Skip to main content
SpringerLink
Log in

Membrane Crossover by Cell-Penetrating Peptides: Kinetics and Mechanisms – From Model to Cell Membrane Perturbation by Permeant Peptides

  • Chapter
  • First Online:
Intracellular Delivery

Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 5))

Abstract

Membrane-active peptides are a large family endowed with a wide pattern of biological activities (antimicrobial, viral fusion and infection, cell-penetrating or protein-transduction domain), which share the property of interacting with membranes and being internalized in eukaryotic cells. Apart from pinocytosis internalization pathways, these peptides have the capacity to re-organize lipid membranes and to lead to membrane fusion, disruption or pore formation. In this chapter, we focus on these membrane perturbation processes evoked by cell-penetrating peptides that have been widely studied with membrane models and in cultured cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AMP:

Antimicrobial Peptide

Antp:

antennapedia, homeoprotein

CHO:

chinese hamster ovary cells

CPP:

Cell-Penetrating Peptide

CS:

Chondroitin Sulphate

DOPC:

dioleoylphosphatidylcholine

DOPG:

dioleoylphosphatidylglycerol

DPPC:

dipalmitoyl phosphatidylcholine

DSC:

Differential Scanning Calorimetry

ESR:

Electron Spin Resonance spectroscopy

GUV:

Giant Unilamellar Vesicle

HS:

Heparan Sulphate

HSPG:

Heparan Sulphate ProteoGlycans

ITC:

Isothermal Titration Calorimetry

LUV:

Large Unilamellar Vesicle

MAP:

Membrane Active Peptide

NBD:

Nitrobenzo-2-oxa-1,3-diazole

NMR:

Nuclear Magnetic Resonance Spectroscopy

PEP-1:

hepatite C virus related peptide, SGSWLRDVWDWICTVLTDFK-TWLQSKLDYKD-NH2

P/L ratio:

peptide over lipid ratio

Transportan:

galanin/mastoparan chimeric peptide, GWTLNSAGYLLGKINLK-ALAALAKKIL-NH2

Tat:

Trans Activator of Transcription protein

Tat(46–58):

Tat derived peptide, GRKKRRQRRRPQ-NH2

References

  • Afonin S, Frey A, Bayerl S, Fischer D, Wadhwani P, Weinkauf S, Ulrich AS (2006) The cell-penetrating peptide TAT(48–60) induces a non-lamellar phase in DMPC membranes. Chemphyschem 7:2134–2142.

    PubMed  CAS  Google Scholar 

  • Alves ID, Goasdoué N, Correia I, Aubry S, Galanth C, Sagan, S, Lavielle S, Chassaing G (2008) Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution. Biochim Biophys Acta. 1780:948–59.

    PubMed  CAS  Google Scholar 

  • Alves ID, Correia I, Jiao CY, Sachon E, Sagan S, Lavielle S, Tollin G, Chassaing G. (2009) The interaction of cell-penetrating peptides with lipid model systems and subsequent lipid reorganization: thermodynamic and structural characterization. J Pept Sci 15:200–209.

    PubMed  CAS  Google Scholar 

  • Alves ID, Jiao CY, Aubry S, Aussedat B, Burlina F, Chassaing G, Sagan S (2010) Cell biology meets biophysics to unveil the different mechanisms of penetratin internalization in cells. Biochim Biophys Acta. 2010 Feb 10. [Epub ahead of print]

    Google Scholar 

  • Amand HL, Fant K, Nordén B, Esbjörner EK (2008) Stimulated endocytosis in penetratin uptake: effect of arginine and lysine. Biochem Biophys Res Commun. 2008 Jul 11;371(4):621–5. Epub 2008 May 13

    PubMed  Google Scholar 

  • Aussedat B, Dupont E, Sagan S, Joliot A, Lavielle S, Chassaing G, Burlina F (2008) Modifications in the chemical structure of Trojan carriers: impact on cargo delivery, Chem. Commun. 12:1398–1400.

    Google Scholar 

  • Berlose JP, Convert O, Derossi D, Brunissen A, Chassaing G (1996) Conformational and associative behaviours of the third helix of antennapedia homeodomain in membrane-mimetic environments. Eur J Biochem 242:372–386.

    PubMed  CAS  Google Scholar 

  • Binder H, Lindblom G (2003) Charge-dependent translocation of the Trojan peptide penetratin across lipid membranes. Biophys J 85:982–995.

    PubMed  CAS  Google Scholar 

  • Brunet I, Di Nardo AA, Sonnier L, Beurdeley M, Prochiantz A (2007) The topological role of homeoproteins in the developing central nervous system. Trends Neurosci 6:260–267.

    Google Scholar 

  • Caesar CE, Esbjörner EK, Lincoln P, Nordén B (2006) Membrane interactions of cell-penetrating peptides probed by tryptophan fluorescence and dichroism techniques: correlations of structure to cellular uptake. Biochemistry 45:7682–7692.

    PubMed  CAS  Google Scholar 

  • Cahill K (2010) Molecular electroporation and the transduction of oligoarginines. Phys Biol 7:1–14

    Google Scholar 

  • Cheung JC, Kim Chiaw P, Deber CM, Bear CE (2009) A novel method for monitoring the cytosolic delivery of peptide cargo. J Control Release. 2009 Jul 1;137(1):2–7.

    PubMed  CAS  Google Scholar 

  • 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 269:2918–2926.

    PubMed  CAS  Google Scholar 

  • Christiaens B, Grooten J, Reusens M, Joliot A, Goethals M, Vandekerckhove J, Prochiantz A, Rosseneu M (2004) Membrane interaction and cellular internalization of penetratin peptides. Eur. J. Biochem 271, 1187–1197.

    PubMed  CAS  Google Scholar 

  • Clayton AH, Atcliffe BW, Howlett GJ, Sawyer WH (2006) Conformation and orientation of penetratin in phospholipid membranes. J Pept Sci 12:233–238.

    PubMed  CAS  Google Scholar 

  • Curnow P, Mellor H, Stephens DJ, Lorch M, Booth PJ (2005) Translocation of the cell-­penetrating Tat peptide across artificial bilayers and into living cells. Biochem Soc Symp 72:199–209.

    PubMed  CAS  Google Scholar 

  • Dathe M, Schumann M, Wieprecht T, Winkler A, Beyermann M, Krause E, Matsuzaki K, Murase O, Bienert M (1996) Peptide helicity and membrane surface charge modulate the balance of electrostatic and hydrophobic interactions with lipid bilayers and biological membranes. Biochemistry 35:12612–12622.

    PubMed  CAS  Google Scholar 

  • Delaroche D, Aussedat B, Aubry S, Chassaing G, Burlina F, Clodic G, Bolbach G, Lavielle S, Sagan S (2007) Tracking a new cell-penetrating (W/R) nonapeptide, through an enzyme-stable mass spectrometry reporter tag. Anal Chem 79:1932–1938.

    PubMed  CAS  Google Scholar 

  • Derossi D, Joliot AH, Chassaing G, Prochiantz A (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 269:10444–50.

    PubMed  CAS  Google Scholar 

  • Derossi D, Calvet S, Trembleau A, Brunissen A, Chassaing G, Prochiantz A (1996) Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J Biol Chem 271 (1996) 18188–18193.

    PubMed  CAS  Google Scholar 

  • Deshayes S, Plenat T, Aldrian-Herrada G, Divita G, