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Milardi, D. Membrane-Bound Amyloids. Encyclopedia. Available online: https://encyclopedia.pub/entry/9188 (accessed on 21 December 2025).
Milardi D. Membrane-Bound Amyloids. Encyclopedia. Available at: https://encyclopedia.pub/entry/9188. Accessed December 21, 2025.
Milardi, Danilo. "Membrane-Bound Amyloids" Encyclopedia, https://encyclopedia.pub/entry/9188 (accessed December 21, 2025).
Milardi, D. (2021, April 29). Membrane-Bound Amyloids. In Encyclopedia. https://encyclopedia.pub/entry/9188
Milardi, Danilo. "Membrane-Bound Amyloids." Encyclopedia. Web. 29 April, 2021.
Membrane-Bound Amyloids
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This entry is adapted from the peer-reviewed paper 10.3390/biophysica1020011

Many reports suggest that the toxic properties of amyloid aggregates are correlated with their ability to damage cell membranes. However, the molecular mechanisms causing toxic amyloid/membrane interactions are still far to be completely elucidated. This review aims at describing the mutual relationships linking abnormal protein conformational transition and self-assembly into amyloid aggregates with membrane damage.

amylin lipid bilayer protein aggregation misfolding amyloid peptide prion

1. Aβ/Membrane Complexes

Lipids are essential components of neuron membranes. Since APP processing by α-, β-, and γ-secretases occurs within the lipid bilayer, membrane components are believed to participate in the regulation of Aβ levels. In addition, accumulating evidence suggests abnormal lipid levels in the AD brain, indicating that aberrant interactions of Aβ amyloid with the membrane may play a significant role in AD pathogenesis [1][2]. Aβ may interact with membranes in different ways and modify their biophysical properties [3]. Aβ peptide may insert into the lipid hydrocarbon core generating a pore-like channel or may be placed (and aggregate) over the membrane surface [2]. Independently of the type of interaction, membrane-bound Aβ may damage neurons, worsen synaptic signaling, and eventually lead to apoptosis [2]. Interestingly, just as the membrane can affect Aβ fibril growth, peptide insertion may alter the physic-chemical properties of the membrane. Aβ peptide/membrane interactions are driven by both electrostatic and hydrophobic forces which cooperatively catalyze amyloid growth on the membrane surface. Zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid increases the Aβ fibril formation kinetics if compared to water [4]. Likewise, negatively charged phospholipids, such as 1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG), speed up amyloid growth [5].
Amyloid growth on the membrane surface can affect the structure of the lipid bilayer [6]. As an example, Aβ insertion into the hydrocarbon core of 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (POPE)-rich membranes causes remarkable changes into bilayer curvature [7]. Cholesterol is known to enhance the rate of fibril formation in membranes by accelerating Aβ nucleation [8]. Gangliosides catalyze Aβ oligomerization in neuronal membranes: in fact, Aβ binds ganglioside GM1 in lipid-raft membrane [9]. Of note, Aβ fibrils formed in GM1-enriched membranes were found to be more toxic than the fibrils growth in aqueous solution [10]. Cell-free experiments carried out using neuron-mimicking total lipid brain extract (TLBE) vesicles have shown that Aβ fibril growth is not significantly faster in pure water [11][12]. An accepted hypothesis indicates that alterations in lipid bilayer owing to Aβ interactions may induce toxicity through molecular mechanisms mainly steered by electrostatic forces, in analogy to the well-known action of antimicrobial peptides [1]. Small-sized, soluble Aβ amyloid aggregates with neurotoxic activity were first described by Lambert et al. and were named “Aβ-Derived Diffusible Ligands” (ADDLs) [13]. Aβ oligomers are highly heterogeneous in size, morphology, and toxicity. Currently, many membrane active Aβ oligomers have been reported such as dimeric [14][15][16][17][18][19][20], trimeric [14][15][19][21], tetrameric [15][18][19], pentameric [17][19], hexameric [18][19][21][22], decameric [18], dodecameric [21][22] and 24-meric assemblies [23][24][25]. Small-sized Aβ assemblies are normally short-lived and with a globular morphology. Their β-sheet content increases with their size, leading eventually to the formation of protofibrils. However, the relationship linking Aβ oligomers toxicity with their morphology is still a highly debated issue: it seems that toxicity increases with the oligomers size reaching a maximum for to dodecameric assemblies. Membrane-embedded Aβ oligomers characterized by a β-sheet annular structure have been reported to form pores in lipid bilayer and to trigger cytotoxic processes [26][27].

