Abstract
Protein/Peptide amyloidosis is the main cause of several diseases, such as neurodegenerative diseases. It has been widely acknowledged that the unnatural fibrillation of protein/peptides in vivo is significantly affected by the physical and chemical properties of multiscale biological membranes. For example, previous studies have proved that molecule chirality could greatly influence the misfolding, fibrillation and assembly of β-Amyloid peptides at the flat liquid-solid surface. However, how the nanoscale chirality influences this process remains unclear. Here we used gold nanoparticles (AuNPs, d = 4 ± 1 nm)—modified with N-isobutyl-L(D)-cysteine (L(D)-NIBC) enantiomers—as a model to illustrate the chiral effect on the amylin fibrillation at nano-bio interface. We reported that both two chiral AuNPs could inhibit amylin fibrillation in a dosage-dependent manner but the inhibitory effect of L-NIBC-AuNPs was more effective than that of D-NIBC-AuNPs. In-situ real time circular dichroism (CD) spectra showed that L-NIBC-AuNPs could inhibit the conformation transition process of amylin from random coils to α-helix, while D-NIBC-AuNPs could only delay but not prevent the formation of α-helix; however, they could inhibit the further conformation transition process of amylin from α-helix to β-sheet. These results not only provide interesting insight for reconsidering the mechanism of peptides amyloidosis at the chiral interfaces provided by biological nanostructures in vivo but also would help us design therapeutic inhibitors for anti-amyloidosis targeting diverse neurodegenerative diseases.
Highlights
Protein/peptides amyloidosis is tightly associated with a variety of causes of diseases [1,2], such as neurodegenerative diseases [3,4,5,6]
More and more evidences have indicated that the multiscale biological membranes in vivo provide a larger number of reactive sites to interact with dissociative protein/peptides [8,9,10,11], which play a key procedure for their accumulation and fibrillation at very low concentrations [12,13,14]
When 10 μmol·L−1 amylin co-incubated with 20 mg·L−1 L(D)-NIBC-AuNPs, amylin monomers or oligomers would be absorbed rapidly onto the surface of both two chiral AuNPs via electrostatic interaction, leading to the initial zeta potential of both two mixtures appearing at +4.9 mV
Summary
Protein/peptides amyloidosis is tightly associated with a variety of causes of diseases [1,2], such as neurodegenerative diseases [3,4,5,6]. We have reported the size effect of interfaces on Aβ peptides aggregation and fibrillation [26]. These inspired us to introduce the molecule chirality onto the nano-bio interfaces to stuNdaynomthateerciahlsi2r0a1l9,e9f,fxeFcOt RonPEpERroRtEeViInEWamyloidosis. L(D)-NIBC (3.2 mg) was introduced to the mixture of HAuCl4 (0.2 mL, 25 mmol·L−1, in methanol) and acetic acid (0.05 mL) under vigorous stirring in the ice bath. The solution in the centrifuge tube was discarded to remove the large-sized gold nanoparticles and the solution in the filter device and water was added to the centrifuge tube for centrifugation separates, repeated for three times. The lyophilized powders were stored at 4 ◦C for the following experiments
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