Ana West1, Benjamin E Brummel1, Anthony R Braun2, Elizabeth Rhoades3, Jonathan N Sachs4. 1. Department of Biomedical Engineering, University of Minnesota, 312 Church St. SE, Minneapolis, MN 55455, USA. 2. Department of Neuroscience, University of Minnesota, 321 Church St. SE, Minneapolis, MN 55455, USA. 3. Department of Chemistry, University of Pennsylvania, 231 S 34th St., Philadelphia, PA 19104, USA. 4. Department of Biomedical Engineering, University of Minnesota, 312 Church St. SE, Minneapolis, MN 55455, USA. Electronic address: jnsachs@umn.edu.
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.
We review experimental and simulation approaches that have been used to determine curvature genen class="Species">ration and remodeling of n>n class="Chemical">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: Ana West; Valeria Zoni; Walter E Teague; Alison N Leonard; Stefano Vanni; Klaus Gawrisch; Stephanie Tristram-Nagle; Jonathan N Sachs; Jeffery B Klauda Journal: J Phys Chem B Date: 2020-01-22 Impact factor: 2.991
Authors: Anthony R Braun; Michael M Lacy; Vanessa C Ducas; Elizabeth Rhoades; Jonathan N Sachs Journal: J Membr Biol Date: 2017-02-26 Impact factor: 1.843
Authors: Justin T Marinko; Hui Huang; Wesley D Penn; John A Capra; Jonathan P Schlebach; Charles R Sanders Journal: Chem Rev Date: 2019-01-04 Impact factor: 60.622