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

Hall, Stephen B.; Tognoloni, Cecilia; Charlton, Jack; Bragginton, Eilis C.; Rothnie, Alice; Sridhar, Pooja; Wheatley, Mark; Knowles, Timothy J.; Arnold, Thomas; Edler, Karen J.; Dafforn, Timothy R.

doi:10.1039/c8nr01322e

Cited by 100 publications

(120 citation statements)

References 58 publications

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“…Despite the great potential, polymer nanodisks have suffered from some major drawbacks due to the intrinsic chemical properties of SMA inherent to its hydrophobic and hydrophilic units . Several studies have already shown an enhancement of SMA's stability by the modification of hydrophilic functional units . The most common hydrophobic group used in SMA polymer nanodisks is the styrene moiety.…”

Section: Properties Of Alkyl‐paa‐dmpc‐nanodisksmentioning

confidence: 99%

Hydrophobic Functionalization of Polyacrylic Acid as a Versatile Platform for the Development of Polymer Lipid Nanodisks

Hardin

Ravula

Mauro

et al. 2019

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Polymer nanodisks have shown great potential as membrane mimetics that enable the study of functional membrane protein structural biology and also have a wider application in other fields such as drug delivery. To achieve these research goals, the ability to have a cheap, simple, fully customizable platform for future nanodisks technology applications is paramount. Here, a facile functionalization of polyacrylic acid (PAA) with varying hydrophobic groups that form nanodisks at different sizes is successfully demonstrated. The study shows that the choice of hydrophobic group can have a noticeable effect on the polymer solubilization properties and polymer‐induced perturbation to the encased lipid bilayer. Due to this robust, tunable chemical synthesis method, PAA is an exciting platform for the future optimization of the hydrophobic, hydrophilic, or direct purposed functionalizations for polymer nanodisks.

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Section: Properties Of Alkyl‐paa‐dmpc‐nanodisksmentioning

confidence: 99%

Hydrophobic Functionalization of Polyacrylic Acid as a Versatile Platform for the Development of Polymer Lipid Nanodisks

Hardin

Ravula

Mauro

et al. 2019

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“…Polymers such as styrene maleimide copolymer-lipid nanoparticles (SMILPs) and styrene-maleic acid copolymer-lipid nanoparticles (SMALPs) can solubilize the protein of interest without the use of detergent. SMALPs and SMILPs form nearly homogenous nanoparticles and provide a native mimicking environment with lipids that are compatible with the protein of interest, while stabilizing the protein with minimal interference 15,28 .…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have used polymers to form membrane mimetic systems 14,15,28 and commercial polymers have been used to characterize the formation of lipodisq nanoparticles using dynamic light scattering (DLS), 31 P Solid State Nuclear Magnetic Resonance (SSNMR), and Transmission Electron Microscopy (TEM) 29 . Recently, our lab has shown that 3:1 styrene-maleic acid can be synthesized in a laboratory setting using reversible addition-fragmentation chain transfer polymerization (RAFT) polymerization and successfully used to characterize the structure of styrene-maleic acid copolymerlipid nanoparticles (SMALPs) 15,30 .…”

Section: Introductionmentioning

confidence: 99%

Characterizing the structure of styrene-maleic acid copolymer-lipid nanoparticles (SMALPs) using RAFT polymerization for membrane protein spectroscopic studies

Harding

Dixit

Burridge

et al. 2019

Chemistry and Physics of Lipids

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Membrane proteins play an important role in maintaining the structure and physiology of an organism. Despite their significance, spectroscopic studies involving membrane proteins remain challenging due to the difficulties in mimicking their native lipid bilayer environment. Membrane mimetic systems such as detergent micelles, liposomes, bicelles, nanodiscs, lipodisqs have improved the solubility and folding properties of the membrane proteins for structural studies, however, each mimetic system suffers from its own limitations. In this study, using three different lipid environments, vesicles were titrated with styrene-maleic acid (StMA) copolymer leading to a homogeneous SMALP system (~10 nm) at a weight ratio of 1:1.5 (vesicle: StMA solution). A combination of Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) was used to characterize these SMALPs. We used a controlled synthesis mechanism to synthesize StMA based block copolymers called reversible addition-fragmentation chain transfer polymerization (RAFT) SMALPs. Incorporation of the Voltage sensor Domain of KCNQ1 (Q1-VSD) into RAFT SMALPs indicates that this is a promising application of this system to study membrane proteins using different biophysical techniques. V165C in Q1-VSD corresponding to the hydrophobic region was incorporated into the SMALP system. Continuous Wave-Electron Paramagnetic Resonance (CW-EPR) line shape analysis showed line shape broadening, exposing a lower rigid component and a faster component of the spin label.

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“…The introduction of amphiphilic polymers that form lipid nanodiscs has most notably contributed to the study of membrane proteins (MPs) and allows for their functional and structural study in a tunable native‐like membrane environment . While polymer nanodiscs are the youngest of the nanodisc field, they are showing great potential due to the simplicity of their synthesis, their diverse chemical tunability, and their ability to directly extract membrane proteins from their cellular environment at practical cost . Nanodiscs are a useful tool for NMR spectroscopy since their size can be tuned to conditions favorable to both solution and solid‐state NMR.…”

Section: Figurementioning

confidence: 99%

Metal‐Chelated Polymer Nanodiscs for NMR Studies

et al. 2019

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Paramagnetic relaxation enhancement (PRE) is commonly used to speed up spin lattice relaxation time (T1) for rapid data acquisition in NMR structural studies. Consequently, there is significant interest in novel paramagnetic labels for enhanced NMR studies on biomolecules. Herein, we report the synthesis and characterization of a modified poly(styrene‐co‐maleic acid) polymer which forms nanodiscs while showing the ability to chelate metal ions. Cu2+‐chelated nanodiscs are demonstrated to reduce the T1 of protons for both polymer and lipid‐nanodisc components. The chelated nanodiscs also decrease the proton T1 values for a water‐soluble DNA G‐quadruplex. These results suggest that polymer nanodiscs functionalized with paramagnetic tags can be used to speed‐up data acquisition from lipid bilayer samples and also to provide structural information from water‐soluble biomolecules.

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

Abstract: Positively charged poly(styrene-co-maleimide) extracts functional membrane proteins into nanodiscs, overcoming some limitations of current nanodisc technology.

Cited by 100 publications

References 58 publications

Hydrophobic Functionalization of Polyacrylic Acid as a Versatile Platform for the Development of Polymer Lipid Nanodisks

Hydrophobic Functionalization of Polyacrylic Acid as a Versatile Platform for the Development of Polymer Lipid Nanodisks

Characterizing the structure of styrene-maleic acid copolymer-lipid nanoparticles (SMALPs) using RAFT polymerization for membrane protein spectroscopic studies

Metal‐Chelated Polymer Nanodiscs for NMR Studies

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