2. IAPP–Membrane Interactions

Biophysical experiments addressing IAPP amyloid growth and pore formation in model membranes with different lipid composition including DOPC, POPC, sphingomyelin, negatively charged phospholipids (POPS) and cholesterol, have demonstrated that zwitterionic phospholipids have a poor impact on amyloid growth but promote pore formation [28][29][30][31][32]. Cholesterol, when present in lipid membranes reduces IAPP pores and fibrils formation [33]. Concerning the role played by lipid vesicles in managing IAPP intra- and extra-cellular trafficking, some authors have investigated the interaction between IAPP, and exosomes obtained from T2DM patients and healthy people as a control. Exosomes from healthy subjects inhibited the formation of IAPP fibril growth. By contrast, exosomes extracted from diabetic individuals had no effect on fibril formation. Lipid composition of exosomes is believed to steer interactions with IAPP. In fact, differently from neuronal exosomes, no anionic lipids were found in exosomes from pancreatic tissues [34]. It is widely accepted that anionic phospholipids catalyze fibrillogenesis. However, additional experimental data are needed to propose more accurate models depicting the role of exosomes in IAPP amyloidogenesis and diabetes development. Molecular simulations of membrane-bound hIAPP from different species have been carried out [35][36][37] including the non-toxic, non-amyloidogenic rIAPP [38]. Molecular dynamics (MD) simulations revealed short-lived α-helical and β-sheet structures throughout IAPP adsorption onto an anionic POPG (palmitoyl oleoyl phosphatidylglycerol) surface of a lipid bilayer [36]. Membrane adsorbed IAPP monomers produced bending of the bilayer. HIAPP interaction with zwitterionic POPC (phosphatidylcholine) bilayer was investigated by MD simulations, and kinetics measurements of dye release from LUVs [39]. Both simulations and experiments demonstrated that IAPP insertion into zwitterionic membranes is assisted by non-vesicular lipids that are present in solution at their critical micellar concentration (cmc). Other authors have adopted coupled coarse-grained/umbrella sampling molecular dynamics simulations to investigate the interactions of hIAPP with ganglioside-rich membranes [35]. These simulations indicate that hIAPP locate in ganglioside-rich membrane regions due to electrostatic interactions promoting adhesion of cationic hIAPP peptides with anionic gangliosides. The three positively charged amino acids K1, R11 and H18 located in the N-terminal domain of IAPP are known to play a major role in driving interactions with negatively charged membranes [40].

3. Prion–Membrane Interactions

Many reports suggest that small soluble and transient oligomeric aggregates, due to their high propensity to associate with membranes, are the most active agent in driving amyloid toxicity. From these observations on IAPP, Aβ and other amyloids stemmed the “toxic oligomers hypothesis”. This hypothesis was also extended to prion proteins [41][42][43]. Electrophysiology experiments have shown an increased conductance in membranes containing zwitterionic 1,2-diphytanoyl-sn-glycero-3-phosphocholine interacting with PrP(90–231) by pore formation [44]. Measurements on negatively charged phospholipid interaction with human prion amyloidogenic fragment PrP(185–206) described the formation of channel but not of fibrils [45]. Studies on the PrP(180–193) fragment suggest hydrophobicity as the major driving force in protein interaction with membranes [46][47]. Additionally, PrP(106–126) and huPrP60-91 showed a noticeable tendency to penetrate the lipid bilayer with an associated conformational transition toward a β-sheet structure affected by the presence of metal ions. Copper ions favor fragment insertion, whereas zinc ions inhibit fragment transfer from the aqueous phase to the bilayer [48][49]. This finding suggests that, in the transfer PrP from the aqueous phase to the bilayer core, the electrostatic force cannot be overlooked. Additionally, some reports show that binding of PrP to artificial membrane depends on the type of lipid [50] and follows the decreasing order of affinity POPG > DPPC > rafts [51].

