Skip to main content

Model Phospholipid Liposomes to Study the β-Amyloid-Peptide-Induced Membrane Disruption

  • Protocol
  • First Online:
Peptide Self-Assembly

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1777))

Abstract

Model phospholipid liposomes have been utilized widely to study the molecular interactions between peptides and membrane bilayers. In the mechanistic study of Alzheimer’s disease (AD), disruption of neuronal cell membranes has been considered as a major contribution for the β-amyloid (Aβ) peptides’ neurotoxicity. However, clear interpretation of the Aβ-induced cellular membrane at high-resolution level is challenging because of the co-existence of multiple pathways. Here we present the generation of simplified model liposome systems that will facilitate the in-depth mechanistic studies. Protocols for the preparation of model liposomes and the characterization of individual membrane disruption effects will be described.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Reference

  1. Williams TL, Serpell LC (2011) Membrane and surface interactions of Alzheimer’s Abeta peptide—insights into the mechanism of cytotoxicity. FEBS J 278:3905–3917

    Article  CAS  Google Scholar 

  2. Qiang W, Kelley K, Tycko R (2013) Polymorph-specific kinetics and thermodynamics of beta-amyloid fibril growth. J Am Chem Soc 135(18):6860–6871

    Article  CAS  Google Scholar 

  3. Sengupta P, Garai K, Sahoo B, Shi Y, Callaway DJ, Maiti S (2003) The amyloid beta peptide (Abeta(1-40)) is thermodynamically soluble at physiological concentrations. Biochemistry 42(35):10506–10513

    Article  CAS  Google Scholar 

  4. Hasegawa K, Ono K, Yamada M, Naiki H (2002) Kinetic modeling and determination of reaction constants of Alzheimer’s beta-amyloid fibril extension and dissociation using surface plasmon resonance. Biochemistry 41(46):13489–13498

    Article  CAS  Google Scholar 

  5. Bokvist M, Lindstrom F, Watts A, Grobner G (2004) Two types of Alzheimer’s beta-amyloid (1-40) peptide membrane interactions: aggregation preventing transmembrane anchoring versus accelerated surface fibril formation. J Mol Biol 335:1039–1049

    Article  CAS  Google Scholar 

  6. Sciacca MF, Kotler SA, Brender JR, Chen J, Lee DK, Ramamoorthy A (2012) Two-step mechanism of membrane disruption by Abeta through membrane fragmentation and pore formation. Biophys J 103(4):702–710

    Article  CAS  Google Scholar 

  7. Qiang W, Yau WM, Schulte J (2015) Fibrillation of beta amyloid peptides in the presence of phospholipid bilayers and the consequent membrane disruption. Biochim Biophys Acta Biomembr 1848(1):266–276

    Article  CAS  Google Scholar 

  8. Sparr E, Engel MFM, Sakharov DV, Sprong M, Jacobs J, de Kruijff B, Hoppener JWH, Killian JA (2004) Islet amyloid polypeptide-induced membrane leakage involves uptake of lipids by forming amyloid fibers. FEBS Lett 577:117–120

    Article  CAS  Google Scholar 

  9. Quist A, Doudevski I, Lin H, Azimova R, Ng D, Frangione B, Kagan B, Ghiso J, Lal R (2005) Amyloid ion channels: a common sturctural link for protein-misfolding disease. Proc Natl Acad Sci 102(30):10427–10432

    Article  CAS  Google Scholar 

  10. Connelly L, Jang H, Arce FT, Ramachandran S, Kagan BL, Nussinov R, Lal R (2012) Effects of point substitutions on the structure of toxic Alzheimer’s beta-amyloid channels: atomic force microscopy and molecular dymanics simulations. Biochemistry 51(14):3031–3038

    Article  CAS  Google Scholar 

  11. Lal R, Lin H, Quist AP (2007) Amyloid beta ion channel: 3D structure and relevance to amyloid channel paradigm. Biochim Biophys Acta 1768(8):1966–1975

    Article  CAS  Google Scholar 

  12. Delgado DA, Doherty KE, Cheng Q, Kim H, Xu D, Dong H, Grewer CT, Qiang W (2016) Distinct membrane disruption pathways induced by the 40-residue beta-amyloid peptides. J Biol Chem 291(23):12233–12244

    Article  CAS  Google Scholar 

  13. Akinlolu RD, Nam M, Qiang W (2015) Competition between fibrillation and induction of vesicle fusion for the membrane-associated 40-residue b amyloid peptides. Biochemistry 54(22):3416–3419

    Article  CAS  Google Scholar 

  14. Qiang W, Akinlolu RD, Nam M, Shu N (2014) Strcutral evolution and membrane interaction of the 40-residue beta amyloid peptides: differences in the initial proximity between peptides and the membrane bilayer studied by solid-state nulear magnetic resonance spectroscopy. Biochemistry 53(48):7503–7514

    Article  CAS  Google Scholar 

  15. Qiang W, Yau WM, Tycko R (2011) Structural evolution of Iowa mutant b-amyloid fibrils from polymorphic to homogeneous states under repeated seeded growth. J Am Chem Soc 133(11):4018–4029

    Article  CAS  Google Scholar 

  16. Vestergaard MC, Morita M, Hamada T, Takagi M (2013) Membrane fusion and vesicular transformation induced by Alzheimer’s amyloid beta. Biochim Biophys Acta 1828(4):1314–1321

    Article  CAS  Google Scholar 

  17. Qiang W, Sun Y, Weliky DP (2009) A strong correlation between fusogenicity and membrane insertion depth of the HIV fusion peptide. Proc Natl Acad Sci 106(36):15314–15319

    Article  CAS  Google Scholar 

  18. Yang R, Prorok M, Castellino FJ, Weliky DP (2004) A trimeric HIV-1 fusion peptide construct which does not self-associate in aqueous solution and which has 15-fold higher membrane fusion rate. J Am Chem Soc 126(45):14722–14723

    Article  CAS  Google Scholar 

  19. Lin H, Bhatia R, Lal R (2001) Amyloid beta protein forms ion channels: implications for Alzheimer’s disease pathophysiology. FASEB J 15:2433–2444

    Article  CAS  Google Scholar 

  20. Ostroumova OS, Schagina LV, Mosevitsky MI, Zakharov VV (2010) Ion channel activity of brain abundant protein BASP1 in planar lipid bilayers. FEBS J 278(3):461–469

    Article  Google Scholar 

  21. Delgado DA, Doherty K, Cheng Q, Kim H, Xu D, Dong H, Grewer C, Qiang W (2016) Distinct membrane disruption pathways are induced by the 40-residue Î2-amyloid peptides. J Biol Chem 291(23):12233–12244

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by the start-up funding from the Research Foundation of the State University of New York. We acknowledge Dr. He Dong and Mr. Dawei Xu from Clarkson University, and Dr. Christof Grewer from Binghamton University for their kind helps on fluorescence imaging and electrophysiological current measurements.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wei Qiang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Qiang, W., Doherty, K.E. (2018). Model Phospholipid Liposomes to Study the β-Amyloid-Peptide-Induced Membrane Disruption. In: Nilsson, B., Doran, T. (eds) Peptide Self-Assembly. Methods in Molecular Biology, vol 1777. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7811-3_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7811-3_23

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7809-0

  • Online ISBN: 978-1-4939-7811-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics