Advertisement

The Journal of Membrane Biology

, Volume 247, Issue 9–10, pp 759–796 | Cite as

Amphipols for Each Season

  • Manuela Zoonens
  • Jean-Luc PopotEmail author
Article

Abstract

Amphipols (APols) are short amphipathic polymers that can substitute for detergents at the transmembrane surface of membrane proteins (MPs) and, thereby, keep them soluble in detergent free aqueous solutions. APol-trapped MPs are, as a rule, more stable biochemically than their detergent-solubilized counterparts. APols have proven useful to produce MPs, most noticeably by assisting their folding from the denatured state obtained after solubilizing MP inclusion bodies in either SDS or urea. They facilitate the handling in aqueous solution of fragile MPs for the purpose of proteomics, structural and functional studies, and therapeutics. Because APols can be chemically labeled or functionalized, and they form very stable complexes with MPs, they can also be used to functionalize those indirectly, which opens onto many novel applications. Following a brief recall of the properties of APols and MP/APol complexes, an update is provided of recent progress in these various fields.

Keywords

Membrane proteins Surfactants Stabilization Folding Biochemistry Biophysics 

Abbreviations

2D

Two-dimensional

3D

Three-dimensional

A8-35

A poly(sodium acrylate) based amphipol comprising ~35 % of free carboxylates, ~25 % of octyl chains, ~40 % of isopropyl groups, whose number average molar mass is ~4.3 kDa

A8-75

A poly(sodium acrylate) based amphipol comprising ~75 % of free carboxylates, ~25 % of octyl chains, whose number average molar mass is ~4 kDa

APol

Amphipol

AUC

Analytical ultracentrifugation

BAPol

Biotinylated A8-35

BLM

Black lipid membrane

BN-PAGE

Blue native polyacrylamide gel electrophoresis

BR

Bacteriorhodopsin

CAC

Critical aggregation concentration

CD

Circular dichroism

Đ

Polydispersity index

cmc

Critical micellar concentration

DAGK

Diacylglycerol kinase

DAPol

A8-35 with deuterated octylamine and isopropylamine side chains

DHPC

Dihexanoylphosphatidylcholine

DLS

Dynamic light scattering

DPC

Dodecylphosphocholine

DPn

See 〈Xn

EM

Electron microscopy

EPR

Electron paramagnetic resonance

ESI

Electron spray ionization

FAPol

Fluorescently-labeled A8-35

FAPolAF647

Alexa Fluor 647-labeled A8-35

FAPolNBD

Nitrobenzoxadiazole-labeled A8-35

FAPolrhod

Rhodamine-labeled A8-35

FRET

Förster resonance energy transfer

GFP

Green fluorescent protein

GPCR

G protein-coupled receptor

HAPol

Hydrogenated A8-35

His6PEG

N-(Penta(histidyl)histidinamide)-8-amino-3,6-dioxa-octanamide

His-tag

Hexahistidine tag

HistAPol

Hexahistidine tag-carrying A8-35

IMAC

Immobilized metal ion affinity chromatography

ImidAPol

Imidazole-carrying A8-35

IMS

Ion mobility spectrometry

INS

Inelastic neutron scattering

ITC

Isothermal titration calorimetry

KpOmpA

The transmembrane domain of outer membrane protein A from Klebsiella pneumoniae

LTB4

Leukotriene B4

Mn〉 (also written \( \bar{M}_{\text{n}} \))

Number-average molar mass

MALDI

Matrix-assisted laser desorption ionization

MOMP

The major outer membrane protein from Chlamydia trachomatis

MP

Membrane protein

MS

Mass spectrometry

MW

Molecular weight

nAChR

Nicotinic acetylcholine receptor

NAPol

Non-ionic APol

NBD

7-Nitrobenz-2-oxa-1,3-diazol-4-yle

ND

Nanodisc

NOE

Nuclear Overhauser effect

NTA

Nitrilotriacetic acid

ODN

Oligodeoxynucleotide

OligAPol

ODN-carrying A8-35

OmpA, OmpF, OmpX

Respectively outer membrane proteins A, F and X from Escherichia coli

PAA

Poly(acrylic acid)

PAGE

Polyacrylamide gel electrophoresis

PC-APol

Phosphorylcholine-based APol

perDAPol

Perdeuterated A8-35

QENS

Quasi-elastic neutron scattering

SANS

Small angle neutron scattering

SAPol

Sulfonated amphipol derived from A8-75, comprising ~40 % of taurine moieties

SAXS

Small angle X-ray scattering

SDS

Sodium dodecyl sulfate

SERCA1a

The sarcoplasmic calcium ATPase from twitch muscle

SERS

Surface-enhanced Raman scattering

SMFS

Single-molecule force spectrometry

SPR

Surface plasmon resonance

SR

Synchrotron radiation

STEM

Scanning transmission EM

Structure II

Secondary structure

SulfidAPol

Sulfide-carrying APol

TOF

Time of flight

tOmpA

The transmembrane domain of OmpA from E. coli

TRP

Transient receptor potential

UAPol

Universal amphipol

UAPol-NH2

Amine-carrying A8-35

Xn〉 (also written \( \bar{X}_{\text{n}} \), formerly DPn)

Number-average degree of polymerization

Notes

Acknowledgments

Particular thanks are due to our colleagues from UMR 7099 and from other laboratories for reading the manuscript, for suggestions, for communication of unpublished data, and for permission to reproduce figures taken from their articles. Work performed in our laboratory has been funded principally by the French Centre National de la Recherche Scientifique, University Paris-7 Denis Diderot, the Human Frontier Scientific Program Organization, the European Community, the Agence Nationale pour la Recherche and the US National Institutes of Health.

