Biophysical Reviews

, Volume 10, Issue 2, pp 453–462 | Cite as

Membrane-mediated amyloid deposition of human islet amyloid polypeptide

  • Kenji Sasahara


Amyloid deposition of human islet amyloid polypeptide (hIAPP) within the islet of Langerhans is closely associated with type II diabetes mellitus. Accumulating evidence indicates that the membrane-mediated aggregation and subsequent deposition of hIAPP are linked to the dysfunction and death of insulin-producing pancreatic β-cells, but the molecular process of hIAPP deposition is poorly understood. In this review, I focus on recent in vitro studies utilizing model membranes to observe the membrane-mediated aggregation/deposition of hIAPP. Membrane surfaces can serve as templates for both hIAPP adsorption and aggregation. Using high-sensitivity surface analyzing/imaging techniques that can characterize the processes of hIAPP aggregation and deposition at the membrane surface, these studies provide valuable insights into the mechanism of membrane damage caused by amyloid deposition of the peptide.


Islet amyloid polypeptide Amyloid deposition Model membranes Membrane disruption Type II diabetes mellitus 


Compliance with ethical standards

Conflict of interest

Kenji Sasahara declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by the author.


  1. Abedini A, Schmidt AM (2013) Mechanisms of islet amyloidosis toxicity in type 2 diabetes. FEBS Lett 587:1119–1127PubMedPubMedCentralCrossRefGoogle Scholar
  2. Anguiano M, Nowak RJ, Lansbury PT Jr (2002) Protofibrillar islet amyloid polypeptide permeabilizes synthetic vesicles by a pore-like mechanism that may be relevant to type II diabetes. Biochemistry 41:11338–11343PubMedCrossRefGoogle Scholar
  3. Apostolidou M, Jayasinghe SA, Langen R (2008) Structure of α-helical membrane-bound human islet amyloid polypeptide and its implications for membrane-mediated misfolding. J Biol Chem 283:17205–17210PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bedrood S, Li Y, Isas JM, Hegde BG, Baxa U, Haworth IS, Langen R (2012) Fibril structure of human islet amyloid polypeptide. J Biol Chem 287:5235–5241PubMedCrossRefGoogle Scholar
  5. Brender JR, Dürr UH, Heyl D, Budarapu MB, Ramamoorthy A (2007) Membrane fragmentation by an amyloidogenic fragment of human islet amyloid polypeptide detected by solid-state NMR spectroscopy of membrane nanotubes. Biochim Biophys Acta 1768:2026–2029PubMedPubMedCentralCrossRefGoogle Scholar
  6. Brender JR, Hartman K, Reid KR, Kennedy RT, Ramamoorthy A (2008) A single mutation in the nonamyloidogenic region of islet amyloid polypeptide greatly reduces toxicity. Biochemistry 47:12680–12688PubMedPubMedCentralCrossRefGoogle Scholar
  7. Brender JR, Hartman K, Nanga RP, Popovych N, de la Salud Bea R, Vivekanandan S, Marsh EN, Ramamoorthy A (2010) Role of zinc in human islet amyloid polypeptide aggregation. J Am Chem Soc 132:8973–8983PubMedPubMedCentralCrossRefGoogle Scholar
  8. Brender JR, Salamekh S, Ramamoorthy A (2012) Membrane disruption and early events in the aggregation of the diabetes related peptide IAPP from a molecular perspective. Acc Chem Res 45:454–462PubMedCrossRefGoogle Scholar
  9. Brender JR, Krishnamoorthy J, Messina GM, Deb A, Vivekanandan S, La Rosa C, Penner-Hahn JE, Ramamoorthy A (2013) Zinc stabilization of prefibrillar oligomers of human islet amyloid polypeptide. Chem Commun 49:3339–3341CrossRefGoogle Scholar
  10. Byström R, Aisenbrey C, Borowik T, Bokvist M, Lindström F, Sani MA, Olofsson A, Gröbner G (2008) Disordered proteins: biological membranes as two-dimensional aggregation matrices. Cell Biochem Biophys 52:175–189PubMedCrossRefGoogle Scholar
