The Kinetics, Thermodynamics and Mechanisms of Short Aromatic Peptide Self-Assembly

  • Thomas O. Mason
  • Alexander K. BuellEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1174)


The self-assembly of short aromatic peptides and peptide derivatives into a variety of different nano- and microstructures (fibrillar gels, crystals, spheres, plates) is a promising route toward the creation of bio-compatible materials with often unexpected and useful properties. Furthermore, such simple self-assembling systems have been proposed as model systems for the self-assembly of longer peptides, a process that can be linked to biological function and malfunction. Much effort has been made in the last 15 years to explore the space of peptide sequences, chemical modifications and solvent conditions in order to maximise the diversity of assembly morphologies and properties. However, quantitative studies of the corresponding mechanisms of, and driving forces for, peptide self-assembly have remained relatively scarce until recently. In this chapter we review the current state of understanding of the thermodynamic driving forces and self-assembly mechanisms of short aromatic peptides into supramolecular structures. We will focus on experimental studies of the assembly process and our perspective will be centered around diphenylalanine (FF), a key motif of the amyloid β sequence and a paradigmatic self-assembly building block. Our main focus is the basic physical chemistry and key structural aspects of such systems, and we will also compare the mechanism of dipeptide aggregation with that of longer peptide sequences into amyloid fibrils, with discussion on how these mechanisms may be revealed through detailed analysis of growth kinetics, thermodynamics and other fundamental properties of the aggregation process.


FF Aromaticity Amyloid Self-assembly Crystal Fibril Gel Nucleation Microfluidics Biomaterials 



TOM thanks the Newman Foundation and the Weizmann Institute for funding. AKB thanks the Turnberg Foundation for a travel grant to Tel Aviv (2011), that enabled to start the mechanistic studies of short aromatic peptide self-assembly.


  1. 1.
    Waugh DF (1944) The linkage of corpuscular protein molecules. I. A fibrous modification of insulin. J Am Chem Soc 66:663–663Google Scholar
  2. 2.
    Kendrew JC, Bodo G, Dintzis HM, Parrish R, Wyckoff H, Phillips DC (1958) A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 181:662–666PubMedCrossRefGoogle Scholar
  3. 3.
    Kidd M (1963) Paired helical filaments in electron microscopy of Alzheimers disease. Nature 197:192–193PubMedCrossRefGoogle Scholar
  4. 4.
    Dobson CM (2003) Protein folding and misfolding. Nature 426:884–890PubMedCrossRefGoogle Scholar
  5. 5.
    Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CC (1997) Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol 273:729–739CrossRefGoogle Scholar
  6. 6.
    Polverino de Laureto P, Taddei N, Frare E, Capanni C, Costantini S, Zurdo J, Chiti F, Dobson CM, Fontana A (2003) Protein aggregation and amyloid fibril formation by an SH3 domain probed by limited proteolysis. J Mol Biol 334:129–141PubMedCrossRefGoogle Scholar
  7. 7.
    Nelson R, Sawaya MR, Balbirnie M, Madsen A, Riekel C, Grothe R, Eisenberg D (2005) Structure of the cross-beta spine of amyloid-like fibrils. Nature 435:773–778PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Colvin MT, Silvers R, Frohm B, Su Y, Linse S, Griffin RG (2015) High resolution structural characterization of Aβ42 amyloid fibrils by magic angle spinning NMR. J Am Chem Soc 137:7509–7518PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Gremer L, Schölzel D, Schenk C, Reinartz E, Labahn J, Ravelli RBG, Tusche M, Lopez-Iglesias C, Hoyer W, Heise H, Willbold D, Schröder GF (2017) Fibril structure of amyloid-β(1–42) by cryo-electron microscopy. Science 358:116–119PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Fitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ, Crowther RA, Ghetti B, Goedert M, Scheres SHW (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547:185–190PubMedPubMedCentralGoogle Scholar
  11. 11.
    Azriel R, Gazit E (2001) Analysis of the minimal amyloid-forming fragment of the islet amyloid polypeptide. An experimental support for the key role of the phenylalanine residue in amyloid formation. J Biol Chem 276:34156–34161PubMedGoogle Scholar
  12. 12.
    Reches M, Gazit E (2003) Casting metal nanowires within discrete self-assembled peptide nanotubes. Science 300:625–627PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and down syndrome. Proc Natl Acad Sci U S A 82:4245–4249PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Görbitz CH (2001) Nanotube formation by hydrophobic dipeptides. Chemistry 7:5153–5159PubMedCrossRefGoogle Scholar
  15. 15.
    Yemini M, Reches M, Gazit E, Rishpon (2005) Peptide nanotube-modified electrodes for enzyme-biosensor applications. J Anal Chem 77:5155–5159PubMedCrossRefGoogle Scholar
  16. 16.
    Kol N, Adler-Abramovich L, Barlam D, Shneck RZ, Gazit E, Rousso I (2005) Selfassembled peptide nanotubes are uniquely rigid bioinspired supramolecular structures. Nano Lett 5:1343–1346CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kholkin A, Amdursky N, Bdikin I, Gazit E, Rosenman G (2010) Strong piezoelectricity in bioinspired peptide nanotubes. ACS Nano 4:610–614PubMedCrossRefGoogle Scholar
  18. 18.
    Wang M, Xiong S, Wu X, Chu PK (2011) Effects of water molecules on photoluminescence from hierarchical peptide nanotubes and water probing capability. Small 7:2801–2807PubMedCrossRefGoogle Scholar
  19. 19.
    Mitra RN, Das D, Roy S, Das PK (2007) Structure and properties of low molecular weight amphiphilic peptide hydrogelators. J Phys Chem B 111:14107–14113PubMedCrossRefGoogle Scholar
  20. 20.
    Smith AM, Williams RJ, Tang C, Coppo P, Collins RF, Turner ML, Saiani A, Ulijn RV (2008) Fmoc-Diphenylalanine self assembles to a hydrogel via a novel architecture based on ππ interlocked β-sheets. Adv Mater 20:37–41CrossRefGoogle Scholar
  21. 21.
    Johnson EK, Adams DJ, Cameron PJ (2011) Peptide based low molecular weight gelators. J Mater Chem 21:2024–2027CrossRefGoogle Scholar
  22. 22.
    Whitesides G, Mathias J, Seto C (1991) Molecular self-assembly and nanochemistry: a chemical strategy for the synthesis of nanostructures. Science 254:1312–1319CrossRefGoogle Scholar
  23. 23.
    Whitesides GM, Grzybowski B (2002) Self-assembly at all scales. Science 295:2418–2421PubMedCrossRefGoogle Scholar
  24. 24.
    Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637PubMedCrossRefGoogle Scholar
  25. 25.
    Frishman D, Argos P (1995) Knowledge-based protein secondary structure assignment. Proteins Struct Funct Bioinf 23:566–579CrossRefGoogle Scholar
  26. 26.
    Perrin CL, Nielson JB (1997) Strong hydrogen bonds in chemistry and biology. Annu Rev Phys Chem 48:511–544PubMedCrossRefGoogle Scholar
  27. 27.
    Steiner T (2002) The hydrogen bond in the solid state. Angew Chem Int Ed 41:48–76CrossRefGoogle Scholar
  28. 28.
