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

doi:10.1016/j.bbamem.2021.183725

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 journal › Article › Academic › peer-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 language	English
Article number	183725
Pages (from-to)	1-10
Journal	Biochimica et Biophysica Acta - Biomembranes
Volume	1863
Issue number	12
DOIs	https://doi.org/10.1016/j.bbamem.2021.183725
Publication status	Published - 1 Dec 2021

Bibliographical 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

Funding

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.

Keywords

DIBMA
Inner mitochondrial vesicles
Polymer nanodiscs
SMA
Transmission electron microscopy

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10.1016/j.bbamem.2021.183725

1-s2.0-S0005273621001735-mainFinal published version, 3.28 MBLicence: Taverne

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Janson, K., Zierath, J., Kyrilis, F. L., Semchonok, D. A., Hamdi, F., Skalidis, I., Kopf, A. H., Das, M., Kolar, C., Rasche, M., Vargas, C., Keller, S., Kastritis, P. L., & Meister, A. (2021). Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge. Biochimica et Biophysica Acta - Biomembranes, 1863(12), 1-10. Article 183725. https://doi.org/10.1016/j.bbamem.2021.183725

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title = "Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge",

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.",

keywords = "DIBMA, Inner mitochondrial vesicles, Polymer nanodiscs, SMA, Transmission electron microscopy",

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

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: {\textcopyright} 2021",

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doi = "10.1016/j.bbamem.2021.183725",

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Janson, K, Zierath, J, Kyrilis, FL, Semchonok, DA, Hamdi, F, Skalidis, I, Kopf, AH, Das, M, Kolar, C, Rasche, M, Vargas, C, Keller, S, Kastritis, PL & Meister, A 2021, 'Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge', Biochimica et Biophysica Acta - Biomembranes, vol. 1863, no. 12, 183725, pp. 1-10. https://doi.org/10.1016/j.bbamem.2021.183725

TY - JOUR

T1 - Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge

AU - Janson, Kevin

AU - Zierath, Jennifer

AU - Kyrilis, Fotis L.

AU - Semchonok, Dmitry A.

AU - Hamdi, Farzad

AU - Skalidis, Ioannis

AU - Kopf, Adrian H.

AU - Das, Manabendra

AU - Kolar, Cenek

AU - Rasche, Marie

AU - Vargas, Carolyn

AU - Keller, Sandro

AU - Kastritis, Panagiotis L.

AU - Meister, Annette

N1 - 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

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

KW - DIBMA

KW - Inner mitochondrial vesicles

KW - Polymer nanodiscs

KW - SMA

KW - Transmission electron microscopy

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U2 - 10.1016/j.bbamem.2021.183725

DO - 10.1016/j.bbamem.2021.183725

M3 - Article

C2 - 34384757

AN - SCOPUS:85112369846

SN - 0005-2736

VL - 1863

SP - 1

EP - 10

JO - Biochimica et Biophysica Acta - Biomembranes

JF - Biochimica et Biophysica Acta - Biomembranes

IS - 12

M1 - 183725

ER -

Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge

Abstract

Bibliographical note

Funding

Keywords

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