The Journal of Membrane Biology

, Volume 247, Issue 9–10, pp 861–881 | Cite as

Amphiphilic Macromolecules on Cell Membranes: From Protective Layers to Controlled Permeabilization

  • E. Marie
  • S. Sagan
  • S. Cribier
  • C. TribetEmail author


Antimicrobial and cell-penetrating peptides have inspired developments of abiotic membrane-active polymers that can coat, penetrate, or break lipid bilayers in model systems. Application to cell cultures is more recent, but remarkable bioactivities are already reported. Synthetic polymer chains were tailored to achieve (i) high biocide efficiencies, and selectivity for bacteria (Gram-positive/Gram-negative or bacterial/mammalian membranes), (ii) stable and mild encapsulation of viable isolated cells to escape immune systems, (iii) pH-, temperature-, or light-triggered interaction with cells. This review illustrates these recent achievements highlighting the use of abiotic polymers, and compares the major structural determinants that control efficiency of polymers and peptides. Charge density, sp. of cationic and guanidinium side groups, and hydrophobicity (including polarity of stimuli-responsive moieties) guide the design of new copolymers for the handling of cell membranes. While polycationic chains are generally used as biocidal or hemolytic agents, anionic amphiphilic polymers, including Amphipols, are particularly prone to mild permeabilization and/or intracell delivery.


Amphiphilic polymers Amphipols Antimicrobial and cell penetrating peptides Cell membrane permeabilization 



EM and CT were supported by “programme Investissement d’Avenir ANR-11-LABX-0011-01.”


  1. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65(1):36–48PubMedGoogle Scholar
  2. Alves ID, Bechara C, Walrant A, Zaltsman Y, Jiao CY, Sagan S (2011a) Relationships between membrane binding, affinity and cell internalization efficacy of a cell-penetrating peptide: penetratin as a case study. PLoS ONE 6(9):e24096PubMedPubMedCentralGoogle Scholar
  3. Alves ID, Rodriguez N, Cribier S, Sagan S (2011b) Membrane crossover by cell-penetrating peptides: kinetics and mechanisms—from model to cell membrane perturbation by permeant peptides. Fundam Biomed Technol 5:179–196Google Scholar
  4. Amado E, Kerth A, Blume A, Kressler J (2008) Infrared reflection absorption spectroscopy coupled with Brewster angle microscopy for studying interactions of amphiphilic triblock copolymers with phospholipid monolayers. Langmuir 24(18):10041–10053PubMedGoogle Scholar
  5. Amado E, Kerth A, Blume A, Kressler J (2009) Phospholipid crystalline clusters induced by adsorption of novel amphiphilic triblock copolymers to monolayers. Soft Matter 5(3):669–675Google Scholar
  6. Andaloussi SE, Lehto T, Lundin P, Langel U (2011) Application of PepFect peptides for the delivery of splice-correcting oligonucleotides. Methods Mol Biol 683:361–373PubMedGoogle Scholar
  7. Andreev OA, Karabadzhak AG, Weerakkody D, Andreev GO, Engelman DM, Reshetnyak YK (2010) pH (low) insertion peptide (pHLIP) inserts across a lipid bilayer as a helix and exits by a different path. Proc Natl Acad Sci USA 107(9):4081–4086PubMedGoogle Scholar
  8. Aroui S, Brahim S, De Waard M, Bréard J, Kenani A (2009) Efficient induction of apoptosis by doxorubicin coupled to cell-penetrating peptides compared to unconjugated doxorubicin in the human breast cancer cell line MDA-MB 231. Cancer Lett 285:28–38PubMedGoogle Scholar
  9. Avery CW, Palermo EF, McLaughin A, Kuroda K, Chen Z (2011) Investigations of the interactions between synthetic antimicrobial polymers and substrate-supported lipid bilayers using sum frequency generation vibrational spectroscopy. Anal Chem 83(4):1342–1349PubMedGoogle Scholar
  10. Ayame H, Morimoto N, Akiyoshi K (2008) Self-assembled cationic nanogels for intracellular protein delivery. Bioconj Chem 19(4):882–890Google Scholar
  11. Bechara C, Pallerla M, Zaltsman Y, Burlina F, Alves ID, Lequin O, Sagan S (2013) Tryptophan within basic peptide sequences triggers glycosaminoglycan-dependent endocytosis. FASEB J 27(2):738–749PubMedGoogle Scholar
  12. Bechinger B, Aisenbrey C (2012a) The polymorphic nature of membrane-active peptides from biophysical and structural investigations. Curr Protein Pept Sci 13(7):602–610PubMedGoogle Scholar
  13. Bechinger B, Aisenbrey C (2012b) The polymorphic nature of membrane-active peptides from biophysical and structural investigations. Curr Prot Peptide Sci 13(7):602–610Google Scholar
  14. Bechinger B, Zasloff M, Opella SJ (1993) Structure and orientation of the antibiotic peptide magainin in membranes by solid-state nuclear magnetic resonance spectroscopy. Protein Sci 2:2077–2084PubMedPubMedCentralGoogle Scholar
  15. Berlose JP, Convert O, Derossi D, Brunissen A, Chassaing G (1996) Conformational and associative behaviours of the third helic of antennapedia homeodomain in membrane-mimetic environments. Eur J Biochem 242:372–386PubMedGoogle Scholar
  16. Binder WH (2008) Polymer-induced transient pores in lipid membranes. Angew Chem-Int Edn 47(17):3092–3095Google Scholar