  11. Caillon L, Hoffmann AR, Botz A, Khemtemourian L (2016) Molecular structure, membrane interactions, and toxicity of the islet amyloid polypeptide in type 2 diabetes mellitus. J Diabetes Res 2016:5639875PubMedCrossRefGoogle Scholar
  12. Cao P, Marek P, Noor H, Patsalo V, Tu LH, Wang H, Abedini A, Raleigh DP (2013) Islet amyloid: from fundamental biophysics to mechanisms of cytotoxicity. FEBS Lett 587:1106–1118PubMedPubMedCentralCrossRefGoogle Scholar
  13. Cecchi C, Stefani M (2013) The amyloid-cell membrane system. The interplay between the biophysical features of oligomers/fibrils and cell membrane defines amyloid toxicity. Biophys Chem 182:30–43PubMedCrossRefGoogle Scholar
  14. Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366PubMedCrossRefGoogle Scholar
  15. Chiti F, Dobson CM (2017) Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade. Annu Rev Biochem 86:27–68PubMedCrossRefGoogle Scholar
  16. Cho WJ, Trikha S, Jeremic AM (2009) Cholesterol regulates assembly of human islet amyloid polypeptide on model membranes. J Mol Biol 393:765–775PubMedCrossRefGoogle Scholar
  17. Clark A, Nilsson MR (2004) Islet amyloid: a complication of islet dysfunction or an aetiological factor in type 2 diabetes? Diabetologia 47:157–169PubMedCrossRefGoogle Scholar
  18. Clark A, Lewis CE, Willis AC, Cooper GJ, Morris JF, Reid KB, Turner RC (1987) Islet amyloid formed from diabetes-associated peptide may be pathogenic in type-2 diabetes. Lancet 330:231–234CrossRefGoogle Scholar
  19. Cui W, Ma JW, Lei P, Wu WH, Yu YP, Xiang Y, Tong AJ, Zhao YF, Li YM (2009) Insulin is a kinetic but not a thermodynamic inhibitor of amylin aggregation. FEBS J 276:3365–3371PubMedCrossRefGoogle Scholar
  20. DeToma AS, Salamekh S, Ramamoorthy A, Lim MH (2012) Misfolded proteins in Alzheimer’s disease and type II diabetes. Chem Soc Rev 41:608–621PubMedCrossRefGoogle Scholar
  21. Deverall MA, Gindl E, Sinner EK, Besir H, Ruehe J, Saxton MJ, Naumann CA (2005) Membrane lateral mobility obstructed by polymer-tethered lipids studied at the single molecule level. Biophys J 88:1875–1886PubMedCrossRefGoogle Scholar
  22. Dixon MC (2008) Quartz crystal microbalance with dissipation monitoring: enabling real-time characterization of biological materials and their interactions. J Biomol Tech 19:151–158PubMedPubMedCentralGoogle Scholar
  23. Domanov YA, Kinnunen PK (2008) Islet amyloid polypeptide forms rigid lipid–protein amyloid fibrils on supported phospholipid bilayers. J Mol Biol 376:42–54PubMedCrossRefGoogle Scholar
  24. Edidin M (2003) The state of lipid rafts: from model membranes to cells. Ann Rev Biophys Biomol Struct 32:257–283CrossRefGoogle Scholar
  25. Eisenberg D, Jucker M (2012) The amyloid state of proteins in human diseases. Cell 148:1188–1203PubMedPubMedCentralCrossRefGoogle Scholar
  26. Engel MF (2009) Membrane permeabilization by islet amyloid polypeptide. Chem Phys Lipids 160:1–10PubMedCrossRefGoogle Scholar
  27. Engel MF, Yigittop H, Elgersma RC, Rijkers DT, Liskamp RM, de Kruijff B, Höppener JW, Antoinette Killian J (2006) Islet amyloid polypeptide inserts into phospholipid monolayers as monomer. J Mol Biol 356:783–789PubMedCrossRefGoogle Scholar
  28. Engel MF, Khemtémourian L, Kleijer CC, Meeldijk HJ, Jacobs J, Verkleij AJ, de Kruijff B, Killian JA, Höppener JW (2008) Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane. Proc Natl Acad Sci U S A 105:6033–6038PubMedPubMedCentralCrossRefGoogle Scholar