    Wang J, Liu K, Xing R, Yan X (2016) Peptide self-assembly: thermodynamics and kinetics. Chem Soc Rev 45:5589–5604PubMedCrossRefGoogle Scholar
  29. 29.
    Bowie JU (2011) Membrane protein folding: how important are hydrogen bonds? Curr Opin Struct Biol 21:42–49PubMedCrossRefGoogle Scholar
  30. 30.
    Sheu S-Y, Yang D-Y, Selzle H, Schlag E (2003) Energetics of hydrogen bonds in peptides. Proc Natl Acad Sci 100:12683–12687PubMedCrossRefGoogle Scholar
  31. 31.
    Grzybowski BA, Ishchenko AV, DeWitte RS, Whitesides GM, Shakhnovich EI (2000) Development of a knowledge-based potential for crystals of small organic molecules: calculation of energy surfaces for C=O⋅HN hydrogen bonds. J Phys Chem B 104:7293–7298CrossRefGoogle Scholar
  32. 32.
    Stone A (2013) The theory of intermolecular forces. Oxford University Press, OxfordCrossRefGoogle Scholar
  33. 33.
    Gazit E (2007) Self-assembled peptide nanostructures: the design of molecular building blocks and their technological utilization. Chem Soc Rev 36:1263–1269PubMedCrossRefGoogle Scholar
  34. 34.
    Holmes TC, de Lacalle S, Su X, Liu G, Rich A, Zhang S (2000) Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. Proc Natl Acad Sci U S A 97:6728–6733PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Caplan MR, Schwartzfarb EM, Zhang S, Kamm RD, Lauffenburger DA (2002) Control of self-assembling oligopeptide matrix formation through systematic variation of amino acid sequence. Biomaterials 23:219–227PubMedCrossRefGoogle Scholar
  36. 36.
    McDonald IK, Thornton JM (1994) Satisfying hydrogen bonding potential in proteins. J Mol Biol 238:777–793PubMedCrossRefGoogle Scholar
  37. 37.
    Kroon J, Kanters J (1974) Non-linearity of hydrogen bonds in molecular crystals. Nature 248:667CrossRefGoogle Scholar
  38. 38.
    Allen FH, Bird CM, Rowland RS, Raithby PR (1997) Hydrogen-bond acceptor and donor properties of divalent sulfur (Y-S-Z and R-S-H). Acta Crystallogr B Struct Sci Cryst Eng Mater 53:696–701CrossRefGoogle Scholar
  39. 39.
    Sarkhel S, Desiraju GR (2004) N-H⋯O, O-H⋯O, and C-H⋯O hydrogen bonds in protein–ligand complexes: strong and weak interactions in molecular recognition. Proteins Struct Funct Bioinf 54:247–259CrossRefGoogle Scholar
  40. 40.
    Pogorelyi VK (1977) Weak hydrogen bonds. Russ Chem Rev 46:316–336CrossRefGoogle Scholar
  41. 41.
    Desiraju GR (1991) Hydration in organic crystals: prediction from molecular structure. J Chem Soc Chem Commun 6:426–428CrossRefGoogle Scholar
  42. 42.
    Derewenda ZS, Lee L, Derewenda U (1995) The occurrence of C–H··· O hydrogen bonds in proteins. J Mol Biol 252:248–262PubMedCrossRefGoogle Scholar
  43. 43.
    Perutz M (1993) The role of aromatic rings as hydrogen-bond acceptors in molecular recognition. Phil Trans R Soc A 345:105–112CrossRefGoogle Scholar
  44. 44.
    Kauzmann W (1959) Some factors in the interpretation of protein denaturation. In: Anfinsen C, Anson M, Bailey K, Edsall JT (Eds) Advances in protein chemistry, vol 14. Academic, New York, pp 1–63Google Scholar
  45. 45.
    Tanford C (1978) The hydrophobic effect and the organization of living matter. Science 200:1012–1018PubMedCrossRefGoogle Scholar
  46. 46.
    Pratt LR, Chandler D (1977) Theory of the hydrophobic effect. J Chem Phys 67:3683–3704CrossRefGoogle Scholar
  47. 47.
    Pratt LR, Chandler D (1980) Hydrophobic solvation of nonspherical solutes. J Chem Phys 73:3430–3433CrossRefGoogle Scholar
  48. 48.
    Stillinger FH (1973) In: Kay RL (ed) Structure in aqueous solutions of nonpolar solutes from the standpoint of scaled-particle theory. The physical chemistry of aqueous system: a symposium in honor of Henry S. Frank on his seventieth birthday. Springer US, Boston, pp 43–60Google Scholar
  49. 49.
    Lum K, Chandler D, Weeks JD (1999) Hydrophobicity at small and large length scales. J Phys Chem B 103:4570–4577CrossRefGoogle Scholar
  50. 50.
    Huang DM, Chandler D (2002) The hydrophobic effect and the influence of solute-solvent attractions. J Phys Chem B 106:2047–2053CrossRefGoogle Scholar
  51. 51.
    Huang DM, Geissler PL, Chandler D (2001) Scaling of hydrophobic solvation free energies. J Phys Chem B 105:6704–6709CrossRefGoogle Scholar
  52. 52.
    Chandler D (2005) Interfaces and the driving force of hydrophobic assembly. Nature 437:640–647PubMedCrossRefGoogle Scholar
  53. 53.
    Patterson D, Barbe M (1976) Enthalpy-entropy compensation and order in alkane and aqueous systems. J Phys Chem 80:2435–2436CrossRefGoogle Scholar
  54. 54.
    Shinoda K, Fujihira M (1968) The analysis of the solubility of hydrocarbons in water. Bull Chem Soc Jpn 41:2612–2615CrossRefGoogle Scholar
  55. 55.
    Fine RA, Millero FJJ (1973) Compressibility of water as a function of temperature and pressure. Chem Phys 59:5529–5536Google Scholar
  56. 56.
    Garde S, Hummer G, García AE, Paulaitis ME, Pratt LR (1996) Origin of entropy convergence in hydrophobic hydration and protein folding. Phys Rev Lett 77:4966PubMedCrossRefGoogle Scholar
  57. 57.
    Raschke TM, Tsai J, Levitt M (2001) Quantification of the hydrophobic interaction by simulations of the aggregation of small hydrophobic solutes in water. Proc Natl Acad Sci U S A 98:5965–5969PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Dill KA (1985) Theory for the folding and stability of globular proteins. Biochemistry 24:1501–1509PubMedCrossRefGoogle Scholar
  59. 59.
    Agashe VR, Shastry M, Udgaonkar JB (1995) Initial hydrophobic collapse in the folding of barstar. Nature 377:754PubMedCrossRefGoogle Scholar
  60. 60.
    Richards FM (1977) Areas, volumes, packing and protein structure. Annu Rev Biophys Bioeng 6:151–176PubMedCrossRefGoogle Scholar
  61. 61.
    Görbitz CH (2010) Structures of dipeptides: the head-to-tail story. Acta Crystallogr B 66:84–93PubMedCrossRefGoogle Scholar
  62. 62.
