title: Adsorption of alpha-synuclein on lipid bilayers: modulating the structure and stability of protein assemblies.
abstract: The interaction of alpha-synuclein with phospholipid membranes has been examined using supported lipid bilayers and epi-fluorescence microscopy. The membranes contained phosphatidylcholine (PC) and phosphatidic acid (PA), which mix at physiological pH. Upon protein adsorption, the lipids undergo fluid-fluid phase separation into PC-rich and PA-rich regions. The protein preferentially adsorbs to the PA-rich regions. The adsorption and subsequent aggregation of alpha-synuclein was probed by tuning several parameters: the charge on the lipids, the charge on the protein, and the screening environment. Conditions which promoted the greatest extent of adsorption resulted in structurally heterogeneous aggregates, while comparatively homogeneous aggregates were observed under conditions whereby adsorption did not occur as readily. Our observation that different alterations to the system lead to different degrees of aggregation and different aggregate structures poses a challenge for drug discovery. Namely, therapies aimed at neutralizing alpha-synuclein must target a broad range of potentially toxic, membrane-bound assemblies.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Farzin
authors.initials: F
authors.lastname: Haque
authors.forename: Anjan P
authors.initials: AP
authors.lastname: Pandey
authors.forename: Lee R
authors.initials: LR
authors.lastname: Cambrea
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rochet
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Hovis
mesh_terms: D000327:Adsorption; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D055550:Protein Stability; D013816:Thermodynamics; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D051844:alpha-Synuclein