References

  1. Althoff T, Mills DJ, Popot J-L, Kühlbrandt W (2011) Assembly of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J 30:4652–4664CrossRefGoogle Scholar
  2. Arunmanee W, Harris JR, Lakey JH (2014) Outer membrane protein F stabilised with minimal amphipol forms linear arrays and LPS-dependent 2D crystals. J Membr Biol. doi: 10.1007/s00232-014-9640-5 CrossRefGoogle Scholar
  3. Banères J-L, Popot J-L, Mouillac B (2011) New advances in production and functional folding of G protein-coupled receptors. Trends Biotechnol 29:314–322CrossRefGoogle Scholar
  4. Banerjee S, Sen K, Pal TK, Guha SK (2012) Poly(styrene-co-maleic acid)-based pH-sensitive liposomes mediate cytosolic delivery of drugs for enhanced cancer chemotherapy. Int J Pharm 436:786–797PubMedGoogle Scholar
  5. Bano F, Fruk L, Sanavio B, Glettenberg M, Casalis L, Niemeyer CM, Scoles G (2009) Toward multiprotein nanoarrays using nanografting and DNA-directed immobilization of proteins. Nano Lett 9:2614–2618PubMedGoogle Scholar
  6. Basit H, Sharma S, Van der Heyden A, Gondran C, Breyton C, Dumy P, Winnik FM, Labbé P (2012) Amphipol mediated surface immobilization of FhuA: a platform for label-free detection of the bacteriophage protein pb5. Chem Commun 48:6037–6039Google Scholar
  7. Bazzacco P (2009) Non-ionic amphipols: new tools for in vitro studies of membrane proteins. Validation and development of biochemical and biophysical applications. Ph. D. Thesis, Université Paris-7, Paris, 176 pGoogle Scholar
  8. Bazzacco P, Sharma KS, Durand G, Giusti F, Ebel C, Popot J-L, Pucci B (2009) Trapping and stabilization of integral membrane proteins by hydrophobically grafted glucose-based telomers. Biomacromolecules 10:3317–3326PubMedGoogle Scholar
  9. Bazzacco P, Billon-Denis E, Sharma KS, Catoire LJ, Mary S, Le Bon C, Point E, Banères J-L, Durand G, Zito F, Pucci B, Popot J-L (2012) Non-ionic homopolymeric amphipols: application to membrane protein folding, cell-free synthesis, and solution NMR. Biochemistry 51:1416–1430PubMedGoogle Scholar
  10. Bechara C, Bolbach G, Bazzacco P, Sharma SK, Durand G, Popot J-L, Zito F, Sagan S (2012) MALDI mass spectrometry analysis of membrane protein/amphipol complexes. Anal Chem 84:6128–6135PubMedGoogle Scholar
  11. Bellot G, McClintock MA, Chou JJ, Shih WM (2013) DNA nanotubes for NMR structure determination of membrane proteins. Nat Protoc 8:755–770PubMedGoogle Scholar
  12. Breyton C, Pucci B, Popot J-L (2010) Amphipols and fluorinated surfactants: two alternatives to detergents for studying membrane proteins in vitro. In: Mus-Veteau I (ed) Heterologous expression of membrane proteins: methods and protocols. The Humana Press, Totowa, pp 219–245Google Scholar
  13. Buchanan SK, Yamashita S, Fleming KG (2012) Structure and folding of outer membrane proteins. In: Tamm LK (ed) Membranes. Academic Press, Elsevier, Oxford, pp 139–163Google Scholar
  14. Caffrey M (2011) Crystallizing membrane proteins for structure-function studies using lipidic mesophases. Biochem Soc Trans 39:725–732PubMedPubMedCentralGoogle Scholar
  15. Cao E, Liao M, Cheng Y, Julius D (2013) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504:113–118PubMedPubMedCentralGoogle Scholar
  16. Catoire LJ, Zoonens M, van Heijenoort C, Giusti F, Popot J-L, Guittet E (2009) Inter- and intramolecular contacts in a membrane protein/surfactant complex observed by heteronuclear dipole-to-dipole cross-relaxation. J Magn Res 197:91–95Google Scholar
  17. Catoire LJ, Damian M, Giusti F, Martin A, van Heijenoort C, Popot J-L, Guittet E, Banères J-L (2010a) Structure of a GPCR ligand in its receptor-bound state: leukotriene B4 adopts a highly constrained conformation when associated to human BLT2. J Am Chem Soc 132:9049–9057PubMedGoogle Scholar
  18. Catoire LJ, Zoonens M, van Heijenoort C, Giusti F, Guittet E, Popot J-L (2010b) Solution NMR mapping of water-accessible residues in the transmembrane β-barrel of OmpX. Eur Biophys J 39:623–630PubMedGoogle Scholar
  19. Catoire LJ, Damian M, Baaden M, Guittet E, Banères J-L (2011) Electrostatically-driven fast association and perdeuteration allow detection of transferred cross-relaxation for G protein-coupled receptor ligands with equilibrium dissociation constants in the high-to-low nanomolar range. J Biomol NMR 50:191–195PubMedGoogle Scholar
  20. Catoire LJ, Warnet XL, Warschawski DE (2014) Micelles, bicelles, amphipols, nanodiscs, liposomes or intact cells: the hitch-hiker guide to the study of membrane proteins by NMR. In: Mus-Veteau I (ed) Membrane protein production for structural analysis. Springer, New York (in press)Google Scholar
  21. Champeil P, Menguy T, Tribet C, Popot J-L, le Maire M (2000) Interaction of amphipols with the sarcoplasmic reticulum Ca2+-ATPase. J Biol Chem 275:18623–18637PubMedGoogle Scholar
  22. Charvolin D, Perez J-B, Rouvière F, Giusti F, Bazzacco P, Abdine A, Rappaport F, Martinez KL, Popot J-L (2009) The use of amphipols as universal molecular adapters to immobilize membrane proteins onto solid supports. Proc Natl Acad Sci USA 106:405–410PubMedGoogle Scholar