    Samanta U, Pal D, Chakrabarti P (1999) Packing of aromatic rings against tryptophan residues in proteins. Acta Crystallogr D Biol Crystallogr 55:1421–1427PubMedCrossRefGoogle Scholar
  63. 63.
    Chakrabarti P, Bhattacharyya R (2007) Geometry of nonbonded interactions involving planar groups in proteins. Prog Biophys Mol Biol 95:83–137PubMedCrossRefGoogle Scholar
  64. 64.
    Chourasia M, Sastry GM, Sastry, GN (2011) Aromatic-aromatic interactions database, A2ID: an analysis of aromatic networks in proteins. Int J Biol Macromol 48:540–552PubMedCrossRefGoogle Scholar
  65. 65.
    Thomas A, Meurisse R, Brasseur R (2002) Aromatic side-chain interactions in proteins. II. Near- and far-sequence Phe-X pairs. Proteins 48:635–644PubMedGoogle Scholar
  66. 66.
    Hobza P, Selzle HL, Schlag EW (1996) Potential energy surface for the Benzene Dimer. Results of ab initio CCSD(T) calculations show two nearly isoenergetic structures: T-shaped and parallel-displaced. J Phys Chem 100:18790–18794CrossRefGoogle Scholar
  67. 67.
    Ninkovic DB, Andric JM, Malkov SN, Zaric SD (2014) What are the preferred horizontal displacements of aromatic-aromatic interactions in proteins? Comparison with the calculated benzene-benzene potential energy surface. Phys Chem Chem Phys 16:11173–11177PubMedCrossRefGoogle Scholar
  68. 68.
    McGaughey GB, Gagné M, Rappé AK (1998) pi-Stacking interactions. Alive and well in proteins. J Biol Chem 273:15458–15463PubMedCrossRefGoogle Scholar
  69. 69.
    Street AG, Mayo SL (1999) Intrinsic β-sheet propensities result from van der Waals interactions between side chains and the local backbone. Proc Natl Acad Sci U S A 96:9074–9076PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Malkov SN, Živković MV; Beljanski MV, Hall MB, Zarić SD (2008) A reexamination of the propensities of amino acids towards a particular secondary structure: classification of amino acids based on their chemical structure. J Mol Model 14:769–775PubMedCrossRefGoogle Scholar
  71. 71.
    Samanta U, Bahadur RP, Chakrabarti P (2002) Quantifying the accessible surface area of protein residues in their local environment. Protein Eng Des Sel 15:659–667CrossRefGoogle Scholar
  72. 72.
    Hunter CA, Singh J, Thornton JM (1991) Pi-pi interactions: the geometry and energetics of phenylalanine-phenylalanine interactions in proteins. J Mol Biol 218:837–846PubMedCrossRefGoogle Scholar
  73. 73.
    Tenidis K, Waldner M, Bernhagen J, Fischle W, Bergmann M, Weber M, Merkle M-L, Voelter W, Brunner H, Kapurniotu A (2000) Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties. J Mol Biol 295:1055–1071PubMedCrossRefGoogle Scholar
  74. 74.
    Tjernberg LO, Näslund J, Lindqvist F, Johansson J, Karlström AR, Thyberg J, Terenius L, Nordstedt C (1996) Arrest of beta-amyloid fibril formation by a pentapeptide ligand. J Biolog Chem 271:8545–8548CrossRefGoogle Scholar
  75. 75.
    Findeis MA, Musso GM, Arico-Muendel CC, Benjamin HW, Hundal AM, Lee, J-J, Chin J, Kelley M, Wakefield J, Hayward NJ, Molineaux SM (1999) Modified-peptide inhibitors of amyloid β-peptide polymerization. Biochemistry (Mosc) 38:6791–6800, PMID: 10346900CrossRefGoogle Scholar
  76. 76.
    Gazit E (2002) A possible role for p-stacking in the self-assembly of amyloid fibrils. FASEB J 16:77–83CrossRefGoogle Scholar
  77. 77.
    Tjernberg L, Hosia W, Bark N, Thyberg J, Johansson J (2002) Charge attraction and beta propensity are necessary for amyloid fibril formation from tetrapeptides. J Biol Chem 277:43243–43246PubMedCrossRefGoogle Scholar
  78. 78.
    Castelletto V, Hamley IW, Cenker C, Olsson U, Adamcik J, Mezzenga R, Miravet JF, Escuder B, Rodriguez-Llansola F (2011) Influence of end-capping on the self-assembly of model amyloid peptide fragments. J Phys Chem B 115:2107–2116PubMedCrossRefGoogle Scholar
  79. 79.
    Lakshmanan A, Cheong DW, Accardo A, Di Fabrizio E, Riekel C, Hauser CA (2013) Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis. Proc Natl Acad Sci U S A 110:519–524PubMedCrossRefGoogle Scholar
  80. 80.
    Genji M, Yano Y, Hoshino M, Matsuzaki K (2017) Aromaticity of phenylalanine residues is essential for amyloid formation by Alzheimer’s amyloid β-peptide. Chem Pharm Bull 65:668–673PubMedCrossRefGoogle Scholar
  81. 81.
    Korn A, Surendran D, Krueger M, Maiti S, Huster D (2018) Ring structure modifications of phenylalanine 19 increase fibrillation kinetics and reduce toxicity of amyloid β (1–40). Chem Commun (Camb) 54:5430–5433CrossRefGoogle Scholar
  82. 82.
    Yan X, Cui Y, He Q, Wang K, Li J (2008) Organogels based on self-assembly of diphenylalanine peptide and their application to immobilize quantum dots. Chem Mater 20:1522–1526CrossRefGoogle Scholar
  83. 83.
    Demirel G, Malvadkar N, Demirel MC (2009) Control of protein adsorption onto core- shell tubular and vesicular structures of diphenylalanine/parylene. Langmuir 26:1460–1463CrossRefGoogle Scholar
  84. 84.
    Su Y, Yan X, Wang A, Fei J, Cui Y, He Q, Li J (2010) A peony-flower-like hierarchical mesocrystal formed by diphenylalanine. J Mater Chem 20:6734–6740CrossRefGoogle Scholar
  85. 85.
    Zhu P, Yan X, Su Y, Yang Y, Li J (2010) Solvent-induced structural transition of self-assembled dipeptide: from organogels to microcrystals. Chem Eur J 16:3176–3183PubMedCrossRefGoogle Scholar
  86. 86.
    Huang R, Qi W, Su R, Zhao J, He Z (2011) Solvent and surface controlled self-assembly of diphenylalanine peptide: from microtubes to nanofibers. Soft Matter 7:6418–6421CrossRefGoogle Scholar
  87. 87.
    Huang R, Wang Y, Qi W, Su R, He Z (2014) Temperature-induced reversible self-assembly of diphenylalanine peptide and the structural transition from organogel to crystalline nanowires. Nanoscale Res Lett 9:653PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Mason TO, Chirgadze DY, Levin A, Adler-Abramovich L, Gazit E, Knowles TPJ, Buell AK (2014) Expanding the solvent chemical space for self-assembly of dipeptide nanostructures. ACS Nano 8:1243–53PubMedCrossRefGoogle Scholar
  89. 89.