  29. Engel MF, van den Akker CC, Schleeger M, Velikov KP, Koenderink GH, Bonn M (2012) The polyphenol EGCG inhibits amyloid formation less efficiently at phospholipid interfaces than in bulk solution. J Am Chem Soc 134:14781–14788PubMedCrossRefGoogle Scholar
  30. Engelman DM (2005) Membranes are more mosaic than fluid. Nature 438:578–580PubMedCrossRefGoogle Scholar
  31. Foster MC, Leapman RD, Li MX, Atwater I (1993) Elemental composition of secretory granules in pancreatic islets of Langerhans. Biophys J 64:525–532PubMedPubMedCentralCrossRefGoogle Scholar
  32. Gao M, Winter R (2015) The effects of lipid membranes, crowding and osmolytes on the aggregation, and fibrillation propensity of human IAPP. J Diabetes Res 2015:849017PubMedPubMedCentralGoogle Scholar
  33. Gedulin B, Cooper GJ, Young AA (1991) Amylin secretion from the perfused pancreas: dissociation from insulin and abnormal elevation in insulin-resistant diabetic rats. Biochem Biophys Res Comm 180:782–789PubMedCrossRefGoogle Scholar
  34. Gellermann GP, Appel TR, Tannert A, Radestock A, Hortschansky P, Schroeckh V, Leisner C, Lütkepohl T, Shtrasburg S, Röcken C, Pras M, Linke RP, Diekmann S, Fändrich M (2005) Raft lipids as common components of human extracellular amyloid fibrils. Proc Natl Acad Sci U S A 102:6297–6302PubMedPubMedCentralCrossRefGoogle Scholar
  35. Gilead S, Wolfenson H, Gazit E (2006) Molecular mapping of the recognition interface between the islet amyloid polypeptide and insulin. Angew Chem Int Ed Engl 45:6476–6480PubMedCrossRefGoogle Scholar
  36. Glazier R, Salaita K (2017) Supported lipid bilayer platforms to probe cell mechanobiology. Biochim Biophys Acta 1859:1465–1482PubMedCrossRefGoogle Scholar
  37. Goldsbury CS, Cooper GJ, Goldie KN, Müller SA, Saafi EL, Gruijters WT, Misur MP, Engel A, Aebi U, Kistler J (1997) Polymorphic fibrillar assembly of human amylin. J Struct Biol 119:17–27PubMedCrossRefGoogle Scholar
  38. Goldsbury C, Goldie K, Pellaud J, Seelig J, Frey P, Müller SA, Kistler J, Cooper GJ, Aebi U (2000) Amyloid fibril formation from full-length and fragments of amylin. J Struct Biol 130:352–362PubMedCrossRefGoogle Scholar
  39. Gorbenko GP, Kinnunen PK (2006) The role of lipid–protein interactions in amyloid-type protein fibril formation. Chem Phys Lipids 141:72–82PubMedCrossRefGoogle Scholar
  40. Green JD, Kreplak L, Goldsbury C, Li Blatter X, Stolz M, Cooper GS, Seelig A, Kistler J, Aebi U (2004) Atomic force microscopy reveals defects within mica supported lipid bilayers induced by the amyloidogenic human amylin peptide. J Mol Biol 342:877–887PubMedCrossRefGoogle Scholar
  41. Greenwald J, Riek R (2010) Biology of amyloid: structure, function, and regulation. Structure 18:1244–1260PubMedCrossRefGoogle Scholar
  42. Haataja L, Gurlo T, Huang CJ, Butler PC (2008) Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis. Endocr Rev 29:303–316PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hebda JA, Saraogi I, Magzoub M, Hamilton AD, Miranker AD (2009) A peptidomimetic approach to targeting pre-amyloidogenic states in type II diabetes. Chem Biol 16:943–950PubMedPubMedCentralCrossRefGoogle Scholar
  44. Hoppe T, Minton AP (2015) An equilibrium model for the combined effect of macromolecular crowding and surface adsorption on the formation of linear protein fibrils. Biophys J 108:957–966PubMedPubMedCentralCrossRefGoogle Scholar
  45. Höppener JW, Lips CJ (2006) Role of islet amyloid in type 2 diabetes mellitus. Int J Biochem Cell Biol 38:726–736PubMedCrossRefGoogle Scholar
  46. Hull RL, Westermark GT, Westermark P, Kahn SE (2004) Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. J Clin Endocrinol Metab 89:3629–3643PubMedCrossRefGoogle Scholar
  47. Jaikaran ET, Clark A (2001) Islet amyloid and type 2 diabetes: from molecular misfolding to islet pathophysiology. Biochim Biophys Acta 1537:179–203PubMedCrossRefGoogle Scholar
  48. Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC (1999) The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes 48:491–498PubMedCrossRefGoogle Scholar
  49. Jayasinghe SA, Langen R (2005) Lipid membranes modulate the structure of islet amyloid polypeptide. Biochemistry 44:12113–12119PubMedCrossRefGoogle Scholar
  50. Jayasinghe SA, Langen R (2007) Membrane interaction of islet amyloid polypeptide. Biochim Biophys Acta 1768:2002–2009PubMedCrossRefGoogle Scholar
  51. Jurgens CA, Toukatly MN, Fligner CL, Udayasankar J, Subramanian SL, Zraika S, Aston-Mourney K, Carr DB, Westermark P, Westermark GT, Kahn SE, Hull RL (2011) β-cell loss and β-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition. Am J Pathol 178:2632–2640PubMedPubMedCentralCrossRefGoogle Scholar
  52. Kahn SE, D’Alessio DA, Schwartz MW, Fujimoto WY, Ensinck JW, Taborsky GJ Jr, Porte D Jr (1990) Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells. Diabetes 39:634–638PubMedCrossRefGoogle Scholar
  53. Kahn SE, Andrikopoulos S, Verchere CB (1999) Islet amyloid: a long-recognized but underappreciated pathological feature of type 2 diabetes. Diabetes 48:241–253PubMedCrossRefGoogle Scholar
  54. Kajava AV, Aebi U, Steven AC (2005) The parallel superpleated beta-structure as a model for amyloid fibrils of human amylin. J Mol Biol 348:247–252PubMedCrossRefGoogle Scholar
  55. Kapurniotu A (2001) Amyloidogenicity and cytotoxicity of islet amyloid polypeptide. Biopolymers 60:438–459PubMedCrossRefGoogle Scholar
  56. Kayed R, Bernhagen J, Greenfield N, Sweimeh K, Brunner H, Voelter W, Kapurniotu A (1999) Conformational transitions of islet amyloid polypeptide (IAPP) in amyloid formation in vitro. J Mol Biol 287:781–796PubMedCrossRefGoogle Scholar
  57. Khemtémourian L, Killian JA, Höppener JW, Engel MF (2008) Recent insights in islet amyloid polypeptide-induced membrane disruption and its role in β-cell death in type 2 diabetes mellitus. Exp Diabetes Res 2008:421287PubMedPubMedCentralCrossRefGoogle Scholar
  58. Knight JD, Miranker AD (2004) Phospholipid catalysis of diabetic amyloid assembly. J Mol Biol 341:1175–1187PubMedCrossRefGoogle Scholar
  59. Knight JD, Hebda JA, Miranker AD (2006) Conserved and cooperative assembly of membrane-bound α-helical states of islet amyloid polypeptide. Biochemistry 45:9496–9508PubMedCrossRefGoogle Scholar
  60. Knight JD, Williamson JA, Miranker AD (2008) Interaction of membrane-bound islet amyloid polypeptide with soluble and crystalline insulin. Protein Sci 17:1850–1856PubMedPubMedCentralCrossRefGoogle Scholar
  61. Kusumi A, Suzuki KG, Kasai RS, Ritchie K, Fujiwara TK (2011) Hierarchical mesoscale domain organization of the plasma membrane. Trends Biochem Sci 36:604–615PubMedCrossRefGoogle Scholar
  62. Larson JL, Miranker AD (2004) The mechanism of insulin action on islet amyloid polypeptide fiber formation. J Mol Biol 335:221–231PubMedCrossRefGoogle Scholar
  63. Lingwood D, Simons K (2010) Lipid rafts as a membrane-organizing principle. Science 327:46–50PubMedCrossRefGoogle Scholar
  64. Lopes DH, Meister A, Gohlke A, Hauser A, Blume AL, Winter R (2007) Mechanism of islet amyloid polypeptide fibrillation at lipid interfaces studied by infrared reflection absorption spectroscopy. Biophys J 93:3132–3141PubMedPubMedCentralCrossRefGoogle Scholar
