheimer peptide Abeta16-22: from the dimer to the 32-mer. , 2006, Biophysical journal.

[55]  D. Walsh,et al.  Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. , 1997, The Journal of biological chemistry.

[56]  Yan Liang,et al.  Direct observation of nucleation and growth in amyloid self-assembly. , 2010, Journal of the American Chemical Society.

[57]  L. Adler-Abramovich,et al.  Thermal and chemical stability of diphenylalanine peptide nanotubes: implications for nanotechnological applications. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[58]  V. Conticello,et al.  Macroscale assembly of peptide nanotubes. , 2007, Chemical communications.

[59]  A. Oleinikova,et al.  Thermal expansivity of amyloid beta(16-22) peptides and their aggregates in water. , 2009, Physical chemistry chemical physics : PCCP.

[60]  D. Selkoe,et al.  Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide , 2007, Nature Reviews Molecular Cell Biology.

[61]  K. Kjaer,et al.  Amyloid-beta fibrillogenesis seeded by interface-induced peptide misfolding and self-assembly. , 2010, Biophysical journal.

[62]  R. Leapman,et al.  A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[63]  B. Nilsson,et al.  Clarifying the influence of core amino acid hydrophobicity, secondary structure propensity, and molecular volume on amyloid-β 16-22 self-assembly. , 2011, Molecular bioSystems.

[64]  Yundong Wu,et al.  Molecular dynamics studies of hexamers of amyloid‐β peptide (16–35) and its mutants: Influence of charge states on amyloid formation , 2006, Proteins.

[65]  Joan-Emma Shea,et al.  Effect of beta-sheet propensity on peptide aggregation. , 2009, The Journal of chemical physics.

[66]  T. Morgan,et al.  Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[67]  E. Gazit,et al.  Controlled patterning of aligned self-assembled peptide nanotubes , 2006, Nature nanotechnology.

[68]  M. Kirkitadze,et al.  Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[69]  A. Mehta,et al.  Peptides organized as bilayer membranes. , 2010, Angewandte Chemie.