References

  1. Drolle, E.; Negoda, A.; Hammond, K.; Pavlov, E.; Leonenko, Z. Changes in Lipid Membranes May Trigger Amyloid Toxicity in Alzheimer’s Disease. PLoS ONE 2017.
  2. Niu, Z.; Zhang, Z.; Zhao, W.; Yang, J. Interactions between Amyloid β Peptide and Lipid Membranes. Biochim. Biophys. Acta Biomembr. 2018, 1860, 1663–1669.
  3. Peters, I.; Igbavboa, U.; Schütt, T.; Haidari, S.; Hartig, U.; Rosello, X.; Böttner, S.; Copanaki, E.; Deller, T.; Kögel, D.; et al. The Interaction of Beta-Amyloid Protein with Cellular Membranes Stimulates Its Own Production. Biochim. Biophys. Acta Biomembr. 2009, 1788, 964–972.
  4. Korshavn, K.J.; Satriano, C.; Lin, Y.; Zhang, R.; Dulchavsky, M.; Bhunia, A.; Ivanova, M.I.; Lee, Y.-H.; La Rosa, C.; Lim, M.H.; et al. Reduced Lipid Bilayer Thickness Regulates the Aggregation and Cytotoxicity of Amyloid-β. J. Biol. Chem. 2017, 292, 4638–4650.
  5. Niu, Z.; Zhao, W.; Zhang, Z.; Xiao, F.; Tang, X.; Yang, J. The Molecular Structure of Alzheimer β-Amyloid Fibrils Formed in the Presence of Phospholipid Vesicles. Angew. Chem. Int. Ed. 2014, 53, 9294–9297.
  6. Cazzaniga, E.; Bulbarelli, A.; Lonati, E.; Orlando, A.; Re, F.; Gregori, M.; Masserini, M. Abeta Peptide Toxicity Is Reduced after Treatments Decreasing Phosphatidylethanolamine Content in Differentiated Neuroblastoma Cells. Neurochem. Res. 2011, 36, 863–869.
  7. Pannuzzo, M.; Milardi, D.; Raudino, A.; Karttunen, M.; La Rosa, C. Analytical Model and Multiscale Simulations of Aβ Peptide Aggregation in Lipid Membranes: Towards a Unifying Description of Conformational Transitions, Oligomerization and Membrane Damage. Phys. Chem. Chem. Phys. 2013, 15, 8940–8951.
  8. Habchi, J.; Chia, S.; Galvagnion, C.; Michaels, T.C.T.; Bellaiche, M.M.J.; Ruggeri, F.S.; Sanguanini, M.; Idini, I.; Kumita, J.R.; Sparr, E.; et al. Cholesterol Catalyses Aβ42 Aggregation through a Heterogeneous Nucleation Pathway in the Presence of Lipid Membranes. Nat. Chem. 2018, 10, 673–683.
  9. Matsuzaki, K. How Do Membranes Initiate Alzheimer’s Disease? Formation of Toxic Amyloid Fibrils by the Amyloid β-Protein on Ganglioside Clusters. Acc. Chem. Res. 2014, 47, 2397–2404.
  10. Okada, T.; Ikeda, K.; Wakabayashi, M.; Ogawa, M.; Matsuzaki, K. Formation of Toxic Abeta(1-40) Fibrils on GM1 Ganglioside-Containing Membranes Mimicking Lipid Rafts: Polymorphisms in Abeta(1-40) Fibrils. J. Mol. Biol. 2008, 382, 1066–1074.
  11. Sani, M.-A.; Gehman, J.D.; Separovic, F. Lipid Matrix Plays a Role in Abeta Fibril Kinetics and Morphology. FEBS Lett. 2011, 585, 749–754.
