In vitro study of magnetite-amyloid β complex formation

doi:10.1016/j.nano.2011.11.010

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 8, Issue 6, August 2012, Pages 974-980

https://doi.org/10.1016/j.nano.2011.11.010 Get rights and content

Abstract

Biogenic magnetite (Fe₃O₄) has been identified in human brain tissue. However, abnormal concentration of magnetite nanoparticles in the brain has been observed in different neurodegenerative pathologies. In the case of Alzheimer's disease (AD), these magnetic nanoparticles have been identified attached to the characteristic brain plaques, which are mainly formed by fibrils of amyloid β peptide (Aβ). However, few clues about the formation of the magnetite-Aβ complex have been reported. We have investigated the interaction between these important players in AD with superconducting quantum interference, scanning electron microscope, surface plasmon resonance, and magnetic force microscopy. The results support the notion that the magnetite-Aβ complex is created before the synthesis of the magnetic nanoparticles, bringing a highly stable interaction of this couple.

From the Clinical Editor

This paper describes the association of magnetite nanoparticles and Aβ in vitro. Given the number and impact of neurodegenerative diseases associated with β amyloid deposition, future in vitro and in vivo applications are expected to lead to an enhanced understanding of these important and as of yet generally incurable diseases.

Graphical Abstract

Abnormal concentration of magnetite nanoparticles in the brain has been observed in different neurodegenerative pathologies. In the case of Alzheimer's disease (AD), these magnetic nanoparticles have been identified attached to the fibrils of amyloid β peptide (Aβ). However, few clues about the formation of the magnetite-Aβ complex have been reported. This work represents a first approach to study the association of magnetite nanoparticles and Aβ in vitro.

Iron can adopt both the ferric (Fe³⁺) and ferrous (Fe²⁺) valence states in vivo. The ability to change from one state to the other confers a very important role on iron in different biological oxidation and transport processes. However, the disruption of the normal iron metabolism can entail harmful consequences because Fe³⁺ and, especially, Fe²⁺ generate toxic free radicals mainly via the Fenton reaction.

Section snippets

Materials

Iron (II) chloride tetrahydrate, iron (III) chloride hexahydrate, ammoniumhydroxide, monoclonal anti-Aβ (13-28) antibody, and phosphate buffered saline (PBS) were purchased from Sigma-Aldrich (St. Louis, Missouri). Amyloid β peptide 1-42 (Aβ₄₂) was supplied by EZ-Biolab (Carmel, Indiana).

Magnetite-Aβ₄₂ complex synthesis

Lyophilized Aβ₄₂ (1 mg) was efficiently dissolved in 250 μL of 1,1,1,3,3,3 hexafluoro-2-propanol and divided in aliquots, which were lyophilized with an Eppendorf Concentrator 5301 vacuum centrifuge for 30

Characterization of magnetite-Aβ₄₂ complex with SQUID

The magnetic nanoparticles synthesized are mainly a mixture of magnetite (Fe₃O₄) and maghemite (Fe₂O₃). These nanoparticles alternate lattices of Fe²⁺ and Fe³⁺ with different unpaired electron spins, which give to these iron oxides its ferromagnetic feature.

SQUID measures the magnetic susceptibility of materials to an applied alternated current (AC) magnetic field. This relation is presented in the next equation: $M = χ H$

where M is the magnetization, H the magnetic field strength, and χ is the

Discussion

In this work a study of the origin of the magnetite-Aβ₄₂ interaction, two relevant key players in diseased brain tissue of Alzheimer pathology, was carried out with SQUID, SEM, SPR, and MFM.

SQUID results demonstrate the strong interaction between the magnetite nanoparticles and Aβ₄₂ peptide after some magnetic washing steps for removing unbound peptide, and the magnetization of these nanoparticles even attached to the peptide. The diameter distribution of the synthesized magnetic nanoparticles

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: The authors have no conflict of interest and/or commercial associations, current and within the past 5 years that might pose a potential, perceived, or real conflict of interest.

: This research has been financed by CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The Nanobioengineering group has support from the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2009 SGR 505). This study was also supported by the “Fundación M. Botín”, Santander, Spain and J.J.V.-D. and X.F.-B. were supported by grant 2009SGR-760 from the Generalitat de Catalunya.

¹: M.M. and I.B. contributed equally to this study.

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Research ArticleIn vitro study of magnetite-amyloid β complex formation

Abstract

From the Clinical Editor

Graphical Abstract

Section snippets

Materials

Magnetite-Aβ42 complex synthesis

Characterization of magnetite-Aβ42 complex with SQUID

Discussion

Lancet Neurol

Free Radic Biol Med

J Struct Biol

J Struct Biol

Scr Mater

J Magn Magn Mater

Neurobiol Dis

J Biol Chem

Anal Biochem