    Song Y, Challa SR, Medforth CJ, Qiu Y, Watt RK, Pena D, Miller JE, van Swol F, Shelnutt JA (2004) Synthesis of peptide-nanotube platinum-nanoparticle composites. Chem Commun (Camb) 1044–1045Google Scholar
  90. 90.
    Mason TO, Michaels TCT, Levin A, Dobson CM, Gazit E, Knowles TPJ, Buell AK (2017) Thermodynamics of polypeptide supramolecular assembly in the short-chain limit. J Am Chem Soc 139:16134–16142PubMedCrossRefGoogle Scholar
  91. 91.
    Park JS, Han TH, Oh JK, Kim SO (2010) Capillarity induced large area patterning of peptide nanowires. J Nanosci Nanotech 10:6954–6957CrossRefGoogle Scholar
  92. 92.
    Adams DJ, Butler MF, Frith WJ, Kirkland M, Mullen L, Sanderson P (2009) A new method for maintaining homogeneity during liquid–hydrogel transitions using low molecular weight hydrogelators. Soft Matter 5:1856–1862CrossRefGoogle Scholar
  93. 93.
    Zhang Y, Kuang Y, Gao Y, Xu B (2010) Versatile small-molecule motifs for self-assembly in water and the formation of biofunctional supramolecular hydrogels. Langmuir 27:529–537PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Zhou J, Du X, Gao Y, Shi J, Xu B (2014) Aromatic-aromatic interactions enhance interfiber contacts for enzymatic formation of a spontaneously aligned supramolecular hydrogel. J Am Chem Soc 136:2970–2973PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Debnath S, Roy S, Ulijn RVJ (2013) Peptide nanofibers with dynamic instability through nonequilibrium biocatalytic assembly. Am Chem Soc 135:16789–16792CrossRefGoogle Scholar
  96. 96.
    Mason TO, Michaels TCT, Levin A, Gazit E, Dobson CM, Buell AK, Knowles TPJ (2016) Synthesis of Nonequilibrium Supramolecular Peptide Polymers on a Microfluidic Platform. J Am Chem Soc 138:9589–9596PubMedCrossRefGoogle Scholar
  97. 97.
    Adler-Abramovich L, Aronov D, Beker P, Yevnin M, Stempler S, Buzhansky L, Rosenman G, Gazit E (2009) Self-assembled arrays of peptide nanotubes by vapour deposition. Nat Nanotechnol 4:849PubMedCrossRefGoogle Scholar
  98. 98.
    Bank-Srour B, Becker P, Krasovitsky L, Gladkikh A, Rosenberg Y, Barkay Z, Rosenman G (2013) Physical vapor deposition of peptide nanostructures. Polymer J 45:494CrossRefGoogle Scholar
  99. 99.
    Vasudev MC, Koerner H, Singh KM, Partlow BP, Kaplan DL, Gazit E, Bunning TJ, Naik RR (2014) Vertically aligned peptide nanostructures using plasmaenhanced chemical vapor deposition. Biomacromolecules 15:533–540PubMedCrossRefGoogle Scholar
  100. 100.
    Levin A, Mason TO, Adler-Abramovich L, Buell AK, Meisl G, Galvagnion C, Bram Y, Stratford SA, Dobson CM, Knowles TPJ, Gazit E (2014) Ostwalds rule of stages governs structural transitions and morphology of dipeptide supramolecular polymers. Nat Commun 5:5219PubMedCrossRefGoogle Scholar
  101. 101.
    Adler-Abramovich L, Reches M, Sedman VL, Allen S, Tendler SJB, Gazit E (2006) Thermal and chemical stability of diphenylalanine peptide nanotubes: implications for nanotechnological applications. Langmuir 22:1313–1320PubMedCrossRefGoogle Scholar
  102. 102.
    Sedman VL, Adler-Abramovich L, Allen S, Gazit E, Tendler SJB (2006) Direct observation of the release of phenylalanine from diphenylalanine nanotubes. J Am Chem Soc 128:6903–6908PubMedCrossRefGoogle Scholar
  103. 103.
    Tamamis P, Adler-Abramovich L, Reches M, Marshall K, Sikorski P, Serpell L, Gazit E, Archontis G (2009) Self-assembly of phenylalanine oligopeptides: insights from experiments and simulations. Biophys J 96:5020–5029PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Adler-Abramovich L, Kol N, Yanai I, Barlam D, Shneck RZ, Gazit E, Rousso I (2010) Self-assembled organic nanostructures with metallic-like stiffness. Angew Chem Int Ed Engl 49:9939–9942PubMedCrossRefGoogle Scholar
  105. 105.
    Chen L, Morris K, Laybourn A, Elias D, Hicks MR, Rodger A, Serpell L, Adams DJ (2010) Self-assembly mechanism for a naphthalene-dipeptide leading to hydrogelation. Langmuir 26:5232–5242PubMedCrossRefGoogle Scholar
  106. 106.
    Fichman G, Guterman T, Damron J, Adler-Abramovich L, Schmidt J, Kesselman E, Shimon LJ, Ramamoorthy A, Talmon Y, Gazit E (2016) Spontaneous structural transition and crystal formation in minimal supramolecular polymer model. Sci Adv 2:e1500827PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Cardoso AZ, Mears LLE, Cattoz BN, Griffiths PC, Schweins R, Adams DJ (2016) Linking micellar structures to hydrogelation for salt-triggered dipeptide gelators. Soft Matter 12:3612–3621PubMedCrossRefGoogle Scholar
  108. 108.
    Onogi S, Shigemitsu H, Yoshii T, Tanida T, Ikeda M, Kubota R, Hamachi I (2016) In situ real-time imaging of self-sorted supramolecular nanofibres. Nat Chem 8:743–752PubMedCrossRefGoogle Scholar
  109. 109.
    Kubota R, Liu S, Shigemitsu H, Nakamura K, Tanaka W, Ikeda M, Hamachi I (2018) Imaging-based study on control factors over self-sorting of supramolecular nanofibers formed from peptide-and lipid-type hydrogelators. Bioconjug Chem 29(6):2058–2067PubMedCrossRefGoogle Scholar
  110. 110.
    Tena-Solsona M, Escuder B, Miravet JF, Casttelleto V, Hamley IW, Dehsorkhi A (2015) Thermodynamic and kinetic study of the fibrillization of a family of tetrapeptides and its application to self-sorting. What takes so long? Chem Mater 27:3358–3365CrossRefGoogle Scholar
  111. 111.
    Yan X, He Q, Wang K, Duan L, Cui Y, Li J (2007) Transition of cationic dipeptide nanotubes into vesicles and oligonucleotide delivery. Angew Chem Int Ed Engl 119:2483–2486CrossRefGoogle Scholar
  112. 112.
    Wallace M, Iggo JA, Adams DJ (2015) Using solution state NMR spectroscopy to probe NMR invisible gelators. Soft Matter 11:7739–7747PubMedCrossRefGoogle Scholar
  113. 113.
    Wallace M, Iggo JA, Adams DJ (2017) Probing the surface chemistry of self-assembled peptide hydrogels using solution-state NMR spectroscopy. Soft Matter 13:1716–1727PubMedCrossRefGoogle Scholar
  114. 114.