  17. Binder WH, Barragan V, Menger FM (2003) Domains and rafts in lipid membranes. Angew Chem-Int Edn 42(47):5802–5827Google Scholar
  18. Blume A, Kerth A (2013) Peptide and protein binding to lipid monolayers studied by FT-IRRA spectroscopy. Biochimica et Biophysica Acta-Biomembranes 1828(10):2294–2305Google Scholar
  19. Bode SA, Thévenin M, Bechara C, Sagan S, Bregant S, Lavielle S, Chassaing G, Burlina F (2012) Self-assembling mini cell-penetrating peptides enter by both direct translocation and glycosaminoglycan-dependent endocytosis. Chem Commun 48:7179–7181Google Scholar
  20. Brattwall CE, Lincoln P, Nordén B (2003) Orientation and conformation of cell-penetrating peptide penetratin in phospholipid vesicle membranes determined by polarized-light spectroscopy. JACS 125:14214–14215Google Scholar
  21. Chakrabarty S, King A, Kurt P, Zhang W, Ohman DE, Wood LF, Lovelace C, Rao R, Wynne KJ (2011) Highly effective, water-soluble, hemocompatible 1,3-propylene oxide-based antimicrobials: poly (3,3-quaternary/PEG)-copolyoxetanes. Biomacromolecules 12(3):757–769PubMedGoogle Scholar
  22. Chanana M, Gliozzi A, Diaspro A, Chodnevskaja I, Huewel S, Moskalenko V, Ulrichs K, Galla HJ, Krol S (2005) Interaction of polyelectrolytes and their composites with living cells. Nano Lett 5(12):2605–2612PubMedGoogle Scholar
  23. Chandaroy P, Sen A, Alexandridis P, Hui SW (2002) Utilizing temperature-sensitive association of Pluronic F-127 with lipid bilayers to control liposome-cell adhesion. Biochim Biophys Acta-Biomembr 1559(1):32–42Google Scholar
  24. Chen T, McIntosh D, He Y, Kim J, Tirrell DA, Scherrer P, Fenske DB, Sandhu AP, Cullis PR (2004) Alkylated derivatives of poly(ethylacrylic acid) can be inserted into preformed liposomes and trigger pH-dependent intracellular delivery of liposomal contents. Mol Membr Biol 21:385–393PubMedGoogle Scholar
  25. Chen R, Khormaee S, Eccleston ME, Slater NKH (2009) The role of hydrophobic amino acid grafts in the enhancement of membrane-disruptive activity of pH-responsive pseudo-peptides. Biomaterials 30(10):1954–1961PubMedPubMedCentralGoogle Scholar
  26. Christiaens B, Symoens S, Verheyden S, Engelborghs Y, Joliot A, Prochiantz A, Vandekerckhove J, Rosseneu M, Vanloo B (2002) Tryptophan fluorescence study of the interaction of penetratin peptides with model membranes. Eur J Biochem 269:2918–2926PubMedGoogle Scholar
  27. Console S, Marty C, Garcia-Echeverria C, Schwendener R, Ballmer-Hofer K (2003) Antennapedia and HIV transactivator of transcription (TAT) “protein transduction domains” promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans. J Biol Chem 278(37):35109–35114PubMedGoogle Scholar
  28. Cooley CB, Trantow BM, Nederberg F, Kiesewetter MK, Hedrick JL, Waymouth RM, Wender PA (2009) Oligocarbonate molecular transporters: oligomerization-based syntheses and cell-penetrating studies. J Am Chem Soc 131(45):16401PubMedPubMedCentralGoogle Scholar
  29. Couffin-Hoarau AC, Leroux JC (2004) Report on the use of poly(organophosphazenes) for the design of stimuli-responsive vesicles. Biomacromolecules 5(6):2082–2087PubMedGoogle Scholar
  30. Crombez L, Morris MC, Dufort S, Aldrian-Herrada G, Nguyen Q, Mc Master G, Coll JL, Heitz F, Divita G (2009) Targeting cyclin B1 through peptide-based delivery of siRNA prevents tumour growth. Nucleic Acids Res 37:4559–4569PubMedPubMedCentralGoogle Scholar
  31. De Koker S, Hoogenboom R, De Geest BG (2012) Polymeric multilayer capsules for drug delivery. Chem Soc Rev 41(7):2867–2884PubMedGoogle Scholar
  32. DeGrado WF, Musso GF, Lieber M, Kaiser ET, Kézdy FJ (1982) Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue. Biophys J 37:329–338PubMedPubMedCentralGoogle Scholar
  33. Delaroche D, Cantrelle FX, Subra F, Van Heijenoort C, Guittet E, Jiao CY, Blanchoin L, Chassaing G, Lavielle S, Auclair C, Sagan S (2010) Cell-penetrating peptides with intracellular actin-remodeling activity in malignant fibroblasts. J Biol Chem 285(10):7712–7721PubMedGoogle Scholar
  34. Demina T, Grozdova I, Krylova O, Zhirnov A, Istratov V, Frey H, Kautz H, Melik-Nubarov N (2005) Relationship between the structure of amphiphilic copolymers and their ability to disturb lipid bilayers. Biochemistry 44(10):4042–4054PubMedGoogle Scholar
  35. Derossi D, Joliot AH, Chassaing G, Prochiantz A (1994) the 3rd helix of the antennapedia homeodomain translocates through biological-membranes. J Biol Chem 269(14):10444–10450PubMedGoogle Scholar
  36. Deshayes S, Konate K, Rydstrom A, Crombez L, Godefroy C, Milhiet PE, Thomas A, Brasseur R, Aldrian G, Heitz F, Munoz-Morris MA, Devoisselle JM, Divita G (2012) Self-assembling peptide-based nanoparticles for siRNA delivery in primary cell lines. Small 8(14):2184–2188PubMedGoogle Scholar
  37. Devaraj NK, Thurber GM, Keliher EJ, Marinelli B, Weissleder R (2012) Reactive polymer enables efficient in vivo bioorthogonal chemistry. Proc Natl Acad Sci USA 109(13):4762–4767PubMedGoogle Scholar
  38. Diaspro A, Silvano D, Krol S, Cavalleri O, Gliozzi A (2002) Single living cell encapsulation in nano-organized polyelectrolyte shells. Langmuir 18(13):5047–5050Google Scholar
