Bioinspired, Size‐Tunable Self‐Assembly of Polymer–Lipid Bilayer Nanodiscs

Ravula, Thirupathi; Ramadugu, Sudheer Kumar; Mauro, Giacomo Di; Ramamoorthy, Ayyalusamy

doi:10.1002/ange.201705569

Cited by 50 publications

(75 citation statements)

References 38 publications

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“…Following the initial incorporation of PagP and bacteriorhodopsin into SMA nanodiscs (11), a variety of membrane proteins have been studied using similar preparations (12,15,16). Further development has led to similar polymers with greater pH stability and decreased susceptibility to divalent metal cations, among other favorable properties (17)(18)(19)(20)(21)(22).…”

mentioning

confidence: 99%

Macrodiscs Comprising SMALPs for Oriented Sample Solid-State NMR Spectroscopy of Membrane Proteins

Radoicic

Park

Opella

2018

Biophysical Journal

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Macrodiscs, which are magnetically alignable lipid bilayer discs with diameters of >30 nm, were obtained by solubilizing protein-containing liposomes with styrene-maleic acid copolymers. Macrodiscs provide a detergent-free phospholipid bilayer environment for biophysical and functional studies of membrane proteins under physiological conditions. The narrow resonance linewidths observed from membrane proteins in styrene-maleic acid macrodiscs advance structure determination by oriented sample solid-state NMR spectroscopy.

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confidence: 99%

Macrodiscs Comprising SMALPs for Oriented Sample Solid-State NMR Spectroscopy of Membrane Proteins

Radoicic

Park

Opella

2018

Biophysical Journal

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“…These results suggest that macro-nanodiscs possess a negative magnetic susceptibility and align in such a way that the lipid bilayer normal orients perpendicular to the magnetic field direction as shown in previous studies. 40,43,47 The magnetic susceptibility of these nanodiscs can be changed by the addition of paramagnetic metal ions such as YbCl3 which has a positive magnetic susceptibility. [48][49] To study the alignment behavior of macro-nanodiscs 31 P NMR spectra were acquired as a function of time by adding different concentrations of YbCl3 to the aligned macro-nanodiscs.…”

Section: Resultsmentioning

confidence: 99%

Magnetic-Alignment of Polymer Nanodiscs Probed by Solid-State NMR Spectroscopy

Ravula

Kim

Lee

et al. 2019

Preprint

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The ability of amphipathic polymers to self-assemble with lipids and form nanodiscs has been a boon for the field of functional reconstitution of membrane proteins. In a field dominated by detergent micelles, a unique feature of polymer nanodiscs is their much-desired ability to align in the presence of an external magnetic field. Magnetic alignment facilitates the application of solidstate NMR spectroscopy and aids in the measurement of residual dipolar couplings (RDCs) via well-established solution NMR spectroscopy. In this study, we comprehensively investigate the magnetic-alignment properties of SMA-QA polymer based nanodiscs by using 31 P and 14 N solidstate NMR experiments under static conditions. The results reported herein demonstrate the spontaneous magnetic-alignment of large-size (≥ 20 nm diameter) SMA-QA nanodiscs (also called as macro-nanodiscs) with the lipid-bilayer-normal perpendicular to the magnetic field direction. Consequently, the orientation of macro-nanodiscs are further shown to flip their alignment axis parallel to the magnetic field direction upon the addition of a paramagnetic lanthanide salt. These results demonstrate the use of SMA-QA polymer nanodiscs for solid-state NMR applications including structural studies on membrane proteins. 14 N NMR Experiments: Nitrogen-14 NMR spectra were acquired using a Bruker 400 MHz solidstate NMR spectrometer and a 5 mm double-resonance probe operating at the 14 N resonance frequency of 28.910 MHz. 14 N NMR spectra were recorded using the quadrupole-echo pulse sequence 46 with a 90° pulse length of 8 µs and an echo-delay of 80 µs. 14 N magnetization was acquired using 25 ms acquisition time, 20,000 scans and a recycle delay of 0.9 s with no 1 H decoupling.

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“…The martini DLPC lipid was chosen for our study as it provide a general phosphatidylcholine lipid and correspond to atomistic C12:0 dilauroyl (DLPC)-C14:0 dimyristoyl (DMPC) tails. In our previous experimental study, 1,2 we demonstrated the spontaneous lipid-nanodisc formation by both polymers selectively for phosphatidylcholine lipid with C14 tails. The DLPC lipid-bilayer was built using Martini insane python program and simulated for 2 µs prior to SMA-EA.…”

Section: Simulationmentioning

confidence: 90%

Self-Assembly of Polymer-Encased Lipid Nanodiscs and Membrane Protein Reconstitution

Sahoo¹,

Genjo²,

Moharana

et al. 2019

J. Phys. Chem. B

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The absence of detergent and curvature makes nanodiscs excellent membrane mimetics. The lack of structural and mechanistic model of polymer-encapsulated lipid nanodiscs limits their use in the study of the structure, dynamics, and functions of membrane proteins. In this study, we parameterized and optimized the coarse-graining (CG) bead mapping for two differently charged and functionalized copolymers, containing styrene–maleic acid (SMAEA) and polymethacrylate (PMAQA), for the Martini force-field framework and showed nanodisc formation (<8 nm diameter) on a time scale of tens of microseconds using molecular dynamics (MD) simulations. Structural models of ∼2.0 or 4.8 kDa PMAQA and ∼2.2 kDa SMAEA polymer-based lipid nanodiscs highlight the importance of the polymer chemical structure, size, and polymer–lipid ratio in the optimization of the nanodisc structure. The ideal spatial arrangement of polymers in nanodiscs, nanodisc size, and thermal stability obtained from our MD simulation correlates well with the experimental observations. The polymer–nanodiscs were tested for the reconstitution of single-pass or multipass transmembrane proteins. We expect this study to be useful in the development of novel polymer-based lipid nanodiscs and for the structural studies of membrane proteins.

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Bioinspired, Size‐Tunable Self‐Assembly of Polymer–Lipid Bilayer Nanodiscs

Cited by 50 publications

References 38 publications

Macrodiscs Comprising SMALPs for Oriented Sample Solid-State NMR Spectroscopy of Membrane Proteins

Macrodiscs Comprising SMALPs for Oriented Sample Solid-State NMR Spectroscopy of Membrane Proteins

Magnetic-Alignment of Polymer Nanodiscs Probed by Solid-State NMR Spectroscopy

Self-Assembly of Polymer-Encased Lipid Nanodiscs and Membrane Protein Reconstitution

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