Effect of Fe₃O₄magnetic nanoparticles on lysozyme amyloid aggregation

Abstract

Peptide amyloid aggregation is a hallmark of several human pathologies termed amyloid diseases. We have investigated the effect of electrostatically stabilized magnetic nanoparticles of Fe(3)O(4) on the amyloid aggregation of lysozyme, as a prototypical amyloidogenic protein. Thioflavin T fluorescence assay and atomic force microscopy were used for monitoring the inhibiting and disassembly activity of magnetic nanoparticles of Fe(3)O(4). We have found that magnetic Fe(3)O(4) nanoparticles are able to interact with lysozyme amyloids in vitro leading to a reduction of the amyloid aggregates, thus promoting depolymerization; the studied nanoparticles also inhibit lysozyme amyloid aggregation. The ability to inhibit lysozyme amyloid formation and promote lysozyme amyloid disassembly exhibit concentration-dependent characteristics with IC50 = 0.65 mg ml(-1) and DC50 = 0.16 mg ml(-1) indicating that nanoparticles interfere with lysozyme aggregation already at stoichiometric concentrations. These features make Fe(3)O(4) nanoparticles of potential interest as therapeutic agents against amyloid diseases and their non-risk exploitation in nanomedicine and nanodiagnostics.

Nanoparticles in relation to peptide and protein aggregation

“…81 Various techniques (thioflavin T-binding assay, TEM, and surface plasmon resonance) are used to investigate the nanoparticle's ability to interact with proteins during fibrillogenesis. 82,83 The interaction between thioflavin-T with amyloid fibrils causes a red shift in emission spectra, but no response is observed in the presence of soluble proteins, oligomers, or amorphous aggregates. 82,83 Circular dichroism and photoluminescence are other important techniques that are used to investigate the inhibition of the fibrillation process, as these techniques provide a kinetic shift towards unfolded regions and make a clear distinction between protein secondary and tertiary structures.…”

“…82,83 The interaction between thioflavin-T with amyloid fibrils causes a red shift in emission spectra, but no response is observed in the presence of soluble proteins, oligomers, or amorphous aggregates. 82,83 Circular dichroism and photoluminescence are other important techniques that are used to investigate the inhibition of the fibrillation process, as these techniques provide a kinetic shift towards unfolded regions and make a clear distinction between protein secondary and tertiary structures. 84 Moreover, using a crystallographic model, Heldt et al 85 provided the first evidence that insulin amyloid fibril formation occurs predominately unidirectionally, demonstrating that it may be asymmetric and propagate mostly in one direction.…”

Effect of iron oxide loading on magnetoferritin structure in solution as revealed by SAXS and SANS

“…In particular, the interaction of various nanoparticles with specific protein aggregates (amyloids) can be mentioned. Among different types of probed materials [35] magnetic nanoparticles of iron oxides show inhibiting and even disaggregating effect on amyloidal aggregation [36][37][38][39][40].…”

Characterization of Fe3O4Magnetic Nanoparticles Modified with Dextran and Investigation of Their Interaction with Protein Amyloid Aggregates

“…Due to their special characteristics, they have gradually gained importance in numerous biological fields. Recently it has been found that Fe 3 O 4 magnetic nanoparticles (MNPs) are able to interact with lysozyme amyloid aggregates [1].…”