    Do TD, Bowers MT (2015) Diphenylalanine self assembly: novel ion mobility methods showing the essential role of water. Anal Chem 87:4245–4252PubMedCrossRefGoogle Scholar
  115. 115.
    Chen L, Pont G, Morris K, Lotze G, Squires A, Serpell LC, Adams DJ (2011) Salt-induced hydrogelation of functionalised-dipeptides at high pH. Chem Commun 47:12071–12073CrossRefGoogle Scholar
  116. 116.
    Martin AD, Wojciechowski JP, Robinson AB, Heu C, Garvey CJ, Ratcliffe J, Waddington LJ, Gardiner J, Thordarson P (2017) Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups. Sci Rep 7:43947PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Colquhoun C, Draper ER, Schweins R, Marcello M, Vadukul D, Serpell LC, Adams DJ (2017) Controlling the network type in self-assembled dipeptide hydrogels. Soft Matter 13:1914–1919PubMedCrossRefGoogle Scholar
  118. 118.
    Shigemitsu H, Fujisaku T, Tanaka W, Kubota R, Minami S, Urayama K, Hamachi I (2018) An adaptive supramolecular hydrogel comprising self-sorting double nanofibre networks. Nat Nanotechnol 1(13):165–172CrossRefGoogle Scholar
  119. 119.
    Arnon ZA, Vitalis A, Levin A, Michaels TC, Caflisch A, Knowles TP, Adler-Abramovich L, Gazit E (2016) Dynamic microfluidic control of supramolecular peptide self-assembly. Nat Commun 7:13190PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Amdursky N, Beker P, Koren I, Bank-Srour B, Mishina E, Semin S, Rasing T, Rosenberg Y, Barkay Z, Gazit E, Rosenman G (2011) Structural transition in peptide nanotubes. Biomacromolecules 12:1349–1354PubMedCrossRefGoogle Scholar
  121. 121.
    Handelman A, Natan A, Rosenman G (2014) Structural and optical properties of short peptides: nanotubes-to-nanofibers phase transformation. J Pept Sci 20:487–493PubMedCrossRefGoogle Scholar
  122. 122.
    Ryu J, Park CB (2008) Solid-phase growth of nanostructures from amorphous peptide thin film: effect of water activity and temperature. Chem Mater 20:4284–4290CrossRefGoogle Scholar
  123. 123.
    Kleinsmann AJ, Nachtsheim BJ (2013) Phenylalanine-containing cyclic dipeptides–the lowest molecular weight hydrogelators based on unmodified proteinogenic amino acids. Chem Commun 49:7818–7820CrossRefGoogle Scholar
  124. 124.
    Zhou X, Fan J, Li N, Du Z, Ying H, Wu J, Xiong J, Bai J (2012) Solubility of l-phenylalanine in water and different binary mixtures from 288.15 to 318.15 K. Fluid Phase Equilibria 316:26–33CrossRefGoogle Scholar
  125. 125.
    Franks F, Gent M, Johnson H (1963) 505. The solubility of benzene in water. J Chem Soc (Resumed) 2716–2723Google Scholar
  126. 126.
    Baldwin RL (1986) Temperature dependence of the hydrophobic interaction in protein folding. Proc Natl Acad Sci U S A 83:8069–8072PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Han TH, Oh JK, Lee G-J, Pyun S-I, Kim SO (2010) Hierarchical assembly of diphenylalanine into dendritic nanoarchitectures. Colloids Surf B Biointerfaces 79:440–445PubMedCrossRefGoogle Scholar
  128. 128.
    McDevit W, Long F (1952) The activity coefficient of benzene in aqueous salt solutions. J Am Chem Soc 74:1773–1777CrossRefGoogle Scholar
  129. 129.
    Marshall KE, Hicks MR, Williams TL, Hoffmann SRVN, Rodger A, Dafforn TR, Serpell LC (2010) Characterizing the assembly of the Sup35 yeast prion fragment, GNNQQNY: structural changes accompany a fiber-to-crystal switch. Biophys J 98:330–338PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Reynolds NP, Adamcik J, Berryman JT, Handschin S, Zanjani AAH, Li W, Liu K, Zhang A, Mezzenga R (2017) Competition between crystal and fibril formation in molecular mutations of amyloidogenic peptides. Nat Commun 8:1338PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Chen L, Revel S, Morris K, C Serpell L, Adams DJ (2010) Effect of molecular structure on the properties of naphthalene- dipeptide hydrogelators. Langmuir 26:13466–13471PubMedCrossRefGoogle Scholar
  132. 132.
    Fleming S, Debnath S, Frederix PW, Tuttle T, Ulijn RV (2013) Aromatic peptide amphiphiles: significance of the Fmoc moiety. Chem Commun 49:10587–10589CrossRefGoogle Scholar
  133. 133.
    Reches M, Gazit E (2005) Self-assembly of peptide nanotubes and amyloid-like structures by charged-termini-capped diphenylalanine peptide analogues. Isr J Chem 45:363–371CrossRefGoogle Scholar
  134. 134.
    Tang C, Ulijn RV, Saiani A (2011) Effect of glycine substitution on Fmocdiphenylalanine self-assembly and gelation properties. Langmuir 27:14438–14449PubMedCrossRefGoogle Scholar
  135. 135.
    Houton KA, Morris KL, Chen L, Schmidtmann M, Jones JTA, Serpell LC, Lloyd GO, Adams DJ (2012) On crystal versus fiber formation in dipeptide hydrogelator systems. Langmuir 28:9797–9806PubMedCrossRefGoogle Scholar
  136. 136.
    Tang C, Smith AM, Collins RF, Ulijn RV, Saiani A (2009) Fmoc-diphenylalanine self-assembly mechanism induces apparent p K a shifts. Langmuir 25:9447–9453PubMedCrossRefGoogle Scholar
  137. 137.
    Ramos Sasselli I, Halling PJ, Ulijn RV, Tuttle T (2016) Supramolecular fibers in gels can be at thermodynamic equilibrium: a simple packing model reveals preferential fibril formation versus crystallization. ACS Nano 10:2661–2668CrossRefGoogle Scholar
  138. 138.
    Hsu S-M, Lin Y-C, Chang J-W, Liu Y-H, Lin H-C (2014) Intramolecular interactions of a phenyl/perfluorophenyl pair in the formation of supramolecular nanofibers and hydrogels. Angew Chem Intl Ed Engl 53:1921–1927CrossRefGoogle Scholar
  139. 139.
    Rajbhandary A, Nilsson BL (2017) Investigating the effects of peptoid substitutions in self-assembly of Fmoc-diphenylalanine derivatives. Pept Sci 108:1–11CrossRefGoogle Scholar
  140. 140.
    Brouhard GJ (2015) Dynamic instability 30 years later: complexities in microtubule growth and catastrophe. Mol Biol Cell 26:1207–1210PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Sadownik JW, Leckie J, Ulijn RV (2011) Micelle to fibre biocatalytic supramolecular transformation of an aromatic peptide amphiphile. Chem Commun (Camb) 47:728–730CrossRefGoogle Scholar
  142. 142.