  12. Sciacca, M.F.M.; Monaco, I.; La Rosa, C.; Milardi, D. The Active Role of Ca2+ Ions in Aβ-Mediated Membrane Damage. Chem. Commun. 2018, 54, 3629–3631.
  13. Lambert, M.P.; Barlow, A.K.; Chromy, B.A.; Edwards, C.; Freed, R.; Liosatos, M.; Morgan, T.E.; Rozovsky, I.; Trommer, B.; Viola, K.L.; et al. Diffusible, Nonfibrillar Ligands Derived from Aβ1–42 Are Potent Central Nervous System Neurotoxins. Proc. Natl. Acad. Sci. USA 1998, 95, 6448–6453.
  14. Shankar, G.M.; Li, S.; Mehta, T.H.; Garcia-Munoz, A.; Shepardson, N.E.; Smith, I.; Brett, F.M.; Farrell, M.A.; Rowan, M.J.; Lemere, C.A.; et al. Amyloid-β Protein Dimers Isolated Directly from Alzheimer’s Brains Impair Synaptic Plasticity and Memory. Nat. Med. 2008, 14, 837–842.
  15. Townsend, M.; Shankar, G.M.; Mehta, T.; Walsh, D.M.; Selkoe, D.J. Effects of Secreted Oligomers of Amyloid Beta-Protein on Hippocampal Synaptic Plasticity: A Potent Role for Trimers. J. Physiol. 2006, 572, 477–492.
  16. Müller-Schiffmann, A.; Herring, A.; Abdel-Hafiz, L.; Chepkova, A.N.; Schäble, S.; Wedel, D.; Horn, A.H.C.; Sticht, H.; de Souza Silva, M.A.; Gottmann, K.; et al. Amyloid-β Dimers in the Absence of Plaque Pathology Impair Learning and Synaptic Plasticity. Brain 2016, 139, 509–525.
  17. Ono, K.; Condron, M.M.; Teplow, D.B. Structure–Neurotoxicity Relationships of Amyloid β-Protein Oligomers. Proc. Natl. Acad. Sci. USA 2009, 106, 14745–14750.
  18. Bernstein, S.L.; Dupuis, N.F.; Lazo, N.D.; Wyttenbach, T.; Condron, M.M.; Bitan, G.; Teplow, D.B.; Shea, J.-E.; Ruotolo, B.T.; Robinson, C.V.; et al. Amyloid-β Protein Oligomerization and the Importance of Tetramers and Dodecamers in the Aetiology of Alzheimer’s Disease. Nat. Chem. 2009, 1, 326–331.
  19. Bitan, G.; Kirkitadze, M.D.; Lomakin, A.; Vollers, S.S.; Benedek, G.B.; Teplow, D.B. Amyloid β-Protein (Aβ) Assembly: Aβ40 and Aβ42 Oligomerize through Distinct Pathways. Proc. Natl. Acad. Sci. USA 2003, 100, 330–335.
  20. O’Nuallain, B.; Freir, D.B.; Nicoll, A.J.; Risse, E.; Ferguson, N.; Herron, C.E.; Collinge, J.; Walsh, D.M. Amyloid Beta-Protein Dimers Rapidly Form Stable Synaptotoxic Protofibrils. J. Neurosci. 2010, 30, 14411–14419.
  21. Lesné, S.; Koh, M.T.; Kotilinek, L.; Kayed, R.; Glabe, C.G.; Yang, A.; Gallagher, M.; Ashe, K.H. A Specific Amyloid-Beta Protein Assembly in the Brain Impairs Memory. Nature 2006, 440, 352–357.
  22. Economou, N.J.; Giammona, M.J.; Do, T.D.; Zheng, X.; Teplow, D.B.; Buratto, S.K.; Bowers, M.T. Amyloid β-Protein Assembly and Alzheimer’s Disease: Dodecamers of Aβ42, but Not of Aβ40, Seed Fibril Formation. J. Am. Chem. Soc. 2016, 138, 1772–1775.
