Background: Protein-nanoparticle (NP) interactions dictate properties of nanoconjugates relevant to bionanotechnology. Non-covalent adsorption generates a protein corona (PC) formed by an inner and an outer layer, the hard and soft corona (HC, SC). Intrinsically disordered proteins (IDPs) exist in solution as conformational ensembles, whose response to the presence of NPs is not known. Methods: Three IDPs (α-casein, Sic1 and α-synuclein) and lysozyme are compared, describing conformational properties inside HC on silica NPs by circular dichroism (CD) and Fourier-transform infrared (FTIR) spectroscopy. Results: IDPs inside HC are largely unstructured, but display small, protein-specific conformational changes. A minor increase in helical content is observed for α-casein and α-synuclein, reminiscent of membrane effects on α-synuclein. Frozen in their largely disordered conformation, bound proteins do not undergo folding induced by dehydration, as they do in their free forms. While HC thickness approaches the hydrodynamic diameter of the protein in solution for lysozyme, it is much below the respective values for IDPs. NPs boost α-synuclein aggregation kinetics in a dose-dependent manner. Conclusions: IDPs maintain structural disorder inside HC, experiencing minor, protein-specific, induced folding and stabilization against further conformational transitions, such as formation of intermolecular beta-sheets upon dehydration. The HC is formed by a single layer of protein molecules. SC likely plays a key role stabilizing amyloidogenic α-synuclein conformers. General significance: Protein-NP interactions can mimic those with macromolecular partners, allowing dissection of contributing factors by rational design of NP surfaces. Application of NPs in vivo should be carefully tested for amyloidogenic potential.
|Titolo:||Conformational properties of intrinsically disordered proteins bound to the surface of silica nanoparticles|
|Autori:||Vitali, Michele; Rigamonti, Valentina; Natalello, Antonino; Colzani, Barbara; Avvakumova, Svetlana; Brocca, Stefania; Santambrogio, Carlo; Narkiewicz, Joanna; Legname, Giuseppe; Colombo, Miriam; Prosperi, Davide; Grandori, Rita|
|Data di pubblicazione:||2018|
|Digital Object Identifier (DOI):||10.1016/j.bbagen.2018.03.026|
|Fulltext via DOI:||https://doi.org/10.1016/j.bbagen.2018.03.026|
|Appare nelle tipologie:||1.1 Journal article|