  65. Lorenzo A, Razzaboni B, Weir GC, Yankner BA (1994) Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature 368:756–760PubMedCrossRefGoogle Scholar
  66. Luca S, Yau WM, Leapman R, Tycko R (2007) Peptide conformation and supramolecular organization in amylin fibrils: constraints from solid-state NMR. Biochemistry 46:13505–13522PubMedPubMedCentralCrossRefGoogle Scholar
  67. Lutz TA (2012) Control of energy homeostasis by amylin. Cell Mol Life Sci 69:1947–1965PubMedCrossRefGoogle Scholar
  68. Marguet D, Lenne PF, Rigneault H, He HT (2006) Dynamics in the plasma membrane: how to combine fluidity and order. EMBO J 25:3446–3457PubMedPubMedCentralCrossRefGoogle Scholar
  69. Matveyenko AV, Butler PC (2006) β-cell deficit due to increased apoptosis in the human islet amyloid polypeptide transgenic (hip) rat recapitulates the metabolic defects present in type 2 diabetes. Diabetes 55:2106–2114PubMedCrossRefGoogle Scholar
  70. Merzlyakov M, Li E, Hristova K (2006) Directed assembly of surface-supported bilayers with transmembrane helices. Langmuir 22:1247–1253PubMedCrossRefGoogle Scholar
  71. Mirzabekov TA, Lin MC, Kagan BL (1996) Pore formation by the cytotoxic islet amyloid peptide amylin. J Biol Chem 271:1988–1992PubMedCrossRefGoogle Scholar
  72. Nanga RP, Brender JR, Xu J, Veglia G, Ramamoorthy A (2008) Structures of rat and human islet amyloid polypeptide IAPP1–19 in micelles by NMR spectroscopy. Biochemistry 47:12689–12697PubMedPubMedCentralCrossRefGoogle Scholar
  73. Nanga RP, Brender JR, Xu J, Hartman K, Subramanian V, Ramamoorthy A (2009) Three-dimensional structure and orientation of rat islet amyloid polypeptide protein in a membrane environment by solution NMR spectroscopy. J Am Chem Soc 131:8252–8261PubMedPubMedCentralCrossRefGoogle Scholar
  74. Nanga RP, Brender JR, Vivekanandan S, Ramamoorthy A (2011) Structure and membrane orientation of IAPP in its natively amidated form at physiological pH in a membrane environment. Biochim Biophys Acta 1808:2337–2342PubMedPubMedCentralCrossRefGoogle Scholar
  75. Nguyen PT, Andraka N, De Carufel CA, Bourgault S (2015) Mechanistic contributions of biological cofactors in islet amyloid polypeptide amyloidogenesis. J Diabetes Res 2015:515307PubMedPubMedCentralCrossRefGoogle Scholar
  76. Okazaki T, Inaba T, Tatsu Y, Tero R, Urisu T, Morigaki K (2009) Polymerized lipid bilayers on a solid substrate: morphologies and obstruction of lateral diffusion. Langmuir 25:345–351PubMedCrossRefGoogle Scholar
  77. Owen DM, Williamson D, Rentero C, Gaus K (2009) Quantitative microscopy: protein dynamics and membrane organisation. Traffic 10:962–971PubMedCrossRefGoogle Scholar
  78. Padrick SB, Miranker AD (2001) Islet amyloid polypeptide: identification of long-range contacts and local order on the fibrillogenesis pathway. J Mol Biol 308:783–794PubMedCrossRefGoogle Scholar
  79. Patel HR, Pithadia AS, Brender JR, Fierke CA, Ramamoorthy A (2014) In search of aggregation pathways of IAPP and other amyloidogenic proteins: finding answers through NMR spectroscopy. J Phys Chem Lett 5:1864–1870PubMedCrossRefGoogle Scholar
  80. Pithadia A, Brender JR, Fierke CA, Ramamoorthy A (2016) Inhibition of IAPP aggregation and toxicity by natural products and derivatives. J Diabetes Res 2016:2046327PubMedCrossRefGoogle Scholar
  81. Porat Y, Kolusheva S, Jelinek R, Gazit E (2003) The human islet amyloid polypeptide forms transient membrane-active prefibrillar assemblies. Biochemistry 42:10971–10977PubMedCrossRefGoogle Scholar
