Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge

Kevin Janson, Jennifer Zierath, Fotis L. Kyrilis, Dmitry A. Semchonok, Farzad Hamdi, Ioannis Skalidis, Adrian H. Kopf, Manabendra Das, Cenek Kolar, Marie Rasche, Carolyn Vargas, Sandro Keller, Panagiotis L. Kastritis*, Annette Meister

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Article number183725
Pages (from-to)1-10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1863
Issue number12
DOIs
Publication statusPublished - 1 Dec 2021

Keywords

  • DIBMA
  • Inner mitochondrial vesicles
  • Polymer nanodiscs
  • SMA
  • Transmission electron microscopy

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