Abstract
Alpha-synuclein (αS) is an extensively studied protein due to its involvement in a group of neurodegenerative disorders, including Parkinson′s disease, and its documented ability to undergo aberrant self-aggregation resulting in the formation of amyloid-like fibrils. In dilute solution, the protein is intrinsically disordered but can adopt multiple alternative conformations under given conditions, such as upon adsorption to nanoscale surfaces. The study of αS-nanoparticle interactions allows us to better understand the behavior of the protein and provides the basis for developing systems capable of mitigating the formation of toxic aggregates as well as for designing hybrid nanomaterials with novel functionalities for applications in various research areas. In this review, we summarize current progress on αS-nanoparticle interactions with an emphasis on the conformational plasticity of the biomolecule.
Highlights
Alpha-synuclein is a paradigmatic and one of the most extensively investigated intrinsically disordered proteins (IDPs) [1,2]
A number of studies have demonstrated that it is possible to determine and even predict how αS interacts with different nanoscale surfaces, highlighting the multiple conformations that the polypeptide can adopt and describing how to control the interactions
It has emerged that electrostatic forces dictate the mode of adsorption of monomeric αS to diverse nanoscale surfaces, providing alternative anchors for binding to negatively or positively charged NPs
Summary
Alpha-synuclein (αS) is a paradigmatic and one of the most extensively investigated intrinsically disordered proteins (IDPs) [1,2]. The variety of conformational states of certain disordered and self-aggregating proteins may be exploited to tune the properties of the hybrid material to different purposes. The review is divided into three sections discussing: (1) fundamental aspects and molecular determinants of αS adsorption onto NP surfaces; (2) efforts aimed at controlling αS self-aggregation, formation of toxic assemblies and disaggregation of insoluble fibrils; (3) achievements towards the fabrication of αS-based hybrid materials presenting novel functionalities. The selected case studies comprise both inorganic and organic materials as well as lipid nanovesicles While the former types are attractive tools for exploratory purposes and applications, the latter are included for their great relevance as biomembrane mimics to probe αS conformational versatility and membrane surface-induced structural transitions
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