  82. Quist A, Doudevski I, Lin H, Azimova R, Ng D, Frangione B, Kagan B, Ghiso J, Lal R (2005) Amyloid ion channels: a common structural link for protein-misfolding disease. Proc Natl Acad Sci U S A 102:10427–10432PubMedPubMedCentralCrossRefGoogle Scholar
  83. Radovan D, Opitz N, Winter R (2009) Fluorescence microscopy studies on islet amyloid polypeptide fibrillation at heterogeneous and cellular membrane interfaces and its inhibition by resveratrol. FEBS Lett 583:1439–1445PubMedCrossRefGoogle Scholar
  84. Relini A, Cavalleri O, Rolandi R, Gliozzi A (2009) The two-fold aspect of the interplay of amyloidogenic proteins with lipid membranes. Chem Phys Lipids 158:1–9PubMedCrossRefGoogle Scholar
  85. Relini A, Marano N, Gliozzi A (2014) Probing the interplay between amyloidogenic proteins and membranes using lipid monolayers and bilayers. Adv Colloid Interf Sci 207:81–92CrossRefGoogle Scholar
  86. Richter RP, Bérat R, Brisson AR (2006) Formation of solid-supported lipid bilayers: an integrated view. Langmuir 22:3497–3505PubMedCrossRefGoogle Scholar
  87. Ritzel RA, Meier JJ, Lin CY, Veldhuis JD, Butler PC (2007) Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets. Diabetes 56:65–71PubMedCrossRefGoogle Scholar
  88. Rustenbeck I, Matthies A, Lenzen S (1994) Lipid composition of glucose-stimulated pancreatic islets and insulin-secreting tumor cells. Lipids 29:685–692PubMedCrossRefGoogle Scholar
  89. Salamekh S, Brender JR, Hyung SJ, Nanga RP, Vivekanandan S, Ruotolo BT, Ramamoorthy A (2011) A two-site mechanism for the inhibition of IAPP amyloidogenesis by zinc. J Mol Biol 410:294–306PubMedPubMedCentralCrossRefGoogle Scholar
  90. Sasahara K, Hall D, Hamada D (2010) Effect of lipid type on the binding of lipid vesicles to islet amyloid polypeptide amyloid fibrils. Biochemistry 49:3040–3048PubMedCrossRefGoogle Scholar
  91. Sasahara K, Morigaki K, Okazaki T, Hamada D (2012) Binding of islet amyloid polypeptide to supported lipid bilayers and amyloid aggregation at the membranes. Biochemistry 51:6908–6919PubMedCrossRefGoogle Scholar
  92. Sasahara K, Morigaki K, Shinya K (2014) Amyloid aggregation and deposition of human islet amyloid polypeptide at membrane interfaces. FEBS J 281:2597–2612PubMedCrossRefGoogle Scholar
  93. Sciacca MF, Kotler SA, Brender JR, Chen J, Lee DK, Ramamoorthy A (2012a) Two-step mechanism of membrane disruption by Aβ through membrane fragmentation and pore formation. Biophys J 103:702–710PubMedPubMedCentralCrossRefGoogle Scholar
  94. Sciacca MF, Brender JR, Lee DK, Ramamoorthy A (2012b) Phosphatidylethanolamine enhances amyloid fiber-dependent membrane fragmentation. Biochemistry 51:7676–7684PubMedPubMedCentralCrossRefGoogle Scholar
  95. Sciacca MF, Lolicato F, Di Mauro G, Milardi D, D’Urso L, Satriano C, Ramamoorthy A, La Rosa C (2016) The role of cholesterol in driving IAPP-membrane interactions. Biophys J 111:140–151PubMedPubMedCentralCrossRefGoogle Scholar
  96. Seeliger J, Weise K, Opitz N, Winter R (2012) The effect of Aβ on IAPP aggregation in the presence of an isolated β-cell membrane. J Mol Biol 421:348–363PubMedPubMedCentralCrossRefGoogle Scholar
  97. Sellin D, Yan LM, Kapurniotu A, Winter R (2010) Suppression of IAPP fibrillation at anionic lipid membranes via IAPP-derived amyloid inhibitors and insulin. Biophys Chem 150:73–79PubMedCrossRefGoogle Scholar
  98. Stefani M, Rigacci S (2013) Protein folding and aggregation into amyloid: the interference by natural phenolic compounds. Int J Mol Sci 14:12411–12457PubMedPubMedCentralCrossRefGoogle Scholar