    Frederix PW, Scott GG, Abul-Haija YM, Kalafatovic D, Pappas CG, Javid N, Hunt NT, Ulijn RV, Tuttle T (2015) Exploring the sequence space for (tri-) peptide self-assembly to design and discover new hydrogels. Nat Chem 7:30–7PubMedCrossRefGoogle Scholar
  143. 143.
    Görbitz C, Etter M (1992) Structure of l-phenylalanine l-phenylalaninium formate. Acta Crystallogr C 48:1317–1320PubMedCrossRefGoogle Scholar
  144. 144.
    Zeng G, Liu L, Xia D, Li Q, Xin Z, Wang J, Besenbacher F, Skrydstrup T, Dong M (2014) Transition of chemically modified diphenylalanine peptide assemblies revealed by atomic force microscopy. RSC Adv 4:7516–7520CrossRefGoogle Scholar
  145. 145.
    Korolkov VV, Allen S, Roberts CJ, Tendler SJ (2013) Surface mediated L-phenylalanyl-L-phenylalanine assembly into large dendritic structures. Faraday Discuss 166:257–267PubMedCrossRefGoogle Scholar
  146. 146.
    Yan X, Cui Y, He Q, Wang K, Li J, Mu W, Wang B, Ou-yang Z-C (2008) Reversible transitions between peptide nanotubes and vesicle-like structures including theoretical modeling studies. Chem Eur J 14:5974–5980PubMedCrossRefGoogle Scholar
  147. 147.
    Reches M, Gazit E (2004) Formation of closed-cage nanostructures by self-assembly of aromatic dipeptides. Nano Lett 4:581–585CrossRefGoogle Scholar
  148. 148.
    Nielsen AE (1984) Electrolyte crystal growth mechanisms. J Cryst Growth 67:289–310CrossRefGoogle Scholar
  149. 149.
    Buell AK, Dhulesia A, White DA, Knowles TP, Dobson CM, Welland ME (2012) Detailed analysis of the energy barriers for amyloid fibril growth. Angew Chem Intl Ed Engl 51:5247–5251CrossRefGoogle Scholar
  150. 150.
    Adler-Abramovich L, Marco P, Arnon ZA, Creasey RCG, Michaels TCT, Levin A, Scurr DJ, Roberts CJ, Knowles TPJ, Tendler SJB, Gazit E (2016) Controlling the physical dimensions of peptide nanotubes by supramolecular polymer coassembly. ACS Nano 10:7436–7442PubMedCrossRefGoogle Scholar
  151. 151.
    Creasey RCG, Louzao I, Arnon ZA, Marco P, Adler-Abramovich L, Roberts CJ, Gazit E, Tendler SJB (2016) Disruption of diphenylalanine assembly by a Boc-modified variant. Soft Matter 12:9451–9457PubMedCrossRefGoogle Scholar
  152. 152.
    Buell AK (2017) The Nucleation of protein aggregates-from crystals to amyloid fibrils. Int Rev Cell Mol Biol 329:187–226PubMedCrossRefGoogle Scholar
  153. 153.
    Wang Y, Huang R, Qi W, Xie Y, Wang M, Su R, He Z (2015) Capillary force-driven, hierarchical co-assembly of dandelion-like peptide microstructures. Small 11:2893–2902PubMedCrossRefGoogle Scholar
  154. 154.
    Amdursky N, Molotskii M, Gazit E, Rosenman G (2010) Elementary building blocks of self-assembled peptide nanotubes. J Am Chem Soc 132:15632–15636PubMedCrossRefGoogle Scholar
  155. 155.
    Gebauer D, Kellermeier M, Gale JD, Bergström L, Cölfen H (2014) Pre-nucleation clusters as solute precursors in crystallisation. Chem Soc Rev 43:2348–2371PubMedCrossRefGoogle Scholar
  156. 156.
    Ishikawa M, Busch C, Motzkus M, Martinho H, Buckup T (2017) Two-step kinetic model as self-assembling mechanism for diphenylalanine micro/nanotubes formation. Phys Chem Chem Phys 19:31647–31654PubMedCrossRefGoogle Scholar
  157. 157.
    Buell AK, Galvagnion C, Gaspar R, Sparr E, Vendruscolo M, Knowles TPJ, Linse S, Dobson CM (2014) Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation. Proc Natl Acad Sci U S A 111(21):7671–7676PubMedCrossRefGoogle Scholar
  158. 158.
    Görbitz CH, Hartviksen LM (2008) The monohydrates of the four polar dipeptides L-seryl-L-asparagine, L-seryl-L-tyrosine, L-tryptophanyl-L-serine and L-tyrosyl-L-tryptophan. Acta Crystallogr C 64:171–6CrossRefGoogle Scholar
  159. 159.
    Görbitz CH, Etter MC (1992) Hydrogen bond connectivity patterns and hydrophobic interactions in crystal structures of small, acyclic peptides. Int J Pept Protein Res 39:93–110PubMedCrossRefGoogle Scholar
  160. 160.
    Görbitz CH (2002) Turns, water cage formation and hydrogen bonding in the structures of l-valyl-l-phenylalanine. Acta Crystallogr B Struct Sci Cryst Eng Mater 58:512–518CrossRefGoogle Scholar
  161. 161.
    Emge TJ, Agrawal A, Dalessio JP, Dukovic G, Inghrim JA, Janjua K, Macaluso M, Robertson LL, Stiglic TJ, Volovik Y, Georgiadis MM (2000) Alaninyltryptophan hydrate, glycyltryptophan dihydrate and tryptophylglycine hydrate. Acta Crystallogr C Cryst Struct Commun 56:e469–e471CrossRefGoogle Scholar
  162. 162.
    Görbitz CH, Gundersen E (1996) L-Valyl-L-alanine. Acta Crystallogr C Cryst Struct Commun 52:1764–1767CrossRefGoogle Scholar
  163. 163.
    Sinnokrot MO, Valeev EF, Sherrill CD (2002) Estimates of the ab initio limit for pi-pi interactions: the benzene dimer. J Am Chem Soc 124:10887–10893PubMedCrossRefGoogle Scholar
  164. 164.
    Lee EC, Kim D, Jurecka P, Tarakeshwar P, Hobza P, Kim KS (2007) Understanding of assembly phenomena by aromatic-aromatic interactions: benzene dimer and the substituted systems. J Phys Chem A 111:3446–3457PubMedCrossRefGoogle Scholar
  165. 165.
    Prampolini G, Livotto PR, Cacelli I (2015) Accuracy of quantum mechanically derived force-fields parameterized from dispersion-corrected DFT data: the benzene dimer as a prototype for aromatic interactions. J Chem Theory Comput 11:5182–5196PubMedCrossRefGoogle Scholar
  166. 166.
    Suresh C, Vijayan M (1987) X-ray studies on crystalline complexes involving amino acids and peptides. Part XIV: closed conformation and head-to-tail arrangement in a new crystal form of L-histidine L-aspartate monohydrate. J Biosci 12:13–21Google Scholar
  167. 167.
    Bernstein J, Davis RE, Shimoni L, Chang N-L (1995) Patterns in hydrogen bonding: functionality and graph set analysis in crystals. Angew Chem Int Ed Engl 34:1555–1573CrossRefGoogle Scholar
  168. 168.
