Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge
Janson, Kevin; Zierath, Jennifer; Kyrilis, Fotis L.; Semchonok, Dmitry A.; Hamdi, Farzad; Skalidis, Ioannis; Kopf, Adrian H.; Das, Manabendra; Kolar, Cenek; Rasche, Marie; Vargas, Carolyn; Keller, Sandro; Kastritis, Panagiotis L.; Meister, Annette
(2021) Biochimica et Biophysica Acta - Biomembranes, volume 1863, issue 12, pp. 1 - 10
(Article)
Abstract
Certain amphiphilic copolymers form lipid-bilayer nanodiscs from artificial and natural membranes, thereby rendering incorporated membrane proteins optimal for structural analysis. Recent studies have shown that the amphiphilicity of a copolymer strongly determines its solubilization efficiency. This is especially true for highly negatively charged membranes, which experience pronounced Coulombic repulsion with
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polyanionic polymers. Here, we present a systematic study on the solubilization of artificial multicomponent lipid vesicles that mimic inner mitochondrial membranes, which harbor essential membrane-protein complexes. In particular, we compared the lipid-solubilization efficiencies of established anionic with less densely charged or zwitterionic and even cationic copolymers in low- and high-salt concentrations. The nanodiscs formed under these conditions were characterized by dynamic light scattering and negative-stain electron microscopy, pointing to a bimodal distribution of nanodisc diameters with a considerable fraction of nanodiscs engaging in side-by-side interactions through their polymer rims. Overall, our results show that some recent, zwitterionic copolymers are best suited to solubilize negatively charged membranes at high ionic strengths even at low polymer/lipid ratios.
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Keywords: DIBMA, Inner mitochondrial vesicles, Polymer nanodiscs, SMA, Transmission electron microscopy, Taverne, Biophysics, Biochemistry, Cell Biology
ISSN: 0005-2736
Publisher: Elsevier
Note: Funding Information: This study was funded by the Federal Ministry of Education and Research (BMBF, ZIK program) [grant numbers 03Z22HN23 and 03Z22HI2 (to P.L.K.)]; the European Regional Development Fund for Saxony-Anhalt [grant number EFRE: ZS/2016/04/78115 (to P.L.K.)], the International Graduate School AGRIPOLY supported by the European Regional Development Fund (ERDF) and the Federal State Saxony-Anhalt (A.M., P.L.K.), and the Martin Luther University Halle-Wittenberg . This work was partly funded by the Agence Nationale de la Recherche (ANR) and the DFG through the French–German FLUOR initiative (A.M.: ME 4165/2-1 and S.K.; KE 1478/7-1 ). This work was further supported financially by the Division of Chemical Sciences (CW) of the Netherlands Organisation for Scientific Research (NWO), via ECHO grant No. 711-017-006 (A.H.K.). We thank J.A. Killian for critical reading of the manuscript. Publisher Copyright: © 2021
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