Probing the modulated formation of gold nanoparticles–beta-lactoglobulin corona complexes and their applications

Abstract

Understanding interactions between proteins and nanoparticles (NPs) along with the underlying structural and dynamic information is of utmost importance to exploit nanotechnology for biomedical applications. Upon adsorption onto the NP surface, proteins form a well-organized layer that dictates the identity of the NP-protein complex named corona and governs its biological pathways. Given the high biological relevance, in-depth molecular investigations and applications of NPs-protein corona complexes are still scarce, especially since different proteins form unique patterns of corona and hence identification of biomolecular motifs at the interface is critical. In this work, we provide molecular insights and structural characterizations of the bionano interface of a popular food-based protein, bovine beta-lactoglobulin (β-LG), with gold nanoparticles (AuNPs) and the formation of corona complexes by combined molecular simulations and complementary experiments. Two major binding sites in β-LG were identified to be driven by citrate-mediated electrostatic interactions, while the associated binding kinetics and conformational changes in secondary structures were also characterized. More importantly, the superior stability of the corona led us to further explore its biomedical applications with examples of smart-phone based point-of-care biosensing of Escherichia coli (E. coli) and computed tomography (CT) of gastrointestinal (GI) tract through oral administration to probe GI tolerance and functions. Considering the biocompatibility, edible nature and efficient excretion through defecation, AuNPs-β-LG corona complexes have shown promising perspectives in future in vitro and in vivo clinical settings.

Monosaccharide-Mediated Rational Synthesis of a Universal Plasmonic Platform With Broad Spectral Fluorescence Enhancement For High-Sensitivity Cancer Biomarker Analysis

“…Proteins like albumins are exhaustively documented to have high binding a nities to metals and form corona layers 30,34 , which are an ideal model probe to provide an appropriate distance for enhancement and prevent uorophores in close proximity to the plasmonic surface from quenching. Using uorophorelabeled BSA, we scrutinized the macroscopic enhancement on a broad spectral range of uorescence across the visible window (Fig.…”

“…It is then interrogated whether the uorescence enhancement of AgNIS was due to broad spectral surface plasmon resonance, rather than merely more surface-absorbed molecules, on the grounds that AgNIS could have a slightly larger effective surface area as well as notable protein-nanostructure interactions 30 .…”

“…AgNIS was synthesized through a two-step surface-based seed-mediated growth, using a modi ed silver redox reaction with AuNPs as catalysts and nucleation centers 29 . First, AuNPs were synthesized using a modi ed Turkevich method 30,31 . Succinctly, 15 mL 1% w/w sodium citrate was added to 100 mL 1 mM HAuCl 4 for 15 min of boiling.…”

Molecular Modeling of Protein Corona Formation and Its Interactions with Nanoparticles and Cell Membranes for Nanomedicine Applications

“…They also found that the HSA-AuNP binding induces the flexibility and structural changes of HSA, which allosterically influences the binding affinity of HSA to fatty acids, thyroxin, and metals [ 24 ]. Yang et al simulated beta-lactoglobulin that was bound to AuNP and determined its binding site and structural change, which are interpreted by electrostatic interactions [ 25 ]. Tollefson et al simulated cytochrome c that was bound to a mercaptopropionic acid-functionalized AuNP and determined the preferred binding orientations of adsorbed proteins ( Figure 2 ) [ 26 ].…”

Molecular Modeling for Nanomaterial–Biology Interactions: Opportunities, Challenges, and Perspectives

“…The literature offers several examples of MD simulations of protein adsorption on different materials, such as graphene sheets (Chong et al, 2015), carbon nanotubes (Ge et al, 2011; Gu et al, 2015), gold nanoparticles/surfaces (Wang et al, 2013; Brancolini et al, 2014; Tavanti et al, 2015; Bellucci et al, 2016; Yang et al, 2017; Ma et al, 2018), hydroxyapatite surfaces (Dong et al, 2007, 2011), fullerenes (Leonis et al, 2015), titanium oxide surfaces (Utesch et al, 2011; Mudunkotuwa and Grassian, 2014), and molybdenum disulfide (Gu et al, 2018), highlighting the specific interactions behind the binding and the attainment of structural changes. Interestingly, there are no relevant computational studies of protein adsorption on polymer surfaces.…”