Structure of Diisobutylene Maleic Acid Copolymer (DIBMA) and Its Lipid Particle as a “Stealth” Membrane-Mimetic for Membrane Protein Research
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Abstract
The study of membrane proteins remains challenging, especially in a native membrane environment. Recently, major progress has been made using maleic acid copolymers, such as styrene maleic acid, to purify membrane proteins and study them directly with native lipids associated with the membrane. Additional maleic acid copolymers, such as diisobutylene maleic acid (DIBMA) membrane-mimetic systems, are being developed and found to have improved spectroscopic properties and pH stability. We studied DIBMA and its lipid particles in solution to better understand its assembly, without and with the lipids, to provide an insight regarding how to use it in solution for better membrane extraction. Using small-angle neutron and X-ray scattering (SANS/SAXS), we show that DIBMA organizes into structures of different size scales at various concentrations and ionic strengths. The polymer performed reasonably well under most solvent conditions except in very low concentrations and high-salt conditions that could result in limited interaction with lipids. To explore DIBMA lipid particles as a suitable membrane-mimetic system for neutron scattering studies of membrane proteins, we measured and determined the contrast-matching point of DIBMA to be ~12% (v/v) D2O — similar to that of most protiated lipid molecules but distinct from that of regular protiated proteins —more »« less
- Authors:
-
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Grinnell College, IA (United States)
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1807315
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- ACS Applied Bio Materials
- Additional Journal Information:
- Journal Volume: 4; Journal Issue: 6; Journal ID: ISSN 2576-6422
- Publisher:
- ACS Publications
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; DIBMA; membrane-mimetic; lipid nanodisc; lipid particle; SANS; neutron scattering; small-angle scattering; membrane protein; Lipids; peptides and proteins; nanoparticles; membranes; polymers
Citation Formats
Guo, Rong, Sumner, Jacob, and Qian, Shuo. Structure of Diisobutylene Maleic Acid Copolymer (DIBMA) and Its Lipid Particle as a “Stealth” Membrane-Mimetic for Membrane Protein Research. United States: N. p., 2021.
Web. doi:10.1021/acsabm.0c01626.
Guo, Rong, Sumner, Jacob, & Qian, Shuo. Structure of Diisobutylene Maleic Acid Copolymer (DIBMA) and Its Lipid Particle as a “Stealth” Membrane-Mimetic for Membrane Protein Research. United States. https://doi.org/10.1021/acsabm.0c01626
Guo, Rong, Sumner, Jacob, and Qian, Shuo. 2021.
"Structure of Diisobutylene Maleic Acid Copolymer (DIBMA) and Its Lipid Particle as a “Stealth” Membrane-Mimetic for Membrane Protein Research". United States. https://doi.org/10.1021/acsabm.0c01626. https://www.osti.gov/servlets/purl/1807315.
@article{osti_1807315,
title = {Structure of Diisobutylene Maleic Acid Copolymer (DIBMA) and Its Lipid Particle as a “Stealth” Membrane-Mimetic for Membrane Protein Research},
author = {Guo, Rong and Sumner, Jacob and Qian, Shuo},
abstractNote = {The study of membrane proteins remains challenging, especially in a native membrane environment. Recently, major progress has been made using maleic acid copolymers, such as styrene maleic acid, to purify membrane proteins and study them directly with native lipids associated with the membrane. Additional maleic acid copolymers, such as diisobutylene maleic acid (DIBMA) membrane-mimetic systems, are being developed and found to have improved spectroscopic properties and pH stability. We studied DIBMA and its lipid particles in solution to better understand its assembly, without and with the lipids, to provide an insight regarding how to use it in solution for better membrane extraction. Using small-angle neutron and X-ray scattering (SANS/SAXS), we show that DIBMA organizes into structures of different size scales at various concentrations and ionic strengths. The polymer performed reasonably well under most solvent conditions except in very low concentrations and high-salt conditions that could result in limited interaction with lipids. To explore DIBMA lipid particles as a suitable membrane-mimetic system for neutron scattering studies of membrane proteins, we measured and determined the contrast-matching point of DIBMA to be ~12% (v/v) D2O — similar to that of most protiated lipid molecules but distinct from that of regular protiated proteins — providing a natural contrast for separating their neutron scattering signals. Using SANS contrast variation, we demonstrated that the scattering from the whole lipid particle can be annihilated. Further, we determined that a well-defined lipid nanodisc structure with DIBMA was contrast-matched. These results demonstrate that the DIBMA lipid particle is an outstanding “stealth” membrane-mimetic for membrane proteins. The results provide a structural framework for understanding the organization and assembly process of the polymer itself and the lipid molecules. Such an understanding is imperative for structural techniques such as cryo-electron microscopy, nuclear magnetic resonance, small-angle scattering, and other biophysical techniques.},
doi = {10.1021/acsabm.0c01626},
url = {https://www.osti.gov/biblio/1807315},
journal = {ACS Applied Bio Materials},
issn = {2576-6422},
number = 6,
volume = 4,
place = {United States},
year = {Tue Apr 06 00:00:00 EDT 2021},
month = {Tue Apr 06 00:00:00 EDT 2021}
}
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