Alpha-synuclein rich protein aggregates known as Lewy bodies are a pathogenic hallmark of Parkinson’s and many other neurodegenerative diseases. Biological studies suggest that changes in alpha-synuclein expression affect synaptic vesicle exocytosis and vesicle pooling, pointing toward a role in vesicle trafficking and neurotransmission. Furthermore, a collection of point mutations linked to hereditary Parkinson’s located within alpha-synuclein’s N-terminal lipid-binding region suggests that modulation of the protein/membrane interaction is related to disease development. In an attempt to approximate the biological complexity of real synaptic vesicles and gain insight into the impact of vesicle rigidity on alpha-synuclein/membrane interaction behaviors, we have synthesized a library of synaptic vesicle mimics composed of malleable lipid vesicles and rigid lipid-coated gold nanoparticles using a combination of DOPC, DOPE, DOPS, sphingomyelin obtained from brain extract and cholesterol. Synthesis and characterization of the mimic library will be discussed, including measurements of mimic size and surface charge by dynamic light scattering and zeta potential as well as confirmation of successful lipid-coating on gold nanoparticle cores by TEM imaging and absorbance measurements in the presence of excess potassium cyanide. Additionally, the actual ratio of lipids present in each mimic post-synthesis will be quantified prior to interaction studies with alpha-synuclein.

Complex lipid-coated gold nanoparticles for the study of alpha-synuclein/membrane interactions

ACS Spring 2022

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