    Etter MC, MacDonald JC, Bernstein J (1990) Graph-set analysis of hydrogen-bond patterns in organic crystals. Acta Crystallogr B Struct Sci Cryst Eng Mater 46:256–262CrossRefGoogle Scholar
  169. 169.
    Vargas R, Garza J, Dixon DA, Hay BP (2000) How strong is the CH⋯OC hydrogen bond? J Am Chem Soc 122:4750–4755CrossRefGoogle Scholar
  170. 170.
    Fabiola GF, Krishnaswamy S, Nagarajan V, Pattabhi V (1997) C-H⋯O hydrogen bonds in β-sheets. Acta Crystallogr D Biol Crystallogr 53:316–320PubMedCrossRefGoogle Scholar
  171. 171.
    Akazome M, Ueno Y, Ooiso H, Ogura K (2000) Enantioselective inclusion of methyl phenyl sulfoxides and benzyl methyl sulfoxides by (R)-phenylglycyl-(R)-phenylglycine and the crystal structures of the inclusion cavities. J Org Chem 65:68–76PubMedCrossRefGoogle Scholar
  172. 172.
    Pellach M, Mondal S, Shimon LJ, Adler-Abramovich L, Buzhansky L, Gazit E (2016) Molecular engineering of self-assembling diphenylalanine analogues results in the formation of distinctive microstructures. Chem Mater 28:4341–4348CrossRefGoogle Scholar
  173. 173.
    Eggleston DS, Hodgson DJ (1985) Intramolecular water bridge and a distorted trans peptide bond in the crystal structure of α-L-glutamyl-L-aspartic acid hydrate. Chem Biol Drug Des 26:509–517Google Scholar
  174. 174.
    Reches M, Gazit E (2006) Controlled patterning of aligned self-assembled peptide nanotubes. Nat Nanotechnol 1:195–200CrossRefGoogle Scholar
  175. 175.
    Görbitz CH (2006) The structure of nanotubes formed by diphenylalanine, the core recognition motif of Alzheimer’s beta-amyloid polypeptide. Chem Commun (Camb) 2332–2334Google Scholar
  176. 176.
    Lekprasert B, Korolkov V, Falamas A, Chis V, Roberts CJ, Tendler SJB, Notingher I (2012) Investigations of the supramolecular structure of individual diphenylalanine nano- and microtubes by polarized Raman microspectroscopy. Biomacromolecules 13:2181–2187PubMedCrossRefGoogle Scholar
  177. 177.
    Eddleston MD, Jones W (2009) Formation of tubular crystals of pharmaceutical compounds. Cryst Growth Des 10:365–370CrossRefGoogle Scholar
  178. 178.
    Kim J, Han TH, Kim Y-I, Park JS, Choi J, Churchill DG, Kim SO, Ihee H (2010) Role of water in directing diphenylalanine assembly into nanotubes and nanowires. Adv Mater 22:583–587PubMedCrossRefGoogle Scholar
  179. 179.
    Li Q, Jia Y, Dai L, Yang Y, Li J (2015) Controlled rod nanostructured assembly of diphenylalanine and their optical waveguide properties. ACS Nano 9:2689–2695PubMedCrossRefGoogle Scholar
  180. 180.
    Pappas CG, Frederix PW, Mutasa T, Fleming S, Abul-Haija YM, Kelly SM, Gachagan A, Kalafatovic D, Trevino J, Ulijn R, Bai S (2015) Alignment of nanostructured tripeptide gels by directional ultrasonication. Chem Commun 51:8465–8468CrossRefGoogle Scholar
  181. 181.
    Pappas CG, Mutasa T, Frederix PW, Fleming S, Bia S, Debnath S, Kelly SM, Gachagan A, Ulijn RV (2015) Transient supramolecular reconfiguration of peptide nanostructures using ultrasound. Mater Horiz 2:198–202CrossRefGoogle Scholar
  182. 182.
    Moholkar VS, Sable SP, Pandit AB (2000) Mapping the cavitation intensity in an ultrasonic bath using the acoustic emission. AIChE J 46:684–694CrossRefGoogle Scholar
  183. 183.
    Tjernberg LO, Callaway DJ, Tjernberg A, Hahne S, Lilliehöök C, Terenius L, Thyberg J, Nordstedt C (1999) A molecular model of Alzheimer amyloid β-peptide fibril formation. J Biol Chem 274:12619–12625PubMedCrossRefGoogle Scholar
  184. 184.
    Mazor Y, Gilead S, Benhar I, Gazit E (2002) Identification and characterization of a novel molecular-recognition and self-assembly domain within the islet amyloid polypeptide. J Mol Biol 322:1013–1024PubMedCrossRefGoogle Scholar
  185. 185.
    Gazit E (2005) Mechanisms of amyloid fibril self-assembly and inhibition. Model short peptides as a key research tool. FEBS J 272:5971–5978PubMedCrossRefGoogle Scholar
  186. 186.
    Jahn TR, Makin OS, Morris KL, Marshall KE, Tian P, Sikorski P, Serpell LC (2010) The common architecture of cross-β amyloid. J Mol Biol 395:717–727PubMedCrossRefGoogle Scholar
  187. 187.
    Carugo O, Djinović-Carugo K (2013) Half a century of Ramachandran plots. Acta Crystallogr D Biol Crystallogr 69:1333–1341PubMedCrossRefGoogle Scholar
  188. 188.
    Hollingsworth SA, Karplus PA (2010) A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. Biomol Concepts 1:271–283PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242PubMedPubMedCentralCrossRefGoogle Scholar
  190. 190.
    Schrödinger LLC (2015) The PyMOL Molecular Graphics System, Version 2.1.0Google Scholar
  191. 191.
    Di Maro S et al (2016) Exploring the N-terminal region of C-X-C motif chemokine 12 (CXCL12): identification of plasma-stable cyclic peptides as novel, potent C-X-C chemokine receptor type 4 (CXCR4) antagonists. J Med Chem 59:8369–8380, PMID: 27571038PubMedCrossRefGoogle Scholar
  192. 192.
    Colletier J-P, Laganowsky A, Landau M, Zhao M, Soriaga AB, Goldschmidt L, Flot D, Cascio D, Sawaya MR, Eisenberg D (2011) Molecular basis for amyloid-β polymorphism. Proc Natl Acad Sci U S A 108:16938–16943PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Spencer RK, Li H, Nowick JS (2014) X-ray crystallographic structures of trimers and higher-order oligomeric assemblies of a peptide derived from Aβ 17–36. J Am Chem Soc 136:5595–5598PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Kreutzer AG, Hamza IL, Spencer RK, Nowick JS (2016) X-ray crystallographic structures of a trimer, dodecamer, and annular pore formed by an Aβ17–36 β-hairpin. J Am Chem Soc 138:4634–4642, PMID: 26967810PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Wälti MA, Ravotti F, Arai H, Glabe CG, Wall JS, Böckmann A, Güntert P, Meier BH, Riek R (2016) Atomic-resolution structure of a disease-relevant Aβ (1–42) amyloid fibril. Proc Natl Acad Sci U S A 113:E4976–E4984PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Perutz MF, Finch JT, Berriman J, Lesk A (2002) Amyloid fibers are water-filled nanotubes. Proc Natl Acad Sci U S A 99:5591–5595PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Sikorski P, Atkins E (2005) New model for crystalline polyglutamine assemblies and their connection with amyloid fibrils. Biomacromolecules 6:425–432PubMedCrossRefGoogle Scholar
  198. 198.