  39. Dizman B, Elasri MO, Mathias LJ (2004) Synthesis and antimicrobial activities of new water-soluble bis-quaternary ammonium methacrylate polymers. J Appl Polym Sci 94(2):635–642Google Scholar
  40. Doshi N, Swiston AJ, Gilbert JB, Alcaraz ML, Cohen RE, Rubner MF, Mitragotri S (2011) Cell-based drug delivery devices using phagocytosis-resistant backpacks. Adv Mater 23(12):H105–H109PubMedGoogle Scholar
  41. Eccleston ME, Kuiper M, Gilchrist FM, Slater NKH (2000) pH-responsive pseudo-peptides for cell membrane disruption. J Controlled Release 69(2):297–307Google Scholar
  42. Epand RF, Mor A, Epand RM (2011) Lipid complexes with cationic peptides and OAKs; their role in antimicrobial action and in the delivery of antimicrobial agents. Cell Mol Life Sci 68(13):2177–2188PubMedGoogle Scholar
  43. Fakhrullin RF, Zamaleeva AI, Morozov MV, Tazetdinova DI, Alimova FK, Hilmutdinov AK, Zhdanov RI, Kahraman M, Culha M (2009) Living fungi cells encapsulated in polyelectrolyte shells doped with metal nanoparticles. Langmuir 25(8):4628–4634PubMedGoogle Scholar
  44. Fakhrullin RF, Zamaleeva AI, Minullina RT, Konnova SA, Paunov VN (2012) Cyborg cells: functionalisation of living cells with polymers and nanomaterials. Chem Soc Rev 41(11):4189–4206PubMedGoogle Scholar
  45. Ferri JK, Miller R, Makievski AV (2005) Equilibrium and dynamics of PEO/PPO/PEO penetration into DPPC monolayers. Colloids Surfaces A 261(1–3):39–48Google Scholar
  46. Fillon YA, Anderson JP, Chmielewski J (2005) Cell penetrating agents based on a polyproline helix scaffold. J Am Chem Soc 127(33):11798–11803PubMedGoogle Scholar
  47. Firestone MA, Seifert S (2005) Interaction of nonionic PEO-PPO diblock copolymers with lipid bilayers. Biomacromolecules 6(5):2678–2687PubMedGoogle Scholar
  48. Fischer D, Li YX, Ahlemeyer B, Krieglstein J, Kissel T (2003) In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 24(7):1121–1131PubMedGoogle Scholar
  49. Francis MF, Dhara G, Winnik FM, Leroux JC (2001) In vitro evaluation of pH-sensitive polymer/niosome complexes. Biomacromolecules 2(3):741–749PubMedGoogle Scholar
  50. Franz B, Balkundi SS, Dahl C, Lvov YM, Prange A (2010) Layer-by-layer nano-encapsulation of microbes: controlled cell surface modification and investigation of substrate uptake in bacteria. Macromol Biosci 10(2):164–172PubMedGoogle Scholar
  51. Futaki S, Suzuki T, Ohashi W, Yagami T, Tanaka S, Ueda K, Sugiura Y (2001) Arginine-rich peptides—an abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem 276(8):5836–5840PubMedGoogle Scholar
  52. Futaki S, Nakase I, Suzuki T, Zhang YJ, Sugiura Y (2002) Translocation of branched-chain arginine peptides through cell membranes: flexibility in the spatial disposition of positive charges in membrane-permeable peptides. Biochemistry 41(25):7925–7930PubMedGoogle Scholar
  53. Gabriel GJ, Pool JG, Som A, Dabkowski JM, Coughlin EB, Muthukurnar M, Tew GN (2008) Interactions between antimicrobial polynorbornenes and phospholipid vesicles monitored by light scattering and microcalorimetry. Langmuir 24(21):12489–12495PubMedGoogle Scholar
  54. Garg P, Debnath T, Chelluri LK, Hebalkar N (2012) Feasibility of polymer based cell encapsulation using electrostatic layer by layer assembly. J Biomater Tissue Eng 2(3):215–219Google Scholar
  55. Georghiou S, Thompson M, Mukhopadhyay AK (1982) melittin-phospholipid interaction studied by employing the single tryptophan residue as an intrinsic fluorescent-probe. Biochim Biophys Acta 688(2):441–452PubMedGoogle Scholar
  56. Germain M, Balaguer P, Nicolas JC, Lopez F, Esteve JP, Sukhorukov GB, Winterhalter M, Richard-Foy H, Fournier D (2006) Protection of mammalian cell used in biosensors by coating with a polyelectrolyte shell. Biosens Bioelectron 21(8):1566–1573PubMedGoogle Scholar
  57. Giangaspero A, Sandri L, Tossi A (2001) Amphipathic alpha helical antimicrobial peptides—a systematic study of the effects of structural and physical properties on biological activity. Eur J Biochem 268(21):5589–5600PubMedGoogle Scholar
  58. Giusti F, Popot JL, 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 forster resonance energy transfer and dynamic surface tension measurements. Langmuir 28(28):10372–10380PubMedGoogle Scholar
  59. Goda T, Goto Y, Ishihara K (2010) Cell-penetrating macromolecules: direct penetration of amphipathic phospholipid polymers across plasma membrane of living cells. Biomaterials 31(8):2380–2387PubMedGoogle Scholar
  60. Guo ZJ, Kallus S, Akiyoshi K, Sunamoto J (1995) Artificial cell-wall for plant protoplast—coating of plasma-membrane with hydrophobized polysaccharides. Chem Lett 6:415–416Google Scholar
  61. Harris F, Dennison SR, Singh J, Phoenix DA (2013) On the selectivity and efficacy of defense peptides with respect to cancer cells. Med Res Rev 33(1):190–234PubMedGoogle Scholar
  62. He YC, Heine E, Keusgen N, Keul H, Moller M (2012) Synthesis and characterization of amphiphilic monodisperse compounds and poly(ethylene imine)s: influence of their microstructures on the antimicrobial properties. Biomacromolecules 13(3):612–623PubMedGoogle Scholar
