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. 2013 Mar 20;4(3):475-85.
doi: 10.1021/cn300196n. Epub 2013 Jan 23.

Influence of the physiochemical properties of superparamagnetic iron oxide nanoparticles on amyloid β protein fibrillation in solution

Morteza Mahmoudi  1 , Fiona Quinlan-Pluck, Marco P Monopoli, Sara Sheibani, Hojatollah Vali, Kenneth A Dawson, Iseult Lynch
Affiliations

Influence of the physiochemical properties of superparamagnetic iron oxide nanoparticles on amyloid β protein fibrillation in solution

Morteza Mahmoudi et al. ACS Chem Neurosci. .

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as promising nanodiagnostic materials due to their biocompatibility, unique magnetic properties, and their application as multimodal contrast agents. As coated SPIONs have potential use in the diagnosis and treatment of various brain diseases such as Alzheimer's, a comprehensive understanding of their interactions with Aβ and other amyloidogenic proteins is essential prior to their clinical application. Here we demonstrate the effect of thickness and surface charge of the coating layer of SPIONs on the kinetics of fibrillation of Aβ in aqueous solution. A size and surface area dependent "dual" effect on Aβ fibrillation was observed. While lower concentrations of SPIONs inhibited fibrillation, higher concentrations increased the rate of Aβ fibrillation. With respect to coating charge, it is evident that the positively charged SPIONs are capable of promoting fibrillation at significantly lower particle concentrations compared with negatively charged or uncharged SPIONs. This suggests that in addition to the presence of particles, which affect the concentration of monomeric protein in solution (and thereby the nucleation time), there are also effects of binding on the protein conformation.

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Figures

Figure 1
Figure 1
Scheme showing the how the various single- and double-coated SPIONs were prepared. Note that, in the case of the plain particles, the second coating layer was not very successful.
Figure 2
Figure 2
(a,b) TEM images (scale bar = 50 nm) of single- and double-coated SPIONs with the COOH-dextran coating (upper left panels are selected area diffraction pattern) and their corresponding energy dispersive X-ray spectroscopy results. (c, d) TEM images of single- and double-coated SPIONs with the COOH-dextran coating with higher magnification; there is clear evidence of aggregation of SPIONs in (d) explaining the larger size, as also measured in DLS.
Figure 3
Figure 3
Kinetics of aggregation of Aβ in the absence or presence of various single and double (negative, positive, and plain) dextran-coated SPIONs at different SPION concentrations including (a) 40 μg/mL, (b) 60 μg/mL, (c) 80 μg/mL, and (d) 100 μg/mL.
Figure 4
Figure 4
TEM images of Aβ fibrils after incubation for (a) 700 min, (b) 1200 min, and (c) 2400 min in the absence of SPIONs. Protein concentration is 0.5 μM.
Figure 5
Figure 5
TEM images of Aβ fibrils after 2400 min incubation of Aβ monomers (0.5 μM) with double layer negative (left), plain (middle), and positive (right) dextran-coated SPIONs (100 μg/mL) at two different magnifications. In the case of the positively charged dextran-coated SPIONs, only very small fibrils are observed (see red arrows).
Figure 6
Figure 6
Circular dichroism signatures obtained for Aβ (0.5 μM), alone after 100 min and 1340 min incubation, and for mixtures of Aβ and all types of dextran-coated SPIONs (100 μg/mL) after 1340 min.
See this image and copyright information in PMC

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