Fibrillar and Nonfibrillar Amyloid Beta Structures Drive Two Modes of Membrane-Mediated Toxicity

Vander Zanden, Crystal M.; Wampler, Lois; Bowers, Isabella; Watkins, Erik B.; Majewski, Jaroslaw; Chi, Eva Y.

doi:10.1021/acs.langmuir.9b02484

Title: Fibrillar and Nonfibrillar Amyloid Beta Structures Drive Two Modes of Membrane-Mediated Toxicity

Journal Article · Wed Sep 11 00:00:00 EDT 2019 · Langmuir

DOI:https://doi.org/10.1021/acs.langmuir.9b02484· OSTI ID:1599452

^[1]; Wampler, Lois ^[2]; Bowers, Isabella ^[3];

^[4]; Majewski, Jaroslaw ^[5];

^[6]

Univ. of New Mexico, Albuquerque, NM (United States); Univ. of Colorado, Colorado Springs, CO (United States)
Department of Biomedical Engineering, Texas A&M University, College Station, Texas 77843, United States
Texas A & M Univ., College Station, TX (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Univ. of New Mexico, Albuquerque, NM (United States); National Science Foundation (NSF), Alexandria, VA (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Univ. of New Mexico, Albuquerque, NM (United States)

In Alzheimer’s disease, the amyloid-beta peptide (Aβ) is implicated in neuronal toxicity via interactions with the cell membrane. Monomeric Aβ (Aβm) is intrinsically disordered, but it can adopt a range of aggregated conformations with varying toxicities from short fibrillar oligomers (FO), to globular nonfibrillar oligomers (NFO), and full-length amyloid fibrils. NFO is considered to be the most toxic, followed by fibrils, and finally Aβm. To elucidate molecular-level membrane interactions that contribute to their different toxicities, we used liquid surface X-ray scattering and Langmuir trough insertion assays to compare Aβm, FO, and NFO surface activities and interactions with anionic DMPG lipid monolayers at the air/water interface. All Aβ species were highly surface active and rapidly adopted β-sheet rich structures upon adsorption to the air/water interface. Likewise, all Aβ species had affinity for the anionic membrane. Aβm rapidly converted to β-sheet rich assemblies upon binding the membrane, and these aggregated structures of Aβm and FO disrupted hexagonally packed lipid domains and resulted in membrane thinning and instability. In contrast, NFO perturbed membrane structure by extracting lipids from the air/water interface and causing macroscale membrane deformations. Altogether, our results support two models for membrane-mediated Aβ toxicity: fibril-induced reorganization of lipid packing and NFO-induced membrane destabilization and lipid extraction. Here we provide a structural understanding of Aβ neurotoxicity via membrane interactions and aids the effort in understanding early events in Alzheimer’s disease and other neurodegenerative diseases.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Science Foundation (NSF); Univ. of New Mexico; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357; CHE-1834750; 1150855; 1605225; 1560058; ASERT-IRACDA-K12-GM088021; UNMCCC-P30-CA118100; UNM-CTSC-UL1-TR001449; NM-INBRE-P20-GM103451; 89233218CNA000001

OSTI ID:: 1599452

Alternate ID(s):: OSTI ID: 1776772

Report Number(s):: LA-UR-21-22944

Journal Information:: Langmuir, Vol. 35, Issue 48; ISSN 0743-7463

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 20 works

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References (52)