  63. Hennig A, Gabriel GJ, Tew GN, Matile S (2008) Stimuli-responsive polyguanidino-oxanorbornene membrane transporters as multicomponent sensors in complex matrices. J Am Chem Soc 130(31):10338–10344PubMedPubMedCentralGoogle Scholar
  64. Henry SM, El-Sayed MEH, Pirie CM, Hoffman AS, Stayton PS (2006) pH-responsive poly(styrene-alt-maleic anhydride) alkylamide copolymers for intracellular drug delivery. Biomacromolecules 7(8):2407–2414PubMedGoogle Scholar
  65. Ho VHB, Slater NKH, Chen RJ (2011) pH-responsive endosomolytic pseudo-peptides for drug delivery to multicellular spheroids tumour models. Biomaterials 32(11):2953–2958PubMedGoogle Scholar
  66. Hoffman AS, Stayton PS, Press O, Murthy N, Lackey CA, Cheung C, Black F, Campbell J, Fausto N, Kyriakides TR, Bornstein P (2002) Design of “smart” polymers that can direct intracellular drug delivery. Polym Adv Technol 13(10–12):992–999Google Scholar
  67. Holowka EP, Sun VZ, Kamei DT, Deming TJ (2007) Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nat Mater 6(1):52–57PubMedGoogle Scholar
  68. Hong SP, Leroueil PR, Janus EK, Peters JL, Kober MM, Islam MT, Orr BG, Baker JR, Holl MMB (2006) Interaction of polycationic polymers with supported lipid bilayers and cells: nanoscale hole formation and enhanced membrane permeability. Bioconj Chem 17(3):728–734Google Scholar
  69. Hoskin DW, Ramamoorthy A (2008) Studies on anticancer activities of antimicrobial peptides. Biochim Biophy Acta Biomembr 1778(2):357–375Google Scholar
  70. Hu XL, Jing XB (2009) Biodegradable amphiphilic polymer-drug conjugate micelles. Expert Opin Drug Deliv 6(10):1079–1090PubMedGoogle Scholar
  71. Hu K, Schmidt NW, Zhu R, Jiang YJ, Lai GH, Wei G, Palermo EF, Kuroda K, Wong GCL, Yang LH (2013) A critical evaluation of random copolymer mimesis of homogeneous antimicrobial peptides. Macromolecules 46(5):1908–1915PubMedPubMedCentralGoogle Scholar
  72. Huin C, Gall TL, Barteau B, Pitard B, Montier T, Lehn P, Cheradame H, Guégan P (2011) Evidence of DNA transfer across a model membrane by a neutral amphiphilic block copolymer. J Gene Med 13:538–548PubMedGoogle Scholar
  73. Ishitsuka Y, Arnt L, Majewski J, Frey S, Ratajczek M, Kjaer K, Tew GN, Lee KYC (2006) Amphiphilic poly(phenyleneethynylene)s can mimic antimicrobial peptide membrane disordering effect by membrane insertion. J Am Chem Soc 128(40):13123–13129PubMedGoogle Scholar
  74. Ito M, Taguchi T (2009) Enhanced insulin secretion of physically crosslinked pancreatic beta-cells by using a poly(ethylene glycol) derivative with oleyl groups. Acta Biomater 5(8):2945–2952PubMedGoogle Scholar
  75. Iwasaki Y, Sakiyama M, Fujii S, Yusa S (2013) Surface modification of mammalian cells with stimuli-responsive polymers. Chem Commun 49(71):7824–7826Google Scholar
  76. Jiao CY, Delaroche D, Burlina F, Alves ID, Chassaing G, Sagan S (2009) Translocation and endocytosis for cell-penetrating peptide internalization. J Biol Chem 284(49):33957–33965PubMedPubMedCentralGoogle Scholar
  77. Khandelia H, Ipsen JH, Mouritsen OG (2008) The impact of peptides on lipid membranes. Biochim Biophys Acta Biomembr 1778(7–8):1528–1536Google Scholar
  78. Khormaee S, Choi Y, Shen MJ, Xu BY, Wu HT, Griffiths GL, Chen RJ, Slater NKH, Park JK (2013) Endosomolytic anionic polymer for the cytoplasmic delivery of sirnas in localized in vivo applications. Adv Funct Mater 23(5):565–574Google Scholar
  79. Kim JC, Kim JD (2002) Release property of temperature-sensitive liposome containing poly(N-isopropylacrylamide). Colloids Surfaces B 24(1):45–52Google Scholar
  80. Koren E, Torchilin VP (2012) Cell-penetrating peptides: breaking through to the other side. Trends Mol Med 18(7):385–393PubMedGoogle Scholar
  81. Krol S, del Guerra S, Grupillo M, Diaspro A, Gliozzi A, Marchetti P (2006) Multilayer nanoencapsulation. New approach for immune protection of human pancreatic islets. Nano Lett 6(9):1933–1939PubMedGoogle Scholar
  82. Kuroda K, Caputo GA, DeGrado WF (2009) The role of hydrophobicity in the antimicrobial and hemolytic activities of polymethacrylate derivatives. Chem Eur J 15(5):1123–1133PubMedGoogle Scholar
  83. Kusonwiriyawong C, van de Wetering P, Hubbell JA, Merkle HP, Walter E (2003) Evaluation of pH-dependent membrane-disruptive properties of poly(acrylic acid) derived polymers. Eur J Pharm Biopharm 56(2):237–246PubMedGoogle Scholar
  84. Lackey CA, Murthy N, Press OW, Tirrell DA, Hoffman AS, Stayton PS (1999) Hemolytic activity of pH-responsive polymer-streptavidin bioconjugates. Bioconj Chem 10(3):401–405Google Scholar
  85. Ladaviere C, Tribet C, Cribier S (2002) Lateral organization of lipid membranes induced by amphiphilic polymer inclusions. Langmuir 18(20):7320–7327Google Scholar
  86. Ladokhin AS, White SH (2001) ‘Detergent-like’ permeabilization of anionic lipid vesicles by melittin. Biochim Biophys Acta Biomembr 1514(2):253–260Google Scholar
  87. Last NB, Schlamadinger DE, Miranker AD (2013) A common landscape for membrane-active peptides. Protein Sci 22(7):870–882PubMedPubMedCentralGoogle Scholar
  88. le Maire M, Champeil P, Moller JV (2000) Interaction of membrane proteins and lipids with solubilizing detergents. Biochim Biophys Acta Biomembr 1508(1–2):86–111Google Scholar