  23. Gong, Y.; Chang, L.; Viola, K.L.; Lacor, P.N.; Lambert, M.P.; Finch, C.E.; Krafft, G.A.; Klein, W.L. Alzheimer’s Disease-Affected Brain: Presence of Oligomeric Aβ Ligands (ADDLs) Suggests a Molecular Basis for Reversible Memory Loss. Proc. Natl. Acad. Sci. USA 2003, 100, 10417–10422.
  24. Kumar, A.; Paslay, L.C.; Lyons, D.; Morgan, S.E.; Correia, J.J.; Rangachari, V. Specific Soluble Oligomers of Amyloid-β Peptide Undergo Replication and Form Non-Fibrillar Aggregates in Interfacial Environments. J. Biol. Chem. 2012, 287, 21253–21264.
  25. Breydo, L.; Uversky, V.N. Structural, Morphological, and Functional Diversity of Amyloid Oligomers. FEBS Lett. 2015, 589, 2640–2648.
  26. Kokubo, H.; Kayed, R.; Glabe, C.G.; Staufenbiel, M.; Saido, T.C.; Iwata, N.; Yamaguchi, H. Amyloid Beta Annular Protofibrils in Cell Processes and Synapses Accumulate with Aging and Alzheimer-Associated Genetic Modification. Int. J. Alzheimers Dis. 2009.
  27. Kayed, R.; Pensalfini, A.; Margol, L.; Sokolov, Y.; Sarsoza, F.; Head, E.; Hall, J.; Glabe, C. Annular Protofibrils Are a Structurally and Functionally Distinct Type of Amyloid Oligomer. J. Biol. Chem. 2009, 284, 4230–4237.
  28. Xu, W.; Wei, G.; Su, H.; Nordenskiöld, L.; Mu, Y. Effects of Cholesterol on Pore Formation in Lipid Bilayers Induced by Human Islet Amyloid Polypeptide Fragments: A Coarse-Grained Molecular Dynamics Study. Phys. Rev. E 2011, 84, 051922.
  29. Caillon, L.; Lequin, O.; Khemtémourian, L. Evaluation of Membrane Models and Their Composition for Islet Amyloid Polypeptide-Membrane Aggregation. Biochim. Biophys. Acta (BBA) Biomembr. 2013, 1828, 2091–2098.
  30. Caillon, L.; Duma, L.; Lequin, O.; Khemtemourian, L. Cholesterol Modulates the Interaction of the Islet Amyloid Polypeptide with Membranes. Mol. Membr. Biol. 2014, 31, 239–249.
  31. Wakabayashi, M.; Matsuzaki, K. Ganglioside-Induced Amyloid Formation by Human Islet Amyloid Polypeptide in Lipid Rafts. FEBS Lett. 2009, 583, 2854–2858.
  32. Lozano, M.M.; Hovis, J.S.; Moss, F.R.; Boxer, S.G. Dynamic Reorganization and Correlation among Lipid Raft Components. J. Am. Chem. Soc. 2016, 138, 9996–10001.
  33. Zhang, X.; St. Clair, J.R.; London, E.; Raleigh, D.P. Islet Amyloid Polypeptide Membrane Interactions: Effects of Membrane Composition. Biochemistry 2017, 56, 376–390.
  34. Ribeiro, D.; Horvath, I.; Heath, N.; Hicks, R.; Forslöw, A.; Wittung-Stafshede, P. Extracellular Vesicles from Human Pancreatic Islets Suppress Human Islet Amyloid Polypeptide Amyloid Formation. Proc. Natl. Acad. Sci. USA 2017.
  35. Christensen, M.H.; Schiott, B. Membrane Interactions of IAPP. Biophys. J. 2019, 116, 491.
  36. Qiao, Q. Formation of Alpha-Helical and Beta-Sheet Structures in Membrane-Bound Human IAPP Monomer and the Resulting Membrane Deformation. Phys. Chem. Chem. Phys. 2019, 21, 20239–20251.
  37. Alves, N.A.; Frigori, R.B. In Silico Comparative Study of Human and Porcine Amylin. J. Phys. Chem. B 2018, 122, 10714–10721.
  38. Su, X. All-Atom Structure Ensembles of Islet Amyloid Polypeptides Determined by Enhanced Sampling and Experiment Data Restraints. Proteins-Struct. Funct. Bioinform. 2019, 87, 541–550.