  23. Charvolin D, Picard M, Huang L-S, Berry EA, Popot J-L (2014) Solution behavior and crystallization of cytochrome bc1 in the presence of amphipols. J Membr Biol. doi: 10.1007/s00232-014-9694-4 PubMedGoogle Scholar
  24. Cherezov V (2011) Lipidic cubic phase technologies for membrane protein structural studies. Curr Opin Struct Biol 21:559–566PubMedPubMedCentralGoogle Scholar
  25. Cherezov V, Clogston J, Papiz MZ, Caffrey M (2006) Room to move: crystallizing membrane proteins in swollen lipidic mesophases. J Mol Biol 357:1605–1618PubMedGoogle Scholar
  26. Christman KL, Enriquez-Rios VD, Maynard HD (2006) Nanopatterning proteins and peptides. Soft Matter 2:928–939Google Scholar
  27. Coyer SR, García AJ, Delamarche E (2007) Facile preparation of complex protein architectures with sub-100-nm resolution on surfaces. Angew Chem Int Ed 46:6837–6840Google Scholar
  28. Cvetkov TL, Huynh KW, Cohen MR, Moiseenkova-Bell VY (2011) Molecular architecture and subunit organization of TRPA1 ion channel revealed by electron microscopy. J Biol Chem 286:38168–38176PubMedPubMedCentralGoogle Scholar
  29. Dahmane T, Damian M, Mary S, Popot J-L, Banères J-L (2009) Amphipol-assisted in vitro folding of G protein-coupled receptors. Biochemistry 48:6516–6521PubMedGoogle Scholar
  30. Dahmane T, Giusti F, Catoire LJ, Popot J-L (2011) Sulfonated amphipols: synthesis, properties and applications. Biopolymers 95:811–823PubMedGoogle Scholar
  31. Dahmane T, Rappaport F, Popot J-L (2013) Amphipol-assisted folding of bacteriorhodopsin in the presence and absence of lipids Functional consequences. Eur Biophys J 42:85–101PubMedGoogle Scholar
  32. Damian M, Marie J, Leyris J-P, Fehrentz J-A, Verdié P, Martinez J, Banères J-L, Mary S (2012) High constitutive activity is an intrinsic feature of ghrelin receptor protein: a study with a functional monomeric GHS-R1a receptor reconstituted in lipid discs. J Biol Chem 287:3630–3641PubMedGoogle Scholar
  33. Della Pia EA, Holm J, Lloret N, Le Bon C, Popot J-L, Zoonens M, Nygård J, Martinez KL (2014a) A step closer to membrane protein multiplexed nano-arrays using biotin-doped polypyrrole. ACS Nano 8:1844–1853PubMedPubMedCentralGoogle Scholar
  34. Della Pia EA, Westh Hansen R, Zoonens M, Martinez KL (2014b) Functionalized amphipols: a versatile toolbox suitable for applications of membrane proteins in synthetic biology. J Membr Biol. doi: 10.1007/s00232-014-9663-y PubMedGoogle Scholar
  35. Diab C, Tribet C, Gohon Y, Popot J-L, Winnik FM (2007a) Complexation of integral membrane proteins by phosphorylcholine-based amphipols. Biochim Biophys Acta 1768:2737–2747PubMedGoogle Scholar
  36. Diab C, Winnik FM, Tribet C (2007b) Enthalpy of interaction and binding isotherms of non-ionic surfactants onto micellar amphiphilic polymers (amphipols). Langmuir 23:3025–3035PubMedGoogle Scholar
  37. Duarte AMS, Wolfs CJAM, Koehorsta RBM, Popot J-L, Hemminga MA (2008) Solubilization of V-ATPase transmembrane peptides by amphipol A8-35. J Peptide Chem 14:389–393Google Scholar
  38. Duval-Terrié C, Cosette P, Molle G, Muller G, Dé E (2003) Amphiphilic biopolymers (amphibiopols) as new surfactants for membrane protein solubilization. Protein Sci 12:681–689PubMedPubMedCentralGoogle Scholar
  39. Elter S, Raschle T, Arens S, Gelev V, Etzkorn M, Wagner G (2014) The use of amphipols for NMR structural characterization of 7-TM proteins. J Membr Biol. doi: 10.1007/s00232-014-9669-5 PubMedPubMedCentralGoogle Scholar
  40. Etzkorn M, Raschle T, Hagn F, Gelev V, Rice AJ, Walz T, Wagner G (2013) Cell-free expressed bacteriorhodopsin in different soluble membrane mimetics: biophysical properties and NMR accessibility. Structure 21:394–401PubMedPubMedCentralGoogle Scholar
  41. Etzkorn M, Zoonens M, Catoire LJ, Popot J-L, Hiller S (2014) How amphipols embed membrane proteins: global solvent accessibility and interaction with a flexible protein terminus. J Membr Biol. doi: 10.1007/s00232-014-9657-9 PubMedGoogle Scholar
  42. Feinstein HE, Tifrea D, Popot J-L, de la Maza LM, Cocco MJ (2014) Long-term stability of a vaccine formulated with the amphipol-trapped major outer membrane protein from Chlamydia trachomatis. J Membr Biol. doi: 10.1007/s00232-014-9693-5 PubMedPubMedCentralGoogle Scholar
  43. Fernandez A, Le Bon C, Baumlin N, Giusti F, Crémel G, Popot J-L, Bagnard D (2014) In vivo characterization of the biodistribution profile of amphipols. J Membr Biol. doi: 10.1007/s00232-014-9682-8 PubMedPubMedCentralGoogle Scholar
  44. Ferrandez Y, Dezi M, Bosco M, Urvoas A, Valério M, Le Bon C, Giusti F, Broutin I, Durand G, Polidori A, Popot J-L, Picard M, Minard P (2014) Amphipol-mediated screening of molecular orthoses specific for membrane protein targets. J Membr Biol (this issue)Google Scholar
  45. Flötenmeyer M, Weiss H, Tribet C, Popot J-L, Leonard K (2007) The use of amphipathic polymers for cryo-electron microscopy of NADH: ubiquinone oxidoreductase (Complex I). J Microsc 227:229–235PubMedGoogle Scholar