  89. Lee HS, Park CB, Kim JM, Jang SA, Park IY, Kim MS, Cho JH, Kim SC (2008) Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide. Cancer Lett 271(1):47–55PubMedGoogle Scholar
  90. Liechty WB, Kryscio DR, Slaughter BV, Peppas NA (2010) Polymers for drug delivery systems. Annu Rev Chem Biomol Eng 1:149–173PubMedPubMedCentralGoogle Scholar
  91. Lienkamp K, Madkour A, Musante A, Nelson C, Nusslein K, Tew GN (2008) Antimicrobial polymers prepared by ROMP with unprecedented selectivity: a molecular construction kit approach. JACS 130:9836–9843Google Scholar
  92. Lienkamp K, Kumar KN, Som A, Nusslein K, Tew GN (2009) “Doubly selective” antimicrobial polymers: how do they differentiate between bacteria? Chem Eur J 15(43):11710–11714PubMedGoogle Scholar
  93. Madani F, Abdo R, Lindberg S, Hirose H, Futaki S, Langel U, Graslund A (2013) Modeling the endosomal escape of cell-penetrating peptides using a transmembrane pH gradient. Biochim Biophys Acta Biomembr 1828(4):1198–1204Google Scholar
  94. Magzoub M, Eriksson LEG, Graslund A (2002) Conformational states of the cell-penetrating peptide penetratin when interacting with phospholipid vesicles: effects of surface charge and peptide concentration. Biochim Biophys Acta Biomembr 1563(1–2):53–63Google Scholar
  95. Mansouri S, Merhi Y, Winnik FM, Tabrizian M (2011) Investigation of layer-by-layer assembly of polyelectrolytes on fully functional human red blood cells in suspension for attenuated immune response. Biomacromolecules 12(3):585–592PubMedGoogle Scholar
  96. Matile S, Jentzsch AV, Montenegro J, Fin A (2011) Recent synthetic transport systems. Chem Soc Rev 40(5):2453–2474PubMedGoogle Scholar
  97. Matsuda M, Ueno M, Endo Y, Inoue M, Sasaki M, Taguchi T (2012) Enhanced tissue penetration-induced high bonding strength of a novel tissue adhesive composed of cholesteryl group-modified gelatin and disuccinimidyl tartarate. Colloids Surfaces B 91:48–56Google Scholar
  98. Matsuzaki K, Murase O, Miyajima K (1995) kinetics of pore formation by an antimicrobial peptide, magainin-2 in phospholipid-bilayers. Biochemistry 34(39):12553–12559PubMedGoogle Scholar
  99. Mattheis C, Zhang Y, Agarwal S (2012) Thermo-switchable antibacterial activity. Macromol Biosci 12(10):1401–1412PubMedGoogle Scholar
  100. Mattheis C, Wang H, Meister C, Agarwal S (2013) Effect of guanidinylation on the properties of poly(2-aminoethylmethacrylate)-based antibacterial materials. Macromol Biosci 13(2):242–255PubMedGoogle Scholar
  101. Meng XT, Xing RG, Liu S, Yu HH, Li KC, Qin YK, Li PC (2012) Molecular weight and pH effects of aminoethyl modified chitosan on antibacterial activity in vitro. Int J Biol Macromol 50(4):918–924PubMedGoogle Scholar
  102. Milletti F (2012) Cell-penetrating peptides: classes, origin, and current landscape. Drug Discovery Today 17(15–16):850–860PubMedGoogle Scholar
  103. Mitchell DJ, Kim DT, Steinman L, Fathman CG, Rothbard JB (2000) Polyarginine enters cells more efficiently than other polycationic homopolymers. J Pept Res 56(5):318–325PubMedGoogle Scholar
  104. Miura S, Teramura Y, Iwata H (2006) Encapsulation of islets with ultra-thin polyion complex membrane through poly(ethylene glycol)-phospholipids anchored to cell membrane. Biomaterials 27(34):5828–5835PubMedGoogle Scholar
  105. Mollay C, Kreil G (1973) Fluorometric measurements on interaction of melittin with lecithin. Biochim Biophys Acta 316(2):196–203PubMedGoogle Scholar
  106. Mollay C, Kreil G, Berger H (1976) Action of phospholipases on cytoplasmic membrane of Escherichia coli—stimulation by melittin. Biochim Biophys Acta 426(2):317–324PubMedGoogle Scholar
  107. Munoz-Bonilla A, Fernandez-Garcia M (2012) Polymeric materials with antimicrobial activity. Prog Polym Sci 37(2):281–339Google Scholar
  108. Nakase I, Akita H, Kogure K, Graslund A, Langel U, Harashima H, Futaki S (2012a) Efficient intracellular delivery of nucleic acid pharmaceuticals using cell-penetrating peptides. Acc Chem Res 45(7):1132–1139PubMedGoogle Scholar
  109. Nakase I, Konishi Y, Ueda M, Saji H, Futaki S (2012b) Accumulation of arginine-rich cell-penetrating peptides in tumors and the potential for anticancer drug delivery in vivo. J Controll Release 159(2):181–188Google Scholar
  110. Nakase I, Okumura S, Katayama S, Hirose H, Pujals S, Yamaguchi H, Arakawa S, Shimizu S, Futaki S (2012c) Transformation of an antimicrobial peptide into a plasma membrane-permeable, mitochondria-targeted peptide via the substitution of lysine with arginine. Chem Commun 48(90):11097–11099Google Scholar
  111. Neu B, Voigt A, Mitlohner R, Leporatti S, Gao CY, Donath E, Kiesewetter H, Mohwald H, Meiselman HJ, Baumler H (2001) Biological cells as templates for hollow microcapsules. J Microencapsul 18(3):385–395PubMedGoogle Scholar
  112. Nguyen LT, Haney EF, Vogel HJ (2011) The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29(9):464–472PubMedGoogle Scholar
  113. Nicolas J, Mura S, Brambilla D, Mackiewicz N, Couvreur P (2013) Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chem Soc Rev 42(3):1147–1235PubMedGoogle Scholar