  39. Scollo, F.; Tempra, C.; Lolicato, F.; Sciacca, M.F.M.; Raudino, A.; Milardi, D.; La Rosa, C. Phospholipids Critical Micellar Concentrations Trigger Different Mechanisms of Intrinsically Disordered Proteins Interaction with Model Membranes. J. Phys. Chem. Lett. 2018, 9, 5125–5129.
  40. Milardi, D.; Gazit, E.; Radford, S.E.; Xu, Y.; Gallardo, R.U.; Caflisch, A.; Westermark, G.T.; Westermark, P.; La Rosa, C.; Ramamoorthy, A. Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes. Chem. Rev. 2021, 121, 1845–1893.
  41. Hu, P.P.; Huang, C.Z. Prion Protein: Structural Features and Related Toxicity. Acta Biochim. Biophys. Sin. 2013, 45, 435–441.
  42. Kagan, B.L. Membrane Pores in the Pathogenesis of Neurodegenerative Disease. In Progress in Molecular Biology and Translational Science; Elsevier: Amsterdam, The Netherlands, 2012; Volume 107, pp. 295–325. ISBN 978-0-12-385883-2.
  43. Ambadi Thody, S.; Mathew, M.K.; Udgaonkar, J.B. Mechanism of Aggregation and Membrane Interactions of Mammalian Prion Protein. Biochim. Biophys. Acta (BBA) Biomembr. 2018, 1860, 1927–1935.
  44. Paulis, D.; Maras, B.; Schininà, M.E.; di Francesco, L.; Principe, S.; Galeno, R.; Abdel-Haq, H.; Cardone, F.; Florio, T.; Pocchiari, M.; et al. The Pathological Prion Protein Forms Ionic Conductance in Lipid Bilayer. Neurochem. Int. 2011, 59, 168–174.
  45. Sonkina, S.; Tukhfatullina, I.I.; Benseny-Cases, N.; Ionov, M.; Bryszewska, M.; Salakhutdinov, B.A.; Cladera, J. Interaction of the Prion Protein Fragment PrP 185-206 with Biological Membranes: Effect on Membrane Permeability. J. Pept. Sci. 2010, 16, 342–348.
  46. Grasso, D.; Milardi, D.; Guantieri, V.; La Rosa, C.; Rizzarelli, E. Interaction of Prion Peptide PrP 180-193 with DPPC Model Membranes: A Thermodynamic Study. New J. Chem. 2003, 27, 359–364.
  47. Pappalardo, M.; Milardi, D.; La Rosa, C.; Zannoni, C.; Rizzarelli, E.; Grasso, D. A Molecular Dynamics Study on the Conformational Stability of PrP 180–193 Helix II Prion Fragment. Chem. Phys. Lett. 2004, 390, 511–516.
  48. Grasso, D.; Milardi, D.; La Rosa, C.; Rizzarelli, E. The Different Role of Cu++ and Zn++ Ions in Affecting the Interaction of Prion Peptide PrP106-126 with Model Membranes. Chem. Commun. 2004, 246–247.
  49. Di Natale, G.; Pappalardo, G.; Milardi, D.; Sciacca, M.F.M.; Attanasio, F.; La Mendola, D.; Rizzarelli, E. Membrane Interactions and Conformational Preferences of Human and Avian Prion N-Terminal Tandem Repeats: The Role of Copper(II) Ions, PH, and Membrane Mimicking Environments. J. Phys. Chem. B 2010, 114, 13830–13838.
  50. Sanghera, N.; Swann, M.J.; Ronan, G.; Pinheiro, T.J.T. Insight into Early Events in the Aggregation of the Prion Protein on Lipid Membranes. Biochim. Biophys. Acta (BBA) Biomembr. 2009, 1788, 2245–2251.
  51. Critchley, P.; Kazlauskaite, J.; Eason, R.; Pinheiro, T.J.T. Binding of Prion Proteins to Lipid Membranes. Biochem. Biophys. Res. Commun. 2004, 313, 559–567.
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