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Biophys J. 2018 Aug 7;115(3):494-502. doi: 10.1016/j.bpj.2018.06.018. Epub 2018 Jun 20.

Molecular Mechanism of Lipid Nanodisk Formation by Styrene-Maleic Acid Copolymers.

Author information

1
State Key Laboratory of Mechanics and Control of Mechanical Structures, Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, Nanjing, People's Republic of China; Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Groningen, the Netherlands; Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands.
2
College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing, People's Republic of China.
3
Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Groningen, the Netherlands; Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands.
4
State Key Laboratory of Mechanics and Control of Mechanical Structures, Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, Nanjing, People's Republic of China.
5
Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Groningen, the Netherlands; Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands. Electronic address: s.j.marrink@rug.nl.

Abstract

Experimental characterization of membrane proteins often requires solubilization. A recent approach is to use styrene-maleic acid (SMA) copolymers to isolate membrane proteins in nanometer-sized membrane disks, or so-called SMA lipid particles (SMALPs). The approach has the advantage of allowing direct extraction of proteins, keeping their native lipid environment. Despite the growing popularity of using SMALPs, the molecular mechanism behind the process remains poorly understood. Here, we unravel the molecular details of the nanodisk formation by using coarse-grained molecular dynamics simulations. We show how SMA copolymers bind to the lipid bilayer interface, driven by the hydrophobic effect. Due to the concerted action of multiple adsorbed copolymers, large membrane defects appear, including small, water-filled pores. The copolymers can stabilize the rim of these pores, leading to pore growth and membrane disruption. Although complete solubilization is not seen on the timescale of our simulations, self-assembly experiments show that small nanodisks are the thermodynamically preferred end state. Our findings shed light on the mechanism of SMALP formation and on their molecular structure. This can be an important step toward the design of optimized extraction tools for membrane protein research.

PMID:
29980293
PMCID:
PMC6084417
[Available on 2019-08-07]
DOI:
10.1016/j.bpj.2018.06.018
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