  114. Nochi T, Yuki Y, Takahashi H, Sawada S, Mejima M, Kohda T, Harada N, Kong IG, Sato A, Kataoka N, Tokuhara D, Kurokawa S, Takahashi Y, Tsukada H, Kozaki S, Akiyoshi K, Kiyono H (2010) Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines. Nat Mater 9(7):572–578PubMedGoogle Scholar
  115. Oda Y, Kanaoka S, Sato T, Aoshima S, Kuroda K (2011) Block versus random amphiphilic copolymers as antibacterial agents. Biomacromolecules 12(10):3581–3591PubMedGoogle Scholar
  116. Pack DW, Hoffman AS, Pun S, Stayton PS (2005) Design and development of polymers for gene delivery. Nat Rev Drug Discov 4(7):581–593PubMedGoogle Scholar
  117. Palermo EF, Kuroda K (2009) Chemical structure of cationic groups in amphiphilic polymethacrylates modulates the antimicrobial and hemolytic activities. Biomacromolecules 10(6):1416–1428PubMedGoogle Scholar
  118. Palermo EF, Sovadinova I, Kuroda K (2009) Structural determinants of antimicrobial activity and biocompatibility in membrane-disrupting methacrylamide random copolymers. Biomacromolecules 10(11):3098–3107PubMedGoogle Scholar
  119. Palermo EF, Lee DK, Ramamoorthy A, Kuroda K (2011) Role of cationic group structure in membrane binding and disruption by amphiphilic copolymers. J Phys Chem B 115(2):366–375PubMedGoogle Scholar
  120. Palermo EF, Vemparala S, Kuroda K (2012) Cationic spacer arm design strategy for control of antimicrobial activity and conformation of amphiphilic methacrylate random copolymers. Biomacromolecules 13(5):1632–1641PubMedGoogle Scholar
  121. Papo N, Shai Y (2003) Exploring peptide membrane interaction using surface plasmon resonance: differentiation between pore formation versus membrane disruption by lytic peptides. Biochemistry 42(2):458–466PubMedGoogle Scholar
  122. Papo N, Seger D, Makovitzki A, Kalchenko V, Eshhar Z, Degani H, Shai Y (2006) Inhibition of tumor growth and elimination of multiple metastases in human prostate and breast xenografts by systemic inoculation of a host defense-like lytic peptide. Cancer Res 66(10):5371–5378PubMedGoogle Scholar
  123. Pashkovskaya AA, Lukashev EP, Antonov PE, Finogenova OA, Ermakov YA, Melik-Nubarov NS, Antonenko YN (2006) Grafting of polylysine with polyethylenoxide prevents demixing of O-pyromellitylgramicidin in lipid membranes. Biochim Biophys Acta 1758:1685–1695PubMedGoogle Scholar
  124. Paslay LC, Abel BA, Brown TD, Koul V, Choudhary V, McCormick CL, Morgan SE (2012) Antimicrobial poly(methacrylamide) derivatives prepared via aqueous RAFT polymerization exhibit biocidal efficiency dependent upon cation structure. Biomacromolecules 13(8):2472–2482PubMedGoogle Scholar
  125. Paulmann M, Arnold T, Linke D, Oezdirekcan S, Kopp A, Gutsmann T, Kalbacher H, Wanke I, Schuenemann VJ, Habeck M, Buerck J, Ulrich AS, Schittek B (2012) Structure-activity analysis of the dermcidin-derived peptide DCD-1L, an anionic antimicrobial peptide present in human sweat. J Biol Chem 287(11):8434–8443PubMedPubMedCentralGoogle Scholar
  126. Persson D, Thoren PEG, Lincoln P, Norden B (2004) Vesicle membrane interactions of penetratin analogues. Biochemistry 43(34):11045–11055PubMedGoogle Scholar
  127. Poon GMK, Gariepy J (2007) Cell-surface proteoglycans as molecular portals for cationic peptide and polymer entry into cells. Biochem Soc Trans 35:788–793PubMedGoogle Scholar
  128. Popot JL, Althoff T, Bagnard D, Baneres JL, Bazzacco P, Billon-Denis E, Catoire LJ, Champeil P, Charvolin D, Cocco MJ, Cremel G, Dahmane T, de la Maza LM, Ebel C, Gabel F, Giusti F, Gohon Y, Goormaghtigh E, Guittet E, Kleinschmidt JH, Kuhlbrandt W, Le Bon C, Martinez KL, Picard M, Pucci B, Sachs JN, Tribet C, van Heijenoort C, Wien F, Zito F, Zoonens M (2011) Amphipols from a to z. Annu Rev Biophys 40(40):379–408PubMedGoogle Scholar
  129. Pourmousa M, Karttunen M (2013) Early stages of interactions of cell-penetrating peptide penetratin with a DPPC bilayer. Chem Phys Lipids 169:85–94PubMedGoogle Scholar
  130. Rao Z, Sasaki M, Taguchi T (2013) Development of amphiphilic, enzymatically-degradable PEG-peptide conjugate as cell crosslinker for spheroid formation. Colloids Surfaces B 101:223–227Google Scholar
  131. Relogio P, Bathfield M, Haftek-Terreau Z, Beija M, Favier A, Giraud-Panis MJ, D’Agosto F, Mandrand B, Farinha JPS, Charreyre MT, Martinho JMG (2013) Biotin-end-functionalized highly fluorescent water-soluble polymers. Polym Chem 4(10):2968–2981Google Scholar
  132. Riedl S, Zweytick D, Lohner K (2011) Membrane-active host defense peptides—challenges and perspectives for the development of novel anticancer drugs. Chem Phys Lipids 164(8):766–781PubMedPubMedCentralGoogle Scholar
  133. Ringsdorf H, Sackmann E, Simon J, Winnik FM (1993) Interactions of liposomes and hydrophobically-modified poly-(N-isopropylacrylamides)—an attempt to model the cytoskeleton. Biochim Biophys Acta 1153(2):335–344PubMedGoogle Scholar
  134. Rothbard JB, Garlington S, Lin Q, Kirschberg T, Kreider E, McGrane PL, Wender PA, Khavari PA (2000) Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nat Med 6(11):1253–1257PubMedGoogle Scholar
  135. Rothbard JB, Jessop TC, Lewis RS, Murray BA, Wender PA (2004) Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells. J Am Chem Soc 126(31):9506–9507PubMedGoogle Scholar