  46. Giusti F, Popot J-L, Tribet C (2012) Well-defined critical association concentration and rapid adsorption at the air/water interface of a short amphiphilic polymer, amphipol A8-35: a study by Förster resonance energy transfer and dynamic surface tension measurements. Langmuir 28:10372–10380PubMedGoogle Scholar
  47. Giusti F, Kessler P, Westh Hansen R, Della Pia EA, Le Bon C, Mourier G, Popot J-L, Martinez KL, Zoonens M (2014a) Synthesis of a polyhistidine-bearing amphipol and its use for immobilization of membrane proteins (in preparation)Google Scholar
  48. Giusti F, Rieger J, Catoire L, Qian S, Calabrese AN, Watkinson TG, Casiraghi M, Radford SE, Ashcroft AE, Popot J-L (2014b) Synthesis, characterization and applications of a perdeuterated amphipol. J Membr Biol. doi: 10.1007/s00232-014-9656-x PubMedGoogle Scholar
  49. Gohon Y (1996) Etude des interactions entre un analogue du fragment transmembranaire de la glycophorine A et des polymères amphiphiles: les amphipols, DEA Thesis, Université Paris VI, Paris, 28 pGoogle Scholar
  50. Gohon Y, Popot J-L (2003) Membrane protein-surfactant complexes. Curr Opin Colloid Interface Sci 8:15–22Google Scholar
  51. Gohon Y, Pavlov G, Timmins P, Tribet C, Popot J-L, Ebel C (2004) Partial specific volume and solvent interactions of amphipol A8-35. Anal Biochem 334:318–334PubMedGoogle Scholar
  52. Gohon Y, Giusti F, Prata C, Charvolin D, Timmins P, Ebel C, Tribet C, Popot J-L (2006) Well-defined nanoparticles formed by hydrophobic assembly of a short and polydisperse random terpolymer, amphipol A8-35. Langmuir 22:1281–1290PubMedGoogle Scholar
  53. Gohon Y, Dahmane T, Ruigrok R, Schuck P, Charvolin D, Rappaport F, Timmins P, Engelman DM, Tribet C, Popot J-L, Ebel C (2008) Bacteriorhodopsin/amphipol complexes: structural and functional properties. Biophys J 94:3523–3537PubMedPubMedCentralGoogle Scholar
  54. Gohon Y, Vindigni J-D, Pallier A, Wien F, Celia H, Giuliani A, Tribet C, Chardot T, Briozzo P (2011) High water solubility and fold in amphipols of proteins with large hydrophobic regions: oleosins and caleosin from seed lipid bodies. Biochim Biophys Acta 1808:706–716PubMedGoogle Scholar
  55. Goluch ED, Shaw AW, Sligar SG, Liu C (2008) Microfluidic patterning of nanodisc lipid bilayers and multiplexed analysis of protein interaction. Lab Chip 8:1723–1728PubMedGoogle Scholar
  56. Gorzelle BM, Hoffman AK, Keyes MH, Gray DN, Ray DG, Sanders CR II (2002) Amphipols can support the activity of a membrane enzyme. J Am Chem Soc 124:11594–11595PubMedGoogle Scholar
  57. Guild K, Zhang Y, Stacy R, Mundt E, Benbow S, Green A, Myler PJ (2011) Wheat germ cell-free expression system as a pathway to improve protein yield and solubility for the SSGCID pipeline. Acta Crystallogr F 67:1027–1031Google Scholar
  58. Harris NJ, Booth PJ (2012) Folding and stability of membrane transport proteins in vitro. Biochim Biophys Acta 1818:1055–1066PubMedGoogle Scholar
  59. Henderson R (2013) Ion channel seen by electron microscopy. Nature 504:93–94PubMedGoogle Scholar
  60. Hopper JTS, Yu YT-C, Li D, Raymond A, Bostock M, Liko I, Mikhailov V, Laganowsky A, Benesch JLP, Caffrey M, Nietlispach D, Robinson CV (2013) Detergent-free mass spectrometry of membrane protein complexes. Nat. Meth. 10:1206–1208Google Scholar
  61. Huynh KW, Cohen MR, Moiseenkova-Bell VY (2014) Application of amphipols for structure-functional analysis of TRP channels. J Membr Biol. doi: 10.1007/s00232-014-9684-6 PubMedPubMedCentralGoogle Scholar
  62. Jamshad M, Lin YP, Knowles TJ, Parslow RA, Harris C, Wheatley M, Poyner DR, Bill RM, Thomas OR, Overduin M, Dafforn TR (2011) Surfactant-free purification of membrane proteins with intact native membrane environment. Biochem Soc Trans 39:813–818PubMedGoogle Scholar
  63. Katzen F, Peterson TC, Kudlicki W (2009) Membrane protein expression: no cells required. Trends Biotechnol 27:455–460PubMedGoogle Scholar
  64. Kevany BM, Tsybovsky Y, Campuzano IDG, Schnier PD, Engel A, Palczewski K (2013) Structural and functional analysis of the native peripherin-ROM1 complex isolated from photoreceptor cells. J Biol Chem 288:36272–36284PubMedPubMedCentralGoogle Scholar
  65. Kievit O, Brudvig GW (2001) Direct electrochemistry of photosystem I. J Electroanal Chem 497:139–149Google Scholar
  66. Klammt C, Schwarz D, Löhr F, Schneider B, Dötsch V, Bernhard F (2006) Cell-free expression as an emerging technique for the large scale production of integral membrane protein. FEBS J 273:4141–4153PubMedGoogle Scholar
  67. Klammt C, Perrin M-H, Maslennikov I, Renault L, Krupa M, Kwiatkowski W, Stahlberg H, Vale W, Choe S (2011) Polymer-based cell-free expression of ligand-binding family B G-protein coupled receptors without detergents. Protein Sci 20:1030–1041PubMedPubMedCentralGoogle Scholar
