Biology:Nanodisc

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Short description: Synthetic model membrane system
Schematic illustration of a nanodisc with a 7-transmembrane protein embedded.
Schematic illustration of a MSP nanodisc with a 7-transmembrane protein embedded. Diameter is about 10 nm. Picture from Sligar Lab

A nanodisc is a synthetic model membrane system which assists in the study of membrane proteins.[1] Nanodiscs are discoidal proteins in which a lipid bilayer is surrounded by molecules that are amphipathic molecules including proteins, peptides, and synthetic polymers.[2] It is composed of a lipid bilayer of phospholipids with the hydrophobic edge screened by two amphipathic proteins. These proteins are called membrane scaffolding proteins (MSP) and align in double belt formation.[3][4][5] Nanodiscs are structurally very similar to discoidal high-density lipoproteins (HDL) and the MSPs are modified versions of apolipoprotein A1 (apoA1), the main constituent in HDL. Nanodiscs are useful in the study of membrane proteins because they can solubilise and stabilise membrane proteins[6] and represent a more native environment than liposomes, detergent micelles, bicelles and amphipols.

The art of making nanodiscs has progressed past using only the MSPs and lipids to make particles, leading to alternative strategies like peptide nanodiscs that use simpler proteins and synthetic nanodiscs that do not need any proteins for stabilization.

MSP nanodisc

The original nanodisc was produced by apoA1-derived MSPs from 2002.[3] The size and stability of these discs depend on the size of these proteins, which can be adjusted by truncation and fusion. In general, MSP1 proteins consist of one repeat, and MSP2s are double-sized.[7][8]

Peptide nanodisc

In peptide nanodiscs, the lipid bilayer is screened by amphipathic peptides instead of two MSPs. Peptide nanodiscs are structurally similar to MSP nanodiscs and the peptides also align in a double belt. They can stabilise membrane proteins,[9] but have higher polydispersity and are structurally less stable than MSP nanodiscs. Recent studies, however, showed that dimerization[10] and polymerization[11] of the peptides make them more stable.

Synthetic/Native nanodisc

Another way to mimic the native lipid membrane are synthetic polymers. Styrene-maleic acid co-polymers (SMAs)[12][13] called SMALPs or Lipodisq and Diisobutylene-maleic acid (DIBMA)[14] are such synthetic polymers (DIBMALPs). They can solubilize membrane proteins directly from cells or raw extract. They also have been used to study the lipid composition of several organisms.[15][16][17] It was discovered that all synthetic polymers which contained a styrene and maleic acid group can solubilize proteins.[18] These SMA nanoparticles have also been tested as possible drug delivery vehicle[19] and for the study of folding, post-translational modifications and lipid interactions of membrane proteins by native mass spectrometry.[20]