  136. Rothbard JB, Jessop TC, Wender PA (2005) Adaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cells. Adv Drug Deliv Rev 57(4):495–504PubMedGoogle Scholar
  137. Roux E, Lafleur M, Lataste E, Moreau P, Leroux JC (2003) On the characterization of pH-sensitive liposome/polymer complexes. Biomacromolecules 4(2):240–248PubMedGoogle Scholar
  138. Schulz M, Olubummo A, Binder WH (2012) Beyond the lipid-bilayer: interaction of polymers and nanoparticles with membranes. Soft Matter 8(18):4849–4864Google Scholar
  139. Scott MD, Murad KL, Koumpouras F, Talbot M, Eaton JW (1997) Chemical camouflage of antigenic determinants: stealth erythrocytes. Proc Natl Acad Sci USA 94(14):7566–7571PubMedGoogle Scholar
  140. Sebai S, Cribier S, Karimi A, Massotte D, Tribet C (2010) Permeabilization of lipid membranes and cells by a light-responsive copolymer. Langmuir 26(17):14135–14141PubMedGoogle Scholar
  141. Sebai SC, Milioni D, Walrant A, Alves ID, Sagan S, Huin C, Auvray L, Massotte D, Cribier S, Tribet C (2012) Photocontrol of the translocation of molecules, peptides, and quantum dots through cell and lipid membranes doped with azobenzene copolymers. Angew Chem Int Edn 51(9):2132–2136Google Scholar
  142. Shokeen M, Pressly ED, Hagooly A, Zheleznyak A, Ramos N, Fiamengo AL, Welch MJ, Hawker CJ, Anderson CJ (2011) Evaluation of multivalent, functional polymeric nanoparticles for imaging applications. ACS Nano 5(2):738–747PubMedPubMedCentralGoogle Scholar
  143. Siedenbiedel F, Tiller JC (2012) Antimicrobial polymers in solution and on surfaces: overview and functional principles. Polymers 4(1):46–71Google Scholar
  144. Som A, Reuter A, Tew GN (2012) Protein transduction domain mimics: the role of aromatic functionality. Angew Chem Int Edn 51(4):980–983Google Scholar
  145. Sovadinova I, Palermo EF, Huang R, Thoma LM, Kuroda K (2011a) Mechanism of polymer-induced hemolysis: nanosized pore formation and osmotic lysis. Biomacromolecules 12(1):260–268PubMedGoogle Scholar
  146. Sovadinova I, Palermo EF, Urban M, Mpiga P, Caputo GA, Kuroda K (2011b) Activity and mechanism of antimicrobial peptide-mimetic amphiphilic polymethacrylate derivatives. Polymers 3(3):1512–1532Google Scholar
  147. Stratton TR, Applegate BM, Youngblood JP (2011) Effect of steric hindrance on the properties of antibacterial and biocompatible copolymers. Biomacromolecules 12(1):50–56PubMedGoogle Scholar
  148. Suzuki T, Futaki S, Niwa M, Tanaka S, Ueda K, Sugiura Y (2002) Possible existence of common internalization mechanisms among arginine-rich peptides. J Biol Chem 277(4):2437–2443PubMedGoogle Scholar
  149. Swiston AJ, Cheng C, Um SH, Irvine DJ, Cohen RE, Rubner MF (2008) Surface functionalization of living cells with multilayer patches. Nano Lett 8(12):4446–4453PubMedGoogle Scholar
  150. Swiston AJ, Gilbert JB, Irvine DJ, Cohen RE, Rubner MF (2010) Freely suspended cellular “backpacks” lead to cell aggregate self-assembly. Biomacromolecules 11(7):1826–1832PubMedPubMedCentralGoogle Scholar
  151. Teramura Y, Iwata H (2010) Cell surface modification with polymers for biomedical studies. Soft Matter 6(6):1081–1091Google Scholar
  152. Teramura Y, Kaneda Y, Iwata H (2007) Islet-encapsulation in ultra-thin layer-by-layer membranes of poly(vinyl alcohol) anchored to poly(ethylene glycol)-lipids in the cell membrane. Biomaterials 28(32):4818–4825PubMedGoogle Scholar
  153. Teramura Y, Kaneda Y, Totani T, Iwata H (2008) Behavior of synthetic polymers immobilized on a cell membrane. Biomaterials 29(10):1345–1355PubMedGoogle Scholar
  154. Teramura Y, Oommen OP, Olerud J, Hilborn J, Nilsson B (2013) Microencapsulation of cells, including islets, within stable ultra-thin membranes of maleimide-conjugated PEG-lipid with multifunctional crosslinkers. Biomaterials 34(11):2683–2693PubMedGoogle Scholar
  155. Tezgel AO, Telfer JC, Tew GN (2011) De Novo designed protein transduction domain mimics from simple synthetic polymers. Biomacromolecules 12(8):3078–3083PubMedGoogle Scholar
  156. Thomas JL, Borden KA, Tirrell DA (1996) Modulation of mobilities of fluorescent membrane probes by adsorption of a hydrophobic polyelectrolyte. Macromolecules 29(7):2570–2576Google Scholar
  157. Torchilin VP (2012) Multifunctional nanocarriers. Adv Drug Deliv Rev 64:302–315Google Scholar
  158. Totani T, Teramura Y, Iwata H (2008) Immobilization of urokinase on the islet surface by amphiphilic poly(vinyl alcohol) that carries alkyl side chains. Biomaterials 29(19):2878–2883PubMedGoogle Scholar
  159. Travkova OG, Andra J, Mohwald H, Brezesinski G (2013) Influence of Arenicin on Phase Transitions and Ordering of Lipids in 2D Model Membranes. Langmuir 29(39):12203–12211PubMedGoogle Scholar
  160. Tribet C, Vial F (2008) Flexible macromolecules attached to lipid bilayers: impact on fluidity, curvature, permeability and stability of the membranes. Soft Matter 4(1):68–81Google Scholar
  161. Tsogas I, Sideratou Z, Tsiourvas D, Theodossiou TA, Paleos CM (2007) Interactive transport of guanidinylated poly(propylene imine)-based dendrimers through liposomal and cellular membranes. ChemBioChem 8(15):1865–1876PubMedGoogle Scholar