The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization Hamley, I. W. Chemical Reviews, Vol. 112, Issue 10 https://doi.org/10.1021/cr3000994	journal	June 2012
Differences between amyloid-β aggregation in solution and on the membrane: insights into elucidation of the mechanistic details of Alzheimer's disease Kotler, Samuel A.; Walsh, Patrick; Brender, Jeffrey R. Chem. Soc. Rev., Vol. 43, Issue 19 https://doi.org/10.1039/C3CS60431D	journal	January 2014
Membrane and surface interactions of Alzheimer’s Aβ peptide - insights into the mechanism of cytotoxicity: Membrane interactions of Alzheimer’s Aβ peptide Williams, Thomas L.; Serpell, Louise C. FEBS Journal, Vol. 278, Issue 20 https://doi.org/10.1111/j.1742-4658.2011.08228.x	journal	July 2011
Amyloid Precursor Protein Processing and Alzheimer's Disease O'Brien, Richard J.; Wong, Philip C. Annual Review of Neuroscience, Vol. 34, Issue 1 https://doi.org/10.1146/annurev-neuro-061010-113613	journal	July 2011
Amyloid beta amyloidosis in Alzheimerʼs disease Price, Donald L.; Sisodia, Sangram S.; Gandy, Samuel E. Current Opinion in Neurology, Vol. 8, Issue 4 https://doi.org/10.1097/00019052-199508000-00004	journal	January 1995
Two-Dimensional Structure of β-Amyloid(10−35) Fibrils ^† Benzinger, Tammie L. S.; Gregory, David M.; Burkoth, Timothy S. Biochemistry, Vol. 39, Issue 12 https://doi.org/10.1021/bi991527v	journal	March 2000
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril Wälti, Marielle Aulikki; Ravotti, Francesco; Arai, Hiromi Proceedings of the National Academy of Sciences, Vol. 113, Issue 34 https://doi.org/10.1073/pnas.1600749113	journal	July 2016
Physiological production of the β-amyloid protein and the mechanism of Alzheimer's disease Selkoe, Dennis J. Trends in Neurosciences, Vol. 16, Issue 10 https://doi.org/10.1016/0166-2236(93)90008-A	journal	October 1993
Unfolding the role of protein misfolding in neurodegenerative diseases Soto, Claudio Nature Reviews Neuroscience, Vol. 4, Issue 1 https://doi.org/10.1038/nrn1007	journal	January 2003
Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches Tsai, Julia; Grutzendler, Jaime; Duff, Karen Nature Neuroscience, Vol. 7, Issue 11 https://doi.org/10.1038/nn1335	journal	October 2004
Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease Meyer-Luehmann, Melanie; Spires-Jones, Tara L.; Prada, Claudia Nature, Vol. 451, Issue 7179 https://doi.org/10.1038/nature06616	journal	February 2008
Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis Kayed, R. Science, Vol. 300, Issue 5618 https://doi.org/10.1126/science.1079469	journal	April 2003
Structural differences between amyloid beta oligomers Breydo, Leonid; Kurouski, Dmitry; Rasool, Suhail Biochemical and Biophysical Research Communications, Vol. 477, Issue 4 https://doi.org/10.1016/j.bbrc.2016.06.122	journal	September 2016
Solution NMR Studies of the Aβ(1−40) and Aβ(1−42) Peptides Establish that the Met35 Oxidation State Affects the Mechanism of Amyloid Formation Hou, Liming; Shao, Haiyan; Zhang, Yongbo Journal of the American Chemical Society, Vol. 126, Issue 7 https://doi.org/10.1021/ja036813f	journal	January 2004
Fibrillar Oligomers Nucleate the Oligomerization of Monomeric Amyloid β but Do Not Seed Fibril Formation Wu, Jessica W.; Breydo, Leonid; Isas, J. Mario Journal of Biological Chemistry, Vol. 285, Issue 9 https://doi.org/10.1074/jbc.M109.069542	journal	December 2009
Molecular structural basis for polymorphism in Alzheimer's -amyloid fibrils Paravastu, A. K.; Leapman, R. D.; Yau, W. -M. Proceedings of the National Academy of Sciences, Vol. 105, Issue 47 https://doi.org/10.1073/pnas.0806270105	journal	November 2008
Protein Misfolded Oligomers: Experimental Approaches, Mechanism of Formation, and Structure-Toxicity Relationships Bemporad, Francesco; Chiti, Fabrizio Chemistry & Biology, Vol. 19, Issue 3 https://doi.org/10.1016/j.chembiol.2012.02.003	journal	March 2012
Oligomeric Intermediates in Amyloid Formation: Structure Determination and Mechanisms of Toxicity Fändrich, Marcus Journal of Molecular Biology, Vol. 421, Issue 4-5 https://doi.org/10.1016/j.jmb.2012.01.006	journal	August 2012
EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers Ehrnhoefer, Dagmar E.; Bieschke, Jan; Boeddrich, Annett Nature Structural & Molecular Biology, Vol. 15, Issue 6 https://doi.org/10.1038/nsmb.1437	journal	May 2008
Conformational Differences between Two Amyloid β Oligomers of Similar Size and Dissimilar Toxicity* Ladiwala, Ali Reza A.; Litt, Jeffrey; Kane, Ravi S. Journal of Biological Chemistry, Vol. 287, Issue 29 https://doi.org/10.1074/jbc.M111.329763	journal	July 2012
Fibril Fragmentation Enhances Amyloid Cytotoxicity Xue, Wei-Feng; Hellewell, Andrew L.; Gosal, Walraj S. Journal of Biological Chemistry, Vol. 284, Issue 49 https://doi.org/10.1074/jbc.M109.049809	journal	October 2009
Oligomeric and Fibrillar Species of Amyloid-β Peptides Differentially Affect Neuronal Viability Dahlgren, Karie N.; Manelli, Arlene M.; Stine, W. Blaine Journal of Biological Chemistry, Vol. 277, Issue 35 https://doi.org/10.1074/jbc.M201750200	journal	August 2002
Lipid membrane templates the ordering and induces the fibrillogenesis of Alzheimer's disease amyloid-β peptide: Lipid Membrane Templates Aβ Fibrillogenesis Chi, Eva Y.; Ege, Canay; Winans, Amy Proteins: Structure, Function, and Bioinformatics, Vol. 72, Issue 1 https://doi.org/10.1002/prot.21887	journal	January 2008
The Effect of Alzheimer’s Aβ Aggregation State on the Permeation of Biomimetic Lipid Vesicles Williams, Thomas L.; Day, Iain J.; Serpell, Louise C. Langmuir, Vol. 26, Issue 22 https://doi.org/10.1021/la101581g	journal	November 2010
Different effects of Alzheimer's peptide Aβ(1–40) oligomers and fibrils on supported lipid membranes Canale, Claudio; Seghezza, Silvia; Vilasi, Silvia Biophysical Chemistry, Vol. 182 https://doi.org/10.1016/j.bpc.2013.07.010	journal	December 2013
Soluble Amyloid Oligomers Increase Bilayer Conductance by Altering Dielectric Structure Sokolov, Yuri; Kozak, J. Ashot; Kayed, Rakez Journal of General Physiology, Vol. 128, Issue 6 https://doi.org/10.1085/jgp.200609533	journal	November 2006
Binding of protofibrillar Aβ trimers to lipid bilayer surface enhances Aβ structural stability and causes membrane thinning Dong, Xuewei; Sun, Yunxiang; Wei, Guanghong Phys. Chem. Chem. Phys., Vol. 19, Issue 40 https://doi.org/10.1039/C7CP05959K	journal	January 2017
Peptide–membrane interactions and mechanisms of membrane destruction by amphipathic α-helical antimicrobial peptides Sato, Hiromi; Feix, Jimmy B. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1758, Issue 9 https://doi.org/10.1016/j.bbamem.2006.02.021	journal	September 2006
The Interplay of Catalysis and Toxicity by Amyloid Intermediates on Lipid Bilayers: Insights from Type II Diabetes Hebda, James A.; Miranker, Andrew D. Annual Review of Biophysics, Vol. 38, Issue 1 https://doi.org/10.1146/annurev.biophys.050708.133622	journal	June 2009
Intrinsically disordered proteins drive membrane curvature Busch, David J.; Houser, Justin R.; Hayden, Carl C. Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms8875	journal	July 2015
Direct three-dimensional visualization of membrane disruption by amyloid fibrils Milanesi, L.; Sheynis, T.; Xue, W. -F. Proceedings of the National Academy of Sciences, Vol. 109, Issue 50 https://doi.org/10.1073/pnas.1206325109	journal	November 2012
Amyloid ion channels: A common structural link for protein-misfolding disease Quist, A.; Doudevski, I.; Lin, H. Proceedings of the National Academy of Sciences, Vol. 102, Issue 30 https://doi.org/10.1073/pnas.0502066102	journal	July 2005
Amyloid pores from pathogenic mutations Lashuel, Hilal A.; Hartley, Dean; Petre, Benjamin M. Nature, Vol. 418, Issue 6895 https://doi.org/10.1038/418291a	journal	July 2002
Multivariate Analyses of Amyloid-Beta Oligomer Populations Indicate a Connection between Pore Formation and Cytotoxicity Prangkio, Panchika; Yusko, Erik C.; Sept, David PLoS ONE, Vol. 7, Issue 10 https://doi.org/10.1371/journal.pone.0047261	journal	October 2012
Amyloid Ion Channels: A Porous Argument or a Thin Excuse? Eliezer, David Journal of General Physiology, Vol. 128, Issue 6 https://doi.org/10.1085/jgp.200609689	journal	November 2006
Two-Step Mechanism of Membrane Disruption by Aβ through Membrane Fragmentation and Pore Formation Sciacca, Michele F. M.; Kotler, Samuel A.; Brender, Jeffrey R. Biophysical Journal, Vol. 103, Issue 4 https://doi.org/10.1016/j.bpj.2012.06.045	journal	August 2012
Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes Ait-Bouziad, Nadine; Lv, Guohua; Mahul-Mellier, Anne-Laure Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01575-4	journal	November 2017
A partially folded structure of amyloid-beta(1–40) in an aqueous environment Vivekanandan, Subramanian; Brender, Jeffrey R.; Lee, Shirley Y. Biochemical and Biophysical Research Communications, Vol. 411, Issue 2 https://doi.org/10.1016/j.bbrc.2011.06.133	journal	July 2011
The Alzheimer’s Peptides Aβ40 and 42 Adopt Distinct Conformations in Water: A Combined MD / NMR Study Sgourakis, Nikolaos G.; Yan, Yilin; McCallum, Scott A. Journal of Molecular Biology, Vol. 368, Issue 5 https://doi.org/10.1016/j.jmb.2007.02.093	journal	May 2007
Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate Yang, Ting; Li, Shaomin; Xu, Huixin The Journal of Neuroscience, Vol. 37, Issue 1 https://doi.org/10.1523/JNEUROSCI.1698-16.2016	journal	November 2016
Soluble Amyloid-beta Aggregates from Human Alzheimer’s Disease Brains Esparza, Thomas J.; Wildburger, Norelle C.; Jiang, Hao Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep38187	journal	December 2016
Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers Kayed, Rakez; Head, Elizabeth; Sarsoza, Floyd Molecular Neurodegeneration, Vol. 2, Issue 1 https://doi.org/10.1186/1750-1326-2-18	journal	January 2007
Alzheimer’s amyloid fibrils: structure and assembly Serpell, Louise C. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1502, Issue 1 https://doi.org/10.1016/S0925-4439(00)00029-6	journal	July 2000
Local anesthetics and pressure: a comparison of dibucaine binding to lipid monolayers and bilayers Seelig, Anna Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 899, Issue 2 https://doi.org/10.1016/0005-2736(87)90400-7	journal	May 1987
Insertion of Alzheimer’s Aβ40 Peptide into Lipid Monolayers Ege, Canay; Lee, Ka Yee C. Biophysical Journal, Vol. 87, Issue 3 https://doi.org/10.1529/biophysj.104.043265	journal	September 2004
Collapse Mechanisms of Langmuir Monolayers Lee, Ka Yee C. Annual Review of Physical Chemistry, Vol. 59, Issue 1 https://doi.org/10.1146/annurev.physchem.58.032806.104619	journal	May 2008
The on-fibrillation-pathway membrane content leakage and off-fibrillation-pathway lipid mixing induced by 40-residue β-amyloid peptides in biologically relevant model liposomes Cheng, Qinghui; Hu, Zhi-Wen; Doherty, Katelynne E. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1860, Issue 9 https://doi.org/10.1016/j.bbamem.2018.03.008	journal	September 2018
Amyloid-β-Induced Ion Flux in Artificial Lipid Bilayers and Neuronal Cells: Resolving a Controversy Capone, Ricardo; Quiroz, Felipe Garcia; Prangkio, Panchika Neurotoxicity Research, Vol. 16, Issue 1 https://doi.org/10.1007/s12640-009-9033-1	journal	March 2009
Composition of phospholipids and of phospholipid fatty acids and aldehydes in human red cells Dodge, James T.; Phillips, Gerald B. Journal of Lipid Research, Vol. 8, Issue 6 https://doi.org/10.1016/S0022-2275(20)38890-8	journal	November 1967
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade Cline, Erika N.; Bicca, Maíra Assunção; Viola, Kirsten L. Journal of Alzheimer's Disease, Vol. 64, Issue s1 https://doi.org/10.3233/JAD-179941	journal	June 2018
Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death Arrasate, Montserrat; Mitra, Siddhartha; Schweitzer, Erik S. Nature, Vol. 431, Issue 7010 https://doi.org/10.1038/nature02998	journal	October 2004
Amyloid-β oligomers have a profound detergent-like effect on lipid membrane bilayers, imaged by atomic force and electron microscopy Bode, David C.; Freeley, Mark; Nield, Jon Journal of Biological Chemistry, Vol. 294, Issue 19 https://doi.org/10.1074/jbc.AC118.007195	journal	May 2019

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
monolayers
lipids
interfaces
peptides and proteins
membranes
Material science
Alzheimer’s disease
amyloid-beta (Aβ)
oligomer
membrane structure
toxicity
membrane-mediated fibrillation
lipid extraction
lipid packing
X-ray scattering

Title: Fibrillar and Nonfibrillar Amyloid Beta Structures Drive Two Modes of Membrane-Mediated Toxicity

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