  68. Knowles TJ, Finka R, Smith C, Lin Y-P, Dafforn T, Overduin M (2009) Membrane proteins solubilized intact in lipid containing nanoparticles bounded by styrene maleic acid copolymer. J Am Chem Soc 131:7484–7485PubMedGoogle Scholar
  69. Kyrychenko A, Rodnin MV, Vargas MU, Sharma SK, Durand G, Pucci B, Popot J-L, Ladokhin AS (2012) Folding of diphteria toxin T-domain in the presence of amphipols and fluorinated surfactants: toward thermodynamic measurements of membrane protein folding. Biochim Biophys Acta 1818:1006–1012PubMedGoogle Scholar
  70. LaBean TM, Li H (2007) Constructing novel materials with DNA. Nano Today 2:26–35Google Scholar
  71. Ladavière C, Toustou M, Gulik-Krzywicki T, Tribet C (2001) Slow reorganization of small phosphatidylcholine vesicles upon adsorption of amphiphilic polymers. J Colloid Interface Sci 241:178–187PubMedGoogle Scholar
  72. Ladavière C, Tribet C, Cribier S (2002) Lateral organization of lipid membranes induced by amphiphilic polymer inclusions. Langmuir 18:7320–7327Google Scholar
  73. Laursen T, Naur P, Møller BL (2013) Amphipol trapping of a functional CYP system. Biotechnol Appl Biochem 60:119–127PubMedGoogle Scholar
  74. Le Bon C, Della Pia EA, Giusti F, Lloret N, Zoonens M, Martinez KL, Popot J-L (2014a) Synthesis of an oligonucleotide-derivatized amphipol and its use to trap and immobilize membrane proteins. Nucleic Acids Res. doi: 10.1093/nar/gku250 PubMedGoogle Scholar
  75. Le Bon C, Popot J-L, Giusti F (2014b) Labeling and functionalizing amphipols for biological applications. J Membr Biol. doi: 10.1007/s00232-014-9655-y PubMedGoogle Scholar
  76. Leney AC, McMorran LM, Radford SE, Ashcroft AE (2012) Amphipathic polymers enable the study of functional membrane proteins in the gas phase. Anal Chem 84:9841–9847PubMedPubMedCentralGoogle Scholar
  77. Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:107–112PubMedPubMedCentralGoogle Scholar
  78. Liao M, Cao E, Julius D, Cheng Y (2014) Single particle electron cryo-microscopy of a mammalian ion channel. Curr Opin Struct Biol 27:1–7PubMedGoogle Scholar
  79. Liu RCW, Pallier A, Brestaz M, Pantoustier N, Tribet C (2007) Impact of polymer microstructure on the self-assembly of amphiphilic polymers in aqueous solutions. Macromolecules 40:4276–4286Google Scholar
  80. Long AR, O’Brien CC, Malhotra K, Schwall CT, Albert AD, Watts A, Alder NN (2013) A detergent-free strategy for the reconstitution of active enzyme complexes from native biological membranes into nanoscale discs. BMC Biotechnol 13:41. doi: 10.1186/1472-6750-13-41 PubMedPubMedCentralGoogle Scholar
  81. Luccardini C, Tribet C, Vial F, Marchi-Artzner V, Dahan M (2006) Size, charge, and interactions with giant lipid vesicles of quantum dots coated with an amphiphilic macromolecule. Langmuir 22:2304–2310PubMedGoogle Scholar
  82. Lyukmanova EN, Shenkarev ZO, Khabibullina NF, Kopeina GS, Shulepko MA, Paramonov AS, Mineev KS, Tikhonov RV, Shingarova LN, Petrovskaya LE, Dolgikh DA, Arseniev AS, Kirpichnikov MP (2012) Lipid–protein nanodiscs for cell-free production of integral membrane proteins in a soluble and folded state: comparison with detergent micelles, bicelles and liposomes. Biochim Biophys Acta 1818:349–358PubMedGoogle Scholar
  83. Ma D, Martin N, Herbet A, Boquet D, Tribet C, Winnik FM (2012) The thermally induced aggregation of immunoglobulin G in solution is prevented by amphipols. Chem Lett 41:1380–1382Google Scholar
  84. Magny B, Lafuma F, Iliopoulos I (1992) Determination of microstructure of hydrophobically modified water-soluble polymers by 13C NMR. Polymer 33:3151–3154Google Scholar
  85. Marie E, Sagan S, Cribier S, Tribet C (2014) Amphiphilic macromolecules on cell membranes: from protective layers to controlled permeabilization. J Membr Biol. doi: 10.1007/s00232-014-9679-3 PubMedGoogle Scholar
  86. Martinez KL, Gohon Y, Corringer P-J, Tribet C, Mérola F, Changeux J-P, Popot J-L (2002) Allosteric transitions of Torpedo acetylcholine receptor in lipids, detergent and amphipols: molecular interactions vs. physical constraints. FEBS Lett 528:251–256PubMedGoogle Scholar
  87. Mary S, Damian M, Rahmeh R, Marie J, Mouillac B, Banères J-L (2014) Amphipols in G protein-coupled receptor pharmacology: What are they good for? J Membr Biol. doi: 10.1007/s00232-014-9665-9 PubMedGoogle Scholar
  88. Merino JM, Møller JV, Gutiérrez-Merino C (1994) Thermal unfolding of monomeric Ca2+, Mg2+-ATPase from sarcoplasmic reticulum of rabbit skeletal muscle. FEBS Lett 343:155–159PubMedGoogle Scholar
  89. Nagy JK, Kuhn Hoffmann A, Keyes MH, Gray DN, Oxenoid K, Sanders CR (2001) Use of amphipathic polymers to deliver a membrane protein to lipid bilayers. FEBS Lett 501:115–120PubMedGoogle Scholar
  90. Nath A, Atkins WM, Sligar SG (2007) Applications of phospholipid bilayer nanodiscs in the study of membranes and membrane proteins. Biochemistry 46:2059–2069PubMedGoogle Scholar
  91. Ning Z, Seebun D, Hawley B, Chang C-K, Figeys D (2013) From cells to peptides: “One-stop” integrated proteomic processing using amphipols. J Proteome Res 12:1512–1519PubMedGoogle Scholar