  99. Sumner Makin O, Serpell LC (2004) Structural characterisation of islet amyloid polypeptide fibrils. J Mol Biol 335:1279–1288PubMedCrossRefGoogle Scholar
  100. Sunde M, Blake C (1997) The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv Protein Chem 50:123–159PubMedCrossRefGoogle Scholar
  101. Susa AC, Wu C, Bernstein SL, Dupuis NF, Wang H, Raleigh DP, Shea JE, Bowers MT (2014) Defining the molecular basis of amyloid inhibitors: human islet amyloid polypeptide–insulin interactions. J Am Chem Soc 136:12912–12919PubMedPubMedCentralCrossRefGoogle Scholar
  102. Tomasello MF, Sinopoli A, Pappalardo G (2015) On the environmental factors affecting the structural and cytotoxic properties of IAPP peptides. J Diabetes Res 2015:918573PubMedPubMedCentralCrossRefGoogle Scholar
  103. Trikha S, Jeremic AM (2011) Clustering and internalization of toxic amylin oligomers in pancreatic cells require plasma membrane cholesterol. J Biol Chem 286:36086–36097PubMedPubMedCentralCrossRefGoogle Scholar
  104. Vestergaard MD, Hamada T, Takagi M (2008) Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity. Biotechnol Bioeng 99:753–763PubMedCrossRefGoogle Scholar
  105. Wei L, Jiang P, Yau YH, Summer H, Shochat SG, Mu Y, Pervushin K (2009) Residual structure in islet amyloid polypeptide mediates its interactions with soluble insulin. Biochemistry 48:2368–2376PubMedCrossRefGoogle Scholar
  106. Weise K, Radovan D, Gohlke A, Opitz N, Winter R (2010) Interaction of hIAPP with model raft membranes and pancreatic beta-cells: cytotoxicity of hIAPP oligomers. ChemBioChem 11:1280–1290PubMedCrossRefGoogle Scholar
  107. Westermark P (1973) Fine structure of islets of Langerhans in insular amyloidosis. Virchows Arch A Pathol Pathol Anat 359:1–18PubMedCrossRefGoogle Scholar
  108. Westermark P, Engström U, Johnson KH, Westermark GT, Betsholtz C (1990) Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation. Proc Natl Acad Sci U S A 87:5036–5040PubMedPubMedCentralCrossRefGoogle Scholar
  109. Westermark P, Andersson A, Westermark GT (2011) Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev 91:795–826PubMedCrossRefGoogle Scholar
  110. Williamson JA, Loria JP, Miranker AD (2009) Helix stabilization precedes aqueous and bilayer-catalyzed fiber formation in islet amyloid polypeptide. J Mol Biol 393:383–396PubMedPubMedCentralCrossRefGoogle Scholar
  111. Wiltzius JJ, Sievers SA, Sawaya MR, Cascio D, Popov D, Riekel C, Eisenberg D (2008) Atomic structure of the cross-β spine of islet amyloid polypeptide (amylin). Protein Sci 17:1467–1474PubMedPubMedCentralCrossRefGoogle Scholar
  112. Yamazaki V, Sirenko O, Schafer RJ, Groves JT (2005) Lipid mobility and molecular binding in fluid lipid membranes. J Am Chem Soc 127:2826–2827PubMedCrossRefGoogle Scholar
  113. Yanagi K, Ashizaki M, Yagi H, Sakurai K, Lee YH, Goto Y (2011) Hexafluoroisopropanol induces amyloid fibrils of islet amyloid polypeptide by enhancing both hydrophobic and electrostatic interactions. J Biol Chem 286:23959–23966PubMedPubMedCentralCrossRefGoogle Scholar
  114. Zhang X, St. Clair JR, London E, Raleigh DP (2017) Islet amyloid polypeptide membrane interactions: effects of membrane composition. Biochemistry 56:376–390PubMedPubMedCentralCrossRefGoogle Scholar

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© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Institute for Protein ResearchOsaka UniversitySuitaJapan

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