Solubilization of lipids and lipid phases by the styrene–maleic acid copolymer

Pardo, Juan J. Domínguez; Dörr, Jonas M.; Iyer, Aditya; Cox, Ruud C.; Scheidelaar, Stefan; Koorengevel, Martijn C.; Subramaniam, Vinod; Killian, J. Antoinette

doi:10.1007/s00249-016-1181-7

Cited by 72 publications

(46 citation statements)

References 44 publications

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“…No correlation was observed between the size of the nano-disks and the M n of the polymer rim. These values are in line with the size values reported previously for similar self-assemblies (3,4,7,8). The only exception is the solubilized fraction obtained upon addition of the SMA 3:1 P96 fraction, which does not seem to contain nanodisks but micrometer-scaled particles.…”

Section: Sma-purified Fractions Yield Nanodisks Of Approximately the supporting

confidence: 91%

“…Size characterization of di-14:0 PC nanodisks was performed by transmission electron microscopy. Aliquots from the nanodisk solutions used for DLS analyses were diluted to a final 0.5 mM and adsorbed on carbon-coated mica following the carbon flotation technique, then stained with a staining solution containing 2% (w/v) sodium silicotungstate as detailed before (8). Images were taken under low-dose conditions at a nominal magnification of 49,000Â with a T12 electron microscope (FEI, Hillsboro, OR) at an operating voltage of 120 kV using an ORIUS SC1000 camera (Gatan, Pleasanton, CA).…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

“…Styrene-maleic acid (SMA) copolymers are in the spotlight of membrane protein research because of their ability to solubilize lipid membranes into nanodisks (for reviews, see (1,2)). SMA-mediated solubilization offers many advantages over conventional solubilization methods based on the use of detergents, including retention of the membrane architecture (i.e., lipid bilayer conformation) in nanodisks (3,4) and the suitability of nanodisk particles for analysis by biophysical techniques such as NMR (5,6), turbidimetry (7,8), and calorimetry (3,9,10).…”

Section: Introductionmentioning

confidence: 99%

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Membrane Solubilization by Styrene-Maleic Acid Copolymers: Delineating the Role of Polymer Length

Pardo

Koorengevel

Uwugiaren

et al. 2018

Biophysical Journal

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Styrene-maleic acid (SMA) copolymers have attracted interest in membrane research because they allow the solubilization and purification of membrane-spanning proteins from biological membranes in the form of native-like nanodisks. However, our understanding of the underlying SMA-lipid interactions is hampered by the fact that SMA preparations are very polydisperse. Here, we obtained fractions of the two most commonly used SMA preparations: SMA 2:1 and SMA 3:1 (both with specified M ∼10 kD), with different number-average molecular weight (M) and styrene content. The fractionation is based on the differential solubility of styrene-maleic anhydride (SMAnh) in hexane and acetone mixtures. SMAnh fractions were hydrolyzed to SMA and added to lipid self-assemblies. It was found that SMA fractions inserted in monolayers and solubilized vesicles to a different extent, with the highest efficiency being observed for low-M SMA polymers. Electron microscopy and dynamic light scattering size analyses confirmed the presence of nanodisks independent of the M of the SMA polymers forming the belt, and it was shown that the nanodisks all have approximately the same size. However, nanodisks bounded by high-M SMA polymers were more stable than those bounded by low-M polymers, as indicated by a better retention of the native lipid thermotropic properties and by slower exchange rates of lipids between nanodisks. In conclusion, we here present a simple method to separate SMAnh molecules based on their M from commercial SMAnh blends, which allowed us to obtain insights into the importance of SMA length for polymer-lipid interactions.