  92. Ning Z, Hawley B, Seebun D, Figeys D (2014) APols aided protein precipitation: a rapid method for protein concentrating for proteomic analysis. J Membr Biol. doi: 10.1007/s00232-014-9668-6 PubMedPubMedCentralGoogle Scholar
  93. Nowaczyk M, Oworah-Nkruma R, Zoonens M, Rögner M, Popot J-L (2004) Amphipols: strategies for an improved PS2 environment in aqueous solution. In: Miyake J (ed) Biohydrogen III. Elsevier, Dordrecht, pp 151–159Google Scholar
  94. Opačić M, Giusti F, Broos J, Popot J-L (2014a) Amphipol A8-35 preserves the activity of detergent-sensitive mutants of Escherichia coli mannitol permease EIImtl. J Membr Biol.  10.1007/s00232-014-9691-7
  95. Opačić M, Durand G, Bosco M, Polidori A, Popot J-L, (2014b). Amphipols and photosynthetic light-harvesting pigment-protein complexes. J Membr Biol (this issue)Google Scholar
  96. Orwick MC, Judge PJ, Procek J, Lindholm L, Graziadei A, Engel A, Grobner G, Watts A (2012) Detergent-free formation and physicochemical characterization of nanosized lipid–polymer complexes. Angew Chem Int Ed 51:4653–4657Google Scholar
  97. Orwick-Rydmark M, Lovett JE, Graziadei A, Lindholm L, Hicks MR, Watts A (2012) Detergent-free incorporation of a seven-transmembrane receptor protein into nanosized bilayer Lipodisq particles for functional and biophysical studies. Nano Lett 12:4687–4692PubMedGoogle Scholar
  98. Otzen DE, Andersen KK (2013) Folding of outer membrane proteins. Arch Biochem Biophys 531:34–43PubMedGoogle Scholar
  99. Park K-H, Berrier C, Lebaupain F, Pucci B, Popot J-L, Ghazi A, Zito F (2007) Fluorinated and hemifluorinated surfactants as alternatives to detergents for membrane protein cell-free synthesis. Biochem J 403:183–187PubMedPubMedCentralGoogle Scholar
  100. Park K-H, Billon-Denis E, Dahmane T, Lebaupain F, Pucci B, Breyton C, Zito F (2011) In the cauldron of cell-free synthesis of membrane proteins: playing with new surfactants. New Biotechnol 28:255–261Google Scholar
  101. Perlmutter JD, Drasler WJ, Xie W, Gao J, Popot J-L, Sachs JN (2011) All-atom and coarse-grained molecular dynamics simulations of a membrane protein stabilizing polymer. Langmuir 27:10523–10537PubMedPubMedCentralGoogle Scholar
  102. Perlmutter JD, Popot J-L, Sachs JN (2014) Molecular dynamics simulations of a membrane protein/amphipol complex. J Membr Biol. doi: 10.1007/s00232-014-9690-8 PubMedGoogle Scholar
  103. Picard M, Duval-Terrié C, Dé E, Champeil P (2004) Stabilization of membranes upon interaction of amphipathic polymers with membrane proteins. Protein Sci 13:3056–3058PubMedPubMedCentralGoogle Scholar
  104. Picard M, Dahmane T, Garrigos M, Gauron C, Giusti F, le Maire M, Popot J-L, Champeil P (2006) Protective and inhibitory effects of various types of amphipols on the Ca2+-ATPase from sarcoplasmic reticulum: a comparative study. Biochemistry 45:1861–1869PubMedGoogle Scholar
  105. Planchard N, Point E, Dahmane T, Giusti F, Renault M, Le Bon C, Durand G, Milon A, Guittet E, Zoonens M, Popot J-L, Catoire LJ (2014) The use of amphipols for solution NMR studies of membrane proteins: advantages and limitations as compared to other solubilizing media. J Membr Biol. doi: 10.1007/s00232-014-9654-z PubMedGoogle Scholar
  106. Pocanschi CL, Dahmane T, Gohon Y, Rappaport F, Apell H-J, Kleinschmidt JH, Popot J-L (2006) Amphipathic polymers: tools to fold integral membrane proteins to their active form. Biochemistry 45:13954–13961PubMedGoogle Scholar
  107. Pocanschi C, Popot J-L, Kleinschmidt JH (2013) Folding and stability of outer membrane protein A (OmpA) from Escherichia coli in an amphipathic polymer, amphipol A8-35. Eur Biophys J 42:103–118PubMedGoogle Scholar
  108. Polovinkin V, Balandin T, Volkov O, Round E, Borshchevskiy V, Utrobin P, von Stetten D, Royant A, Willbold D, Arzumanyan A, Popot J-L, Gordeliy V (2014a) Nanoparticle surface-enhanced Raman scattering of bacteriorhodopsin stabilized by amphipol A8-35. J Membr Biol. doi: 10.1007/s00232-014-9701-9 PubMedGoogle Scholar
  109. Polovinkin V, Gushchin I, Sintsov M, Round E, Balandin T, Chervakov P, Schevchenko V, Utrobin P, Popov A, Borshchevskiy V, Mishin A, Kuklin A, Willbold D, Popot J-L, Gordeliy V (2014b) High-resolution structure of a membrane protein transferred from amphipol to a lipidic mesophase. J Membr Biol. doi: 10.1007/s00232-014-9700-x PubMedGoogle Scholar
  110. Popot J-L (2010) Amphipols, nanodiscs, and fluorinated surfactants: three non-conventional approaches to studying membrane proteins in aqueous solutions. Annu Rev Biochem 79:737–775PubMedGoogle Scholar
  111. Popot J-L (2014) Folding membrane proteins in vitro: a table and some comments. Arch Biochem Biophys (in press)Google Scholar
  112. Popot J-L, Engelman DM (2014) The paradox of membrane proteins folding in the absence of a membrane (in preparation)Google Scholar
  113. Popot J-L, Kleinschmidt JH (2014) Stabilization and folding of integral membrane proteins by amphipols (in preparation)Google Scholar
