skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structure of Diisobutylene Maleic Acid Copolymer (DIBMA) and Its Lipid Particle as a “Stealth” Membrane-Mimetic for Membrane Protein Research

You are accessing a document from the Department of Energy's (DOE) OSTI.GOV. This site is a product of DOE's Office of Scientific and Technical Information (OSTI) and is provided as a public service.

Visit OSTI to utilize additional information resources in energy science and technology.

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 » 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.« less

Authors:
Guo, Rong [1]; Sumner, Jacob [2]; Qian, Shuo  [2]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Grinnell College, IA (United States)
  2. 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}
}

Works referenced in this record:

The styrene–maleic acid copolymer: a versatile tool in membrane research
journal, December 2015


A comparison of SMA (styrene maleic acid) and DIBMA (di-isobutylene maleic acid) for membrane protein purification
journal, July 2020


Interpretation of solution scattering data from lipid nanodiscs
journal, February 2018


Insight into Clustering in Poly(ethylene oxide) Solutions
journal, September 2004


Ab initio electron density determination directly from solution scattering data
journal, January 2018


Effect of Polymer Composition and pH on Membrane Solubilization by Styrene-Maleic Acid Copolymers
journal, November 2016


SANS from Poly(ethylene oxide)/Water Systems
journal, October 2002


Structural studies of complex systems using small-angle scattering: a unified Guinier/power-law approach
journal, September 1994


Lipid dynamics in nanoparticles formed by maleic acid-containing copolymers: EPR spectroscopy and molecular dynamics simulations
journal, May 2020


Effects of charged lipids on the physicochemical and biological properties of lipid–styrene maleic acid copolymer discoidal particles
journal, May 2020


PSI-SMALP, a Detergent-free Cyanobacterial Photosystem I, Reveals Faster Femtosecond Photochemistry
journal, January 2020


Homogeneous nanodiscs of native membranes formed by stilbene–maleic-acid copolymers
journal, January 2020


Understanding the Structure and Dynamics of Complex Biomembrane Interactions by Neutron Scattering Techniques
journal, December 2020


Solubilization of Membrane Proteins into Functional Lipid-Bilayer Nanodiscs Using a Diisobutylene/Maleic Acid Copolymer
journal, January 2017


Stealth carriers for low-resolution structure determination of membrane proteins in solution
journal, January 2014


Interrogating Membrane Protein Conformational Dynamics within Native Lipid Compositions
journal, November 2017


Formation of Lipid-Bilayer Nanodiscs by Diisobutylene/Maleic Acid (DIBMA) Copolymer
journal, December 2017


Influence of lipid bilayer properties on nanodisc formation mediated by styrene/maleic acid copolymers
journal, January 2016


Peptide-Induced Asymmetric Distribution of Charged Lipids in a Vesicle Bilayer Revealed by Small-Angle Neutron Scattering
journal, August 2011


Stable and Functional Rhomboid Proteases in Lipid Nanodiscs by Using Diisobutylene/Maleic Acid Copolymers
journal, October 2018


The suite of small-angle neutron scattering instruments at Oak Ridge National Laboratory
journal, February 2018


Synthesis, Characterization and Applications of a Perdeuterated Amphipol
journal, October 2014


Influence of Mg2+ and Ca2+ on nanodisc formation by diisobutylene/maleic acid (DIBMA) copolymer
journal, July 2019


ATSAS 2.8 : a comprehensive data analysis suite for small-angle scattering from macromolecular solutions
journal, June 2017


Tissue-based map of the human proteome
journal, January 2015


Detergent-free purification of ABC (ATP-binding-cassette) transporters
journal, June 2014


BioXTAS RAW : improvements to a free open-source program for small-angle X-ray scattering data reduction and analysis
journal, September 2017


Small-angle scattering by fractal systems
journal, December 1988


The Magic of Bicelles Lights Up Membrane Protein Structure
journal, August 2012


An Algorithm for Least-Squares Estimation of Nonlinear Parameters
journal, June 1963


Nanodiscs for structural and functional studies of membrane proteins
journal, June 2016


Designing Mixed Detergent Micelles for Uniform Neutron Contrast
journal, October 2017


Bicelles Rich in both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins
journal, June 2020


Small-angle neutron scattering and contrast variation: a powerful combination for studying biological structures
journal, October 2010


Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation
journal, November 2018


Covalently circularized nanodiscs for studying membrane proteins and viral entry
journal, November 2016


Solubilization and Stabilization of Membrane Proteins by Cycloalkane-Modified Amphiphilic Polymers
journal, June 2020


Complexity of seemingly simple lipid nanodiscs
journal, November 2020


Responsive hydrophobically associating polymers: a review of structure and properties
journal, December 2001


Influence of DIBMA Polymer Length on Lipid Nanodisc Formation and Membrane Protein Extraction
journal, December 2020


NMR Perspectives of the KcsA Potassium Channel in the Membrane Environment
journal, August 2019


Detergent-Free Formation and Physicochemical Characterization of Nanosized Lipid-Polymer Complexes: Lipodisq
journal, March 2012


How many drug targets are there?
journal, December 2006


Detergent-free extraction of a functional low-expressing GPCR from a human cell line
journal, March 2020


Membrane Proteins Solubilized Intact in Lipid Containing Nanoparticles Bounded by Styrene Maleic Acid Copolymer
journal, June 2009


Molecular structures of fluid phase phosphatidylglycerol bilayers as determined by small angle neutron and X-ray scattering
journal, September 2012


An acid-compatible co-polymer for the solubilization of membranes and proteins into lipid bilayer-containing nanoparticles
journal, January 2018


DIBMA nanodiscs keep α-synuclein folded
journal, September 2020


diisobutylene structure