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Section: Sma-purified Fractions Yield Nanodisks Of Approximately the supporting

confidence: 91%

Section: Transmission Electron Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Membrane Solubilization by Styrene-Maleic Acid Copolymers: Delineating the Role of Polymer Length

Pardo

Koorengevel

Uwugiaren

et al. 2018

Biophysical Journal

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“…The present finding that SMALPs quickly exchange lipids then means that this enrichment must result from preferential protein/lipid interactions that are preserved in SMALPs, where they are sufficiently strong to retain these lipids in the immediate vicinity of the protein. In other words, the SMALPed “lipidome” is not merely a snapshot40 of the situation in the original membrane at the time of solubilisation but reflects rather strong protein/lipid interactions. Conversely, it seems plausible that weaker protein/lipid interactions, although present in the membrane before solubilisation, could be lost even after SMALP formation.…”

Section: Resultsmentioning

confidence: 99%

Fast Collisional Lipid Transfer Among Polymer-Bounded Nanodiscs

Arenas

Danielczak

Martel

et al. 2017

Sci Rep

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Some styrene/maleic acid (SMA) copolymers solubilise membrane lipids and proteins to form polymer-bounded nanodiscs termed SMA/lipid particles (SMALPs). Although SMALPs preserve a lipid-bilayer core, they appear to be more dynamic than other membrane mimics. We used time-resolved Förster resonance energy transfer and small-angle neutron scattering to determine the kinetics and the mechanisms of phospholipid transfer among SMALPs. In contrast with vesicles or protein-bounded nanodiscs, SMALPs exchange lipids not only by monomer diffusion but also by fast collisional transfer. Under typical experimental conditions, lipid exchange occurs within seconds in the case of SMALPs but takes minutes to days in the other bilayer particles. The diffusional and second-order collisional exchange rate constants for SMALPs at 30 °C are kdif = 0.287 s−1 and kcol = 222 M−1s−1, respectively. Together with the fast kinetics, the observed invariability of the rate constants with probe hydrophobicity and the moderate activation enthalpy of ~70 kJ mol−1 imply that lipids exchange through a “hydrocarbon continuum” enabled by the flexible nature of the SMA belt surrounding the lipid-bilayer core. Owing to their fast lipid-exchange kinetics, SMALPs represent highly dynamic equilibrium rather than kinetically trapped membrane mimics, which has important implications for studying protein/lipid interactions in polymer-bounded nanodiscs.

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“…Those formed from synthetic lipids may be smaller, with sizes of 6–10 nm reported using XIRAN 25010 polymer [24]. The discs comprise an inner patch of bilayer surrounded by a belt of polymer, as visualized by small angle neutron scattering using hydrogenated and deuterated lipids for contrast [11].…”

Section: Structures Of Membrane Assembliesmentioning

confidence: 99%

Membrane biology visualized in nanometer-sized discs formed by styrene maleic acid polymers

Esmaili¹,

Overduin²

2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Discovering how membrane proteins recognize signals and passage molecules remains challenging. Life depends on compartmentalizing these processes into dynamic lipid bilayers that are technically difficult to work with. Several polymers have proven adept at separating the responsible machines intact for detailed analysis of their structures and interactions. Styrene maleic acid (SMA) co-polymers efficiently solubilize membranes into native nanodiscs and, unlike amphipols and membrane scaffold proteins, require no potentially destabilizing detergents. Here we review progress with the SMA lipid particle (SMALP) system and its impacts including three dimensional structures and biochemical functions of peripheral and transmembrane proteins. Polymers systems are emerging to tackle the remaining challenges for wider use and future applications including in membrane proteomics, structural biology of transient or unstable states, and discovery of ligand and drug-like molecules specific for native lipid-bound states.

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Solubilization of lipids and lipid phases by the styrene–maleic acid copolymer

Cited by 72 publications

References 44 publications

Membrane Solubilization by Styrene-Maleic Acid Copolymers: Delineating the Role of Polymer Length

Membrane Solubilization by Styrene-Maleic Acid Copolymers: Delineating the Role of Polymer Length

Fast Collisional Lipid Transfer Among Polymer-Bounded Nanodiscs

Membrane biology visualized in nanometer-sized discs formed by styrene maleic acid polymers

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