AVS 51st International Symposium
    Biomaterial Interfaces Tuesday Sessions
       Session BI-TuA

Paper BI-TuA2
Binding and Aggregation of @alpha@-Synuclein on Supported Lipid Bilayers

Tuesday, November 16, 2004, 1:40 pm, Room 210D

Session: Biomembranes on a Chip
Presenter: J.S. Hovis, Purdue University
Authors: J.S. Hovis, Purdue University
E.A. Gamble, Purdue University
M.C. Hull, Purdue University
J.-C. Rochet, Purdue University
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Interest in @alpha@-synuclein was initiated with the observation that two mutations in the @alpha@-synuclein gene are linked to an early onset form of Parkinson's disease. @alpha@-Synuclein was further implicated in Parkinson's disease when the protein was found to be the main component of Lewy body inclusions in the brains of Parkinson's disease patients. In solution @alpha@-synuclein is natively unstructured while in the Lewy bodies it is primarily @beta@-sheet in character. It has been shown that @alpha@-synuclein readily binds lipid vesicles containing negatively charged lipids and that upon binding the protein adopts an @alpha@-helical conformation. Interestingly, the aggregation of @alpha@-synuclein into @beta@-sheet fibrils appears to be enhanced in the presence of negatively charged lipids. Due to the small size of the vesicles used in the previous studies the growth of the aggregates could not be observed directly. To provide more insight into the necessary conditions for the aggregation of @alpha@-synuclein we have observed the binding of @alpha@-synuclein to supported lipid bilayers using epi-fluorescence microscopy and infrared spectroscopy. The extent of aggregation was observed to depend on time, salt concentration, protein concentration and lipid composition. Results will be presented highlighting the necessary conditions for aggregation and comparing the conditions needed for wild-type aggregation with those of two mutant proteins (A30P and A53T) which have been linked with early onset Parkinson's.