  114. Popot J-L, Berry EA, Charvolin D, Creuzenet C, Ebel C, Engelman DM, Flötenmeyer M, Giusti F, Gohon Y, Hervé P, Hong Q, Lakey JH, Leonard K, Shuman HA, Timmins P, Warschawski DE, Zito F, Zoonens M, Pucci B, Tribet C (2003) Amphipols: polymeric surfactants for membrane biology research. Cell Mol Life Sci 60:1559–1574PubMedGoogle Scholar
  115. Popot J-L, Althoff T, Bagnard D, Banères J-L, Bazzacco P, Billon-Denis E, Catoire LJ, Champeil P, Charvolin D, Cocco MJ, Crémel G, Dahmane T, de la Maza LM, Ebel C, Gabel F, Giusti F, Gohon Y, Goormaghtigh E, Guittet E, Kleinschmidt JH, Kühlbrandt W, Le Bon C, Martinez KL, Picard M, Pucci B, Rappaport F, Sachs JN, Tribet C, van Heijenoort C, Wien F, Zito F, Zoonens M (2011) Amphipols from A to Z. Annu Rev Biophys 40:379–408PubMedGoogle Scholar
  116. Prassl R, Laggner P (2009) Molecular structure of low density lipoprotein: current status and future challenges. Eur Biophys J 38:145–158PubMedGoogle Scholar
  117. Prata C, Giusti F, Gohon Y, Pucci B, Popot J-L, Tribet C (2001) Non-ionic amphiphilic polymers derived from tris(hydroxymethyl)-acrylamidomethane keep membrane proteins soluble and native in the absence of detergent. Biopolymers 56:77–84Google Scholar
  118. Privé GG (2007) Detergents for the stabilization and crystallization of membrane proteins. Methods 41:388–397PubMedGoogle Scholar
  119. Privé G (2009) Lipopeptide detergents for membrane protein studies. Curr Opin Struct Biol 19:1–7Google Scholar
  120. Qi L, Gao X (2008) Quantum dot-amphipol nanocomplex for intracellular delivery and real-time imaging of siRNA. ACS Nano 2:1403–1410PubMedPubMedCentralGoogle Scholar
  121. Qi L, Wu L, Zheng S, Wang Y, Fu H, Cui D (2012) Cell-penetrating magnetic nanoparticles for highly efficient delivery and intracellular imaging of siRNA. Biomacromolecules 13:2723–2730PubMedGoogle Scholar
  122. Rahmeh R, Damian M, Cottet M, Orcel H, Mendre C, Durroux T, Sharma KS, Durand G, Pucci B, Trinquet E, Zwier JM, Deupi X, Bron P, Banères J-L, Mouillac B, Granier S (2012) Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy. Proc Natl Acad Sci USA 109:6733–6738PubMedGoogle Scholar
  123. Rajesh S, Knowles TJ, Overduin M (2011) Production of membrane proteins without cells or detergents. New Biotechnol 28:250–254Google Scholar
  124. Raschle T, Hiller S, Etzkorn M, Wagner G (2010) Nonmicellar systems for solution NMR spectroscopy of membrane proteins. Curr Opin Struct Biol 20:471–479PubMedPubMedCentralGoogle Scholar
  125. Renault M (2008) Etudes structurales et dynamiques de la protéine membranaire KpOmpA par RMN en phase liquide et solide. Ph. D. Thesis, Université Paul Sabatier, Toulouse, 180 pGoogle Scholar
  126. Sahu ID, McCarrick RM, Troxel KR, Zhang R, Smith HJ, Dunagan MM, Swartz MS, Rajan PV, Kroncke BM, Sanders CR, Lorigan GA (2013) DEER EPR measurements for membrane protein structures via bifunctional spin labels and lipodisq nanoparticles. Biochemistry 52:6627–6632PubMedGoogle Scholar
  127. Sanders CR, Hoffmann AK, Gray DN, Keyes MH, Ellis CD (2004) French swimwear for membrane proteins. ChemBioChem 5:423–426PubMedGoogle Scholar
  128. Shadiac N, Nagarajan Y, Waters S, Hrmova M (2013) Close allies in membrane protein research: cell-free synthesis and nanotechnology. Mol Membr Biol 30:229–245PubMedGoogle Scholar
  129. Sharma KS, Durand G, Giusti F, Olivier B, Fabiano A-S, Bazzacco P, Dahmane T, Ebel C, Popot J-L, Pucci B (2008) Glucose-based amphiphilic telomers designed to keep membrane proteins soluble in aqueous solutions: synthesis and physicochemical characterization. Langmuir 24:13581–13590PubMedGoogle Scholar
  130. Sharma KS, Durand G, Gabel F, Bazzacco P, Le Bon C, Billon-Denis E, Catoire LJ, Popot J-L, Ebel C, Pucci B (2012) Non-ionic amphiphilic homopolymers: synthesis, solution properties, and biochemical validation. Langmuir 28:4625–4639PubMedGoogle Scholar
  131. Shaw AW, Pureza VS, Sligar SG, Morrissey JH (2007) The local phospholipid environment modulates the activation of blood clotting. J Biol Chem 282:6556–6563PubMedGoogle Scholar
  132. Shenkarev ZO, Lyukmanova EN, Butenko IO, Petrovskaya LE, Paramonov AS, Shulepko MA, Nekrasova OV, Kirpichnikov MP, Arseniev AS (2013) Lipid–protein nanodiscs promote in vitro folding of transmembrane domains of multi-helical and multimeric membrane proteins. Biochim Biophys Acta 1828:776–784PubMedGoogle Scholar
  133. Sverzhinsky A, Qian S, Yang L, Allaire M, Moraes I, Ma D, Chung JW, Zoonens M, Popot J-L, Coulton JW (2014) Amphipol-trapped ExbB–ExbD membrane protein complex from Escherichia coli: A biochemical and structural case study. J Membr Biol. doi: 10.1007/s0032-014-9678-4
  134. Swift J (1726) Travels into Several Remote Nations of the World. In Four Parts. By Lemuel Gulliver, first a surgeon, and then a captain of several ships Benjamin Motte, LondonGoogle Scholar
  135. Tehei M, Perlmutter J, Giusti F, Sachs J, Zaccai G, Popot J-L (2014) Thermal fluctuations in amphipol A8-35 measured by neutron scattering. J Membr Biol (this issue)Google Scholar