    Buchanan LE, Carr JK, Fluitt AM, Hoganson AJ, Moran SD, de Pablo JJ, Skinner JL, Zanni MT (2014) Structural motif of polyglutamine amyloid fibrils discerned with mixed-isotope infrared spectroscopy. Proc Natl Acad Sci 111:5796–5801PubMedCrossRefGoogle Scholar
  199. 199.
    Makin OS, Serpell LC (2005) Structures for amyloid fibrils. FEBS J 272:5950–5961CrossRefGoogle Scholar
  200. 200.
    Harper JD, Lieber CM, Lansbury PT (1997) Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer’s disease amyloid-β protein. Chem Biol 4:951–959PubMedCrossRefGoogle Scholar
  201. 201.
    Chothia C (1973) Conformation of twisted β-pleated sheets in proteins. J Mol Biol 75:295–302PubMedCrossRefGoogle Scholar
  202. 202.
    Aggeli A, Nyrkova IA, Bell M, Harding R, Carrick L, McLeish TC, Semenov AN, Boden N (2001) Hierarchical self-assembly of chiral rod-like molecules as a model for peptide β-sheet tapes, ribbons, fibrils, and fibers. Proc Natl Acad Sci USA 98:11857–11862PubMedCrossRefGoogle Scholar
  203. 203.
    Usov I, Adamcik J, Mezzenga R (2013) Polymorphism complexity and handedness inversion in serum albumin amyloid fibrils. ACS Nano 7:10465–10474PubMedCrossRefGoogle Scholar
  204. 204.
    Wang S-T, Lin Y, Spencer RK, Thomas MR, Nguyen AI, Amdursky N, Pashuck ET, Skaalure SC, Song CY, Parmar PA, Morgan RM, Ercius P, Aloni S, Zuckermann RN, Stevens MM (2017) Sequence-dependent self-assembly and structural diversity of Islet amyloid polypeptide-derived β-sheet fibrils. ACS Nano 11:8579–8589, PMID: 28771324PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Knowles TPJ, Simone AD, Fitzpatrick AW, Baldwin A, Meehan S, Rajah L, Vendruscolo M, Welland ME, Dobson CM, Terentjev EM (2012) Twisting transition between crystalline and fibrillar phases of aggregated peptides. Phys Rev Lett 109:158101PubMedCrossRefGoogle Scholar
  206. 206.
    Knowles TP, Smith JF, Craig A, Dobson CM, Welland ME (2006) Spatial persistence of angular correlations in amyloid fibrils. Phys Rev Lett 96:238301PubMedCrossRefGoogle Scholar
  207. 207.
    Šarić, A.; Buell AK, Meisl G, Michaels TC, Dobson CM, Linse S, Knowles TP, Frenkel D Physical determinants of the self-replication of protein fibrils. (2016) Nat Phys 12:874–880PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    Cohen SIA, Cukalevski R, Michaels TCT, Saric A, Törnquist M, Vendruscolo M, Dobson CM, Buell AK, Knowles TPJ, Linse S (2018) Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide. Nat Chem 10:523–531PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Cabriolu R, Auer S (2011) Amyloid fibrillation kinetics: insight from atomistic nucleation theory. J Mol Biol 411:275–285PubMedCrossRefGoogle Scholar
  210. 210.
    Fitzpatrick AWP et al (2013) Atomic structure and hierarchical assembly of a crossβ amyloid fibril. Proc Natl Acad Sci USA 110:5468–5473PubMedCrossRefGoogle Scholar
  211. 211.
    Collins SR, Douglass A, Vale RD, Weissman JS (2004) Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLoS Biol 2:e321PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    Buell AK, Blundell JR, Dobson CM, Welland ME, Terentjev EM, Knowles TPJ (2010) Frequency factors in a landscape model of filamentous protein aggregation. Phys Rev Lett 104:228101PubMedPubMedCentralCrossRefGoogle Scholar
  213. 213.
    Kashchiev D, Auer S (2010) Nucleation of amyloid fibrils. J Chem Phys 132:215101PubMedCrossRefGoogle Scholar
  214. 214.
    Cabriolu R, Kashchiev D, Auer S (2010) Atomistic theory of amyloid fibril nucleation. J Chem Phys 133:12B602PubMedCrossRefGoogle Scholar
  215. 215.
    Balbirnie M, Grothe R, Eisenberg DS (2001) An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated β-sheet structure for amyloid. Proc Natl Acad Sci U S A 98:2375–2380PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA, Apostol MI, Thompson MJ, Balbirnie M, Wiltzius JJW, McFarlane HT, Madsen AØ, Riekel C, Eisenberg D (2007) Atomic structures of amyloid cross-b spines reveal varied steric zippers. Nature 447:453 EPCrossRefGoogle Scholar
  217. 217.
    Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE (1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90:549–558PubMedCrossRefGoogle Scholar
  218. 218.
    Han H, Weinreb PH, Lansbury PT Jr (1995) The core alzheimers peptide NAC forms amyloid fibrils which seed and are seeded by β-amyloid: is NAC a common trigger or target in neurodegenerative disease? Chem Biol 2:163–169PubMedCrossRefGoogle Scholar
  219. 219.
    Rodriguez JA et al (2015) Structure of the toxic core of a-synuclein from invisible crystals. Nature 525:486 EPPubMedPubMedCentralCrossRefGoogle Scholar
  220. 220.
    Colvin MT, Silvers R, Ni QZ, Can TV, Sergeyev I, Rosay M, Donovan KJ, Michael B, Wall J, Linse S, Griffin RG (2016) Atomic resolution structure of monomorphic Aβ42 amyloid fibrils. J Am Chem Soc 138:9663–9674, PMID: 27355699PubMedPubMedCentralCrossRefGoogle Scholar
  221. 221.
    Makhatadze GI, Privalov PL (1993) Contribution of hydration to protein folding thermodynamics: I. The enthalpy of hydration. J Mol Biol 232:639–659PubMedCrossRefGoogle Scholar
  222. 222.
    Muller N (1988) Is there a region of highly structured water around a nonpolar solute molecule? J Solution Chem 17:661–672CrossRefGoogle Scholar
  223. 223.
    Baldwin AJ, Knowles TPJ, Tartaglia GG, Fitzpatrick AW, Devlin GL, Shammas SL, Waudby CA, Mossuto MF, Meehan S, Gras SL, Christodoulou J, Anthony-Cahill SJ, Barker PD, Vendruscolo M, Dobson CM (2011) Metastability of native proteins and the phenomenon of amyloid formation. J Am Chem Soc 133:14160–14163, PMID: 21650202PubMedCrossRefGoogle Scholar
  224. 224.
    Oosawa F, Kasai M (1962) A theory of linear and helical aggregations of macromolecules. J Mol Biol 4:10–21PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Materials and InterfacesWeizmann Institute of ScienceRehovotIsrael
  2. 2.Department of Biotechnology and BiomedicineTechnical University of Denmark, DTULyngbyDenmark

Personalised recommendations