  162. Ukawa M, Akita H, Masuda T, Hayashi Y, Konno T, Ishihara K, Harashima H (2010) 2-Methacryloyloxyethyl phosphorylcholine polymer (MPC)-coating improves the transfection activity of GALA-modified lipid nanoparticles by assisting the cellular uptake and intracellular dissociation of plasmid DNA in primary hepatocytes. Biomaterials 31(24):6355–6362PubMedGoogle Scholar
  163. Unger T, Oren Z, Shai Y (2001) The effect of cyclization of magainin 2 and melittin analogues on structure, function, and model membrane interactions: implication to their mode of action. Biochemistry 40(21):6388–6397PubMedGoogle Scholar
  164. Veerabadran NG, Goli PL, Stewart-Clark SS, Lvov YM, Mills DK (2007) Nanoencapsulation of stem cells within polyelectrolyte multilayer shells. Macromol Biosci 7(7):877–882PubMedGoogle Scholar
  165. 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(3):853–862PubMedGoogle Scholar
  166. 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(1):75–78Google Scholar
  167. 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(13):7506–7513PubMedGoogle Scholar
  168. Vives E, Brodin P, Lebleu B (1997) A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J Biol Chem 272(25):16010–16017PubMedGoogle Scholar
  169. Vogel H, Jahnig F (1986) The structure of melittin in membranes. Biophys J 50(4):573–582PubMedPubMedCentralGoogle Scholar
  170. Walrant A, Correia I, Jiao C-Y, Lequin O, Bent EH, Goasdoue N, Lacombe C, Chassaing G, Sagan S, Alves ID (2011) Different membrane behaviour and cellular uptake of three basic arginine-rich peptides. Biochim Biophys Acta Biomembr 1808(1):382–393Google Scholar
  171. Walrant A, Vogel A, Correia I, Lequin O, Olausson BES, Desbat B, Sagan S, Alves ID (2012) Membrane interactions of two arginine-rich peptides with different cell internalization capacities. Biochim Biophys Acta Biomembr 1818(7):1755–1763Google Scholar
  172. Weerakkody D, Moshnikova A, Thakur MS, Moshnikova V, Daniels J, Engelman DM, Andreev OA, Reshetnyak YK (2013) Family of pH (low) insertion peptides for tumor targeting. Proc Natl Acad Sci USA 110(15):5834–5839PubMedGoogle Scholar
  173. Werner M, Sommer JU, Baulin VA (2012) Homo-polymers with balanced hydrophobicity translocate through lipid bilayers and enhance local solvent permeability. Soft Matter 8(46):11714–11722Google Scholar
  174. Wieprecht T, Beyermann M, Seelig J (1999) Binding of antibacterial magainin peptides to electrically neutral membranes: thermodynamics and structure. Biochemistry 38(32):10377–10387PubMedGoogle Scholar
  175. Wilson JT, Cui WX, Kozovskaya V, Kharlampieva E, Pan D, Qu Z, Krishnamurthy VR, Mets J, Kumar V, Wen J, Song YH, Tsukruk VV, Chaikof EL (2011) Cell surface engineering with polyelectrolyte multilayer thin films. J Am Chem Soc 133(18):7054–7064PubMedGoogle Scholar
  176. Wimley WC (2010) Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5(10):905–917PubMedPubMedCentralGoogle Scholar
  177. Yang Z, Sahay G, Sriadibhatla S, Kabanov AV (2008) Amphiphilic block copolymers enhance cellular uptake and nuclear entry of polyplex-delivered DNA. Bioconj Chem 19(10):1987–1994Google Scholar
  178. Yaroslavov AA, Melik-Nubarov NS, Menger FM (2006) Polymer-induced flip–flop in biomembranes. Acc Chem Res 39(10):702–710PubMedGoogle Scholar
  179. Ye J, Fox SA, Cudic M, Rezler EM, Lauer JL, Fields GB, Terentis AC (2010) Determination of penetratin secondary structure in live cells with raman microscopy. J Am Chem Soc 132(3):980–988PubMedPubMedCentralGoogle Scholar
  180. Yessine MA, Leroux JC (2004) Membrane-destabilizing polyanions: interaction with lipid bilayers and endosomal escape of biomacromolecules. Adv Drug Deliv Rev 56(7):999–1021PubMedGoogle Scholar
  181. Yessine MA, Dufresne MH, Meier C, Petereit HU, Leroux JC (2007) Proton-actuated membrane-destabilizing polyion complex micelles. Bioconj Chem 18(3):1010–1014Google Scholar
  182. Yook S, Jeong JH, Jung YS, Hong SW, Im BH, Seo JW, Park JB, Lee M, Ahn CH, Lee H, Lee DY, Byun Y (2012) Molecularly engineered islet cell clusters for diabetes mellitus treatment. Cell Transpl 21(8):1775–1789Google Scholar
  183. Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415(6870):389–395PubMedGoogle Scholar
  184. Zhang SW, Nelson A, Coldrick Z, Chen RJ (2011) The effects of substituent grafting on the interaction of pH-responsive polymers with phospholipid monolayers. Langmuir 27(13):8530–8539PubMedGoogle Scholar
  185. Ziegler A, Blatter XL, Seelig A, Seelig J (2003) Protein transduction domains of HIV-1 and SIV TAT interact with charged lipid vesicles. Binding mechanism and thermodynamic analysis. Biochemistry 42(30):9185–9194PubMedGoogle Scholar
  186. Zorko M, Langel U (2005) Cell-penetrating peptides: mechanism and kinetics of cargo delivery. Adv Drug Deliv Rev 57(4):529–545PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Département de ChimieEcole Normale Supérieure, UMR 8640 CNRS-ENS-UPMCParisFrance
  2. 2.Département de ChimieSorbonne Universités - UPMC University Paris 06, École Normale Supérieure-PSL University, CNRS, LBMParisFrance

Personalised recommendations