  136. Tifrea DF, Sun G, Pal S, Zardeneta G, Cocco MJ, Popot J-L, de la Maza LM (2011) Amphipols stabilize the Chlamydia major outer membrane protein and enhance its protective ability as a vaccine. Vaccine 29:4623–4631PubMedPubMedCentralGoogle Scholar
  137. Tifrea D, Pal S, Cocco MJ, Popot J-L, de la Maza LM (2014) Increased immuno accessibility of MOMP epitopes in a vaccine formulated with amphipols may account for the very robust protection elicited against a vaginal challenge with C. muridarum. J Immunol 192:5201–5213Google Scholar
  138. Tribet C, Vial F (2008) Flexible macromolecules attached to lipid bilayers: impact on fluidity, curvature, permeability and stability of the membranes. Soft Matter 4:68–81Google Scholar
  139. Tribet C, Audebert R, Popot J-L (1996) Amphipols: polymers that keep membrane proteins soluble in aqueous solutions. Proc Natl Acad Sci USA 93:15047–15050PubMedGoogle Scholar
  140. Tribet C, Audebert R, Popot J-L (1997) Stabilization of hydrophobic colloidal dispersions in water with amphiphilic polymers: application to integral membrane proteins. Langmuir 13:5570–5576Google Scholar
  141. Tribet C, Mills D, Haider M, Popot J-L (1998) Scanning transmission electron microscopy study of the molecular mass of amphipol/cytochrome b 6 f complexes. Biochimie 80:475–482PubMedGoogle Scholar
  142. Tribet C, Diab C, Dahmane T, Zoonens M, Popot J-L, Winnik FM (2009) Thermodynamic characterization of the exchange of detergents and amphipols at the surfaces of integral membrane proteins. Langmuir 25:12623–12634PubMedGoogle Scholar
  143. Tsybovsky Y, Orban T, Molday RS, Taylor D, Palczewski K (2013) Molecular organization and ATP-induced conformational changes of ABCA4, the photoreceptor-specific ABC transporter. Structure 21:854–860PubMedPubMedCentralGoogle Scholar
  144. Udi Y, Fragai M, Grossman M, Mitternacht S, Arad-Yellin R, Calderone V, Melikian M, Toccafondi M, Berezovsky IN, Luchinat C, Sagi I (2013) Unraveling hidden regulatory sites in structurally homologous metalloproteases. J Mol Biol 425:2330–2346PubMedGoogle Scholar
  145. Vahedi-Faridi A, Jastrzebska B, Palczewski K, Engel A (2013) 3D imaging and quantitative analysis of small solubilized membrane proteins and their complexes by transmission electron microscopy. Microscopy 62:95–107PubMedPubMedCentralGoogle Scholar
  146. Vial F, Rabhi S, Tribet C (2005) Association of octyl-modified poly(acrylic acid) onto unilamellar vesicles of lipids and kinetics of vesicle disruption. Langmuir 21:853–862PubMedGoogle Scholar
  147. Vial F, Oukhaled AG, Auvray L, Tribet C (2007) Long-living channels of well defined radius opened in lipid bilayers by polydisperse, hydrophobically-modified polyacrylic acids. Soft Matter 3:75–78Google Scholar
  148. Vial F, Cousin F, Bouteiller L, Tribet C (2009) Rate of permeabilization of giant vesicles by amphiphilic polyacrylates compared to the adsorption of these polymers onto large vesicles and tethered lipid bilayers. Langmuir 25:7506–7513PubMedGoogle Scholar
  149. Warschawski DE, Arnold AA, Beaugrand M, Gravel A, Chartrand E, Marcotte I (2011) Choosing membrane mimetics for NMR structural studies of transmembrane proteins. Biochim Biophys Acta 1808:1957–1974PubMedGoogle Scholar
  150. Wingren C, Borrebaeck CA (2007) Progress in miniaturization of protein arrays-a step closer to high-density nanoarrays. Drug Discov Today 12:813–818PubMedGoogle Scholar
  151. Wolff N, Delepierre M (1997) Conformation of the C-terminal secretion signal of the Serratia marcescens haem acquisition protein (HasA) in amphipols solution, a new class of surfactant. J Chim Phys 95:437–442Google Scholar
  152. Zoonens M (2004) Caractérisation des complexes formés entre le domaine transmembranaire de la protéine OmpA et des polymères amphiphiles, les amphipols. Application à l’étude structurale des protéines membranaires par RMN à haute résolution. Ph. D. Thesis, Paris-6, Paris, 233 pGoogle Scholar
  153. Zoonens M, Catoire LJ, Giusti F, Popot J-L (2005) NMR study of a membrane protein in detergent-free aqueous solution. Proc Natl Acad Sci USA 102:8893–8898PubMedGoogle Scholar
  154. Zoonens M, Giusti F, Zito F, Popot J-L (2007) Dynamics of membrane protein/amphipol association studied by Förster resonance energy transfer. Implications for in vitro studies of amphipol-stabilized membrane proteins. Biochemistry 46:10392–10404PubMedGoogle Scholar
  155. Zoonens M, Zito F, Martinez KL, Popot J-L (2014) Amphipols: a general introduction and some protocols. In: Mus-Veteau I (ed) Membrane protein production for structural analysis. Springer, New York (in press)Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Laboratoire de Physico-Chimie Moléculaire des Protéines MembranairesUMR 7099, Institut de Biologie Physico-Chimique (FRC 550), Centre National de la Recherche Scientifique/Université Paris-7ParisFrance

Personalised recommendations