References

  1. ↑ "Dissecting the Structure of Membrane Proteins". Genetic Engineering & Biotechnology News 35 (17): 16–18, 21. 1 October 2015. doi:10.1089/gen.35.07.09. http://www.genengnews.com/gen-articles/dissecting-the-structure-of-membrane-proteins/5583/. "Nanodiscs are self-assembling nanoscale phospholipid bilayers that are stabilized using engineered membrane scaffold proteins.". 
  2. ↑ Anada, Chiharu; Ikeda, Keisuke; Egawa, Ayako; Fujiwara, Toshimichi; Nakao, Hiroyuki; Nakano, Minoru (April 2021). "Temperature- and composition-dependent conformational transitions of amphipathic peptide–phospholipid nanodiscs". Journal of Colloid and Interface Science 588: 522–530. doi:10.1016/j.jcis.2020.12.090. ISSN 0021-9797. PMID 33429348. http://dx.doi.org/10.1016/j.jcis.2020.12.090. 
  3. ↑ 3.0 3.1 "Self-Assembly of Discoidal Phospholipid Bilayer Nanoparticles with Membrane Scaffold Proteins". Nano Letters 2 (8): 853–856. 2002. doi:10.1021/nl025623k. Bibcode: 2002NanoL...2..853B. 
  4. ↑ "Membrane protein assembly into Nanodiscs". FEBS Letters 584 (9): 1721–7. May 2010. doi:10.1016/j.febslet.2009.10.024. PMID 19836392. 
  5. ↑ "Elliptical structure of phospholipid bilayer nanodiscs encapsulated by scaffold proteins: casting the roles of the lipids and the protein". Journal of the American Chemical Society 132 (39): 13713–22. October 2010. doi:10.1021/ja1030613. PMID 20828154. 
  6. ↑ "Cytochromes P450 in nanodiscs". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1814 (1): 223–9. January 2011. doi:10.1016/j.bbapap.2010.05.017. PMID 20685623. 
  7. ↑ "Directed self-assembly of monodisperse phospholipid bilayer Nanodiscs with controlled size". Journal of the American Chemical Society 126 (11): 3477–87. March 2004. doi:10.1021/ja0393574. PMID 15025475. 
  8. ↑ "Engineering extended membrane scaffold proteins for self-assembly of soluble nanoscale lipid bilayers". Protein Engineering, Design & Selection 23 (11): 843–8. November 2010. doi:10.1093/protein/gzq060. PMID 20817758. 
  9. ↑ "Self-assembling peptides form nanodiscs that stabilize membrane proteins". Soft Matter 10 (5): 738–52. February 2014. doi:10.1039/c3sm51727f. PMID 24651399. 
  10. ↑ "Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins". Soft Matter 12 (27): 5937–49. July 2016. doi:10.1039/c6sm00495d. PMID 27306692. Bibcode: 2016SMat...12.5937L. 
  11. ↑ "Formation of size-controlled, denaturation-resistant lipid nanodiscs by an amphiphilic self-polymerizing peptide". Colloids and Surfaces. B, Biointerfaces 146: 423–30. October 2016. doi:10.1016/j.colsurfb.2016.06.040. PMID 27393815. 
  12. ↑ "From polymer chemistry to structural biology: The development of SMA and related amphipathic polymers for membrane protein extraction and solubilisation". Chemistry and Physics of Lipids 221: 167–175. July 2019. doi:10.1016/j.chemphyslip.2019.03.008. PMID 30940445. https://ora.ox.ac.uk/objects/uuid:a9db376a-8e9f-46df-8c09-aa613265351e. 
  13. ↑ "Membrane proteins solubilized intact in lipid containing nanoparticles bounded by styrene maleic acid copolymer". Journal of the American Chemical Society 131 (22): 7484–5. June 2009. doi:10.1021/ja810046q. PMID 19449872. 
  14. ↑ "Formation of Lipid-Bilayer Nanodiscs by Diisobutylene/Maleic Acid (DIBMA) Copolymer". Langmuir 33 (50): 14378–14388. December 2017. doi:10.1021/acs.langmuir.7b03742. PMID 29160078. 
  15. ↑ "Lipid nanoparticle technologies for the study of G protein-coupled receptors in lipid environments". Biophysical Reviews 12 (6): 1287–1302. November 2020. doi:10.1007/s12551-020-00775-5. PMID 33215301. 
  16. ↑ "Lipidomic and in-gel analysis of maleic acid co-polymer nanodiscs reveals differences in composition of solubilized membranes". Communications Biology 4 (1): 218. February 2021. doi:10.1038/s42003-021-01711-3. PMID 33594255. 
  17. ↑ "Lipodisqs for eukaryote lipidomics with retention of viability: Sensitivity and resistance to Leucobacter infection linked to C.elegans cuticle composition". Chemistry and Physics of Lipids 222: 51–58. August 2019. doi:10.1016/j.chemphyslip.2019.02.005. PMID 31102583. https://ora.ox.ac.uk/objects/uuid:4d3c3aa1-3f12-443c-8ef0-c3647759832c/download_file?safe_filename=JuarezetalAAM2019.pdf&file_format=application%2Fpdf&type_of_work=Journal+article. 
  18. ↑ "Diisobutylene-maleic acid (DIBMA)" (in en-GB). https://cube-biotech.com/products/nanodisc-products/synthetic-polymers/diisobutylene-maleic-acid-dibma/. 
  19. ↑ "Physicochemical Characterization, Toxicity and In Vivo Biodistribution Studies of a Discoidal, Lipid-Based Drug Delivery Vehicle: Lipodisq Nanoparticles Containing Doxorubicin". Journal of Biomedical Nanotechnology 16 (4): 419–431. April 2020. doi:10.1166/jbn.2020.2911. PMID 32970975. http://urn.nb.no/URN:NBN:no-87934. 
  20. ↑ "Detergent-free Lipodisq Nanoparticles Facilitate High-Resolution Mass Spectrometry of Folded Integral Membrane Proteins". Nano Letters 21 (7): 2824–2831. March 2021. doi:10.1021/acs.nanolett.0c04911. PMID 33787280. 

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