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Abstract
Alpha-Synuclein (aSyn) is an intrinsically disordered neuronal protein that forms an amphipathic helix when it peripherally binds to lipid membranes. This protein is associated with Parkinson’s Disease (PD) and despite decades of research, the physiological function of aSyn is still not entirely understood. The evidence strongly supports the interaction of aSyn with neuronal membranes to be integral to its function, motivating the careful study of its membrane-binding behavior. Thus, this thesis aims to understand this interaction in greater detail through understanding how the binding modes of the protein change with lipid composition and PD-associated mutants, and how other physiologically relevant properties such as protein concentration, osmotic stress, and calcium ions affect the membrane binding behavior. Overall, we demonstrate that even small changes in membrane properties can have downstream effects that could be physiologically relevant.