Chiral Effect at Protein/Graphene Interface: A Bioinspired Perspective To Understand Amyloid Formation

Abstract

Protein misfolding to form amyloid aggregates is the main cause of neurodegenerative diseases. While it has been widely acknowledged that amyloid formation in vivo is highly associated with molecular surfaces, particularly biological membranes, how their intrinsic features, for example, chirality, influence this process still remains unclear. Here we use cysteine enantiomer modified graphene oxide (GO) as a model to show that surface chirality strongly influences this process. We report that R-cysteine modification suppresses the adsorption, nucleation, and fiber elongation processes of Aβ(1-40) and thus largely inhibits amyloid fibril formation on the surface, while S-modification promotes these processes. And surface chirality also greatly influences the conformational transition of Aβ(1-40) from α-helix to β-sheet. More interestingly, we find that this effect is highly related to the distance between chiral moieties and GO surface, and inserting a spacer group of about 1-2 nm between them prevents the adsorption of Aβ(1-40) oligomers, which eliminates the chiral effect. Detailed study stresses the crucial roles of GO surface. It brings novel insights for better understanding the amyloidosis process on surface from a biomimetic perspective.

Protein/Peptide Aggregation and Amyloidosis on Biointerfaces

“…From the insights of bionics, many compelling studies have shown the effect of chirality on the protein adsorption process [94,95,96] and even on cell behaviors [97,98]. In 2014, Sun et al showed that surface chirality might strongly influence the aggregation of A β (1–40) (Figure 6a) [41]. Utilizing cysteine (Cys) enantiomer-modified graphene oxide (GO) as a model platform, they monitored the amyloid formation process through ThT fluorescence spectroscopy and AFM.…”

“…Therefore, simplified interfaces such as or peptide- or amino acid-modified surfaces may be the ideal platform for further investigation. As described in Section 4, Sun et al [41,100] designed diverse chiral amino acid-modified surfaces and proposed the critical role of surface stereoselective interaction in A β aggregation. Lequin and Ongeri [116] designed a novel class of peptidomimetics composed of two hydrophobic dipeptides (Ala-Val and Val-Leu) linked to a d -glucopyranosyl scaffold.…”

“…( a ) Illustration of APP cleavage, A β misfolding and oligomer aggregation occurring on cell membranes [41]; ( b ) the cell membranes with complex components (i.e., carbohydrates, lipids, proteins, etc. ), structures and various surroundings; and ( c ) several main types of artificial biointerfaces developed from different perspectives to investigate the effects of interfacial properties on protein aggregation.…”

“…All the experiments were performed in the working solutions (100 µL) containing 25 µM A β (1–40) peptides, 25 µM ThT in phosphate buffer solution (50 mM, pH 7.4), and then 100 µL aqueous solution of various chiral GO samples (0.15 mg·mL ‒1 ) were added to the pre-prepared solutions, respectively. AFM images of R(S)-Cys-GO after incubation in A β (1–40) solutions (25 µM): ( c , f ) R-Cys-GO; ( d , g ) S-Cys-GO; and ( c , d ) R(S)-Cys-GO were added at the beginning of incubation; and ( f , g ) GO samples were added after 10 h of incubation at 37 °C [41]. ( a – g ) Adapted with permission.…”

Liposome/Graphene Oxide Interaction Studied by Isothermal Titration Calorimetry

“…For example, adsorption of nucleotides, nucleic acids, and proteins by GO was reported. [22][23][24] In this work, we employed ITC to study the adsorption between liposomes and GO.…”