title: Membrane remodeling and mechanics: Experiments and simulations of α-Synuclein.
abstract: We review experimental and simulation approaches that have been used to determine curvature generation and remodeling of lipid bilayers by membrane-bending proteins. Particular emphasis is placed on the complementary approaches used to study α-Synuclein (αSyn), a major protein involved in Parkinson's disease (PD). Recent cellular and biophysical experiments have shown that the protein 1) deforms the native structure of mitochondrial and model membranes; and 2) inhibits vesicular fusion. Today's advanced experimental and computational technology has made it possible to quantify these protein-induced changes in membrane shape and material properties. Collectively, experiments, theory and multi-scale simulation techniques have established the key physical determinants of membrane remodeling and rigidity: protein binding energy, protein partition depth, protein density, and membrane tension. Despite the exciting and significant progress made in recent years in these areas, challenges remain in connecting biophysical insights to the cellular processes that lead to disease. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 312 Church St. SE, Minneapolis, MN 55455, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: West
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 312 Church St. SE, Minneapolis, MN 55455, USA.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Brummel
authors.affiliation: Department of Neuroscience, University of Minnesota, 321 Church St. SE, Minneapolis, MN 55455, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Braun
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 S 34th St., Philadelphia, PA 19104, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rhoades
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 312 Church St. SE, Minneapolis, MN 55455, USA. Electronic address: jnsachs@umn.edu.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Sachs
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods; D051844:alpha-Synuclein / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D051844:alpha-Synuclein
keywords: Bilayer rigidity; Coarse-grained molecular dynamics (CGMD); Membrane curvature; Parkinson's disease; Synaptic vesicles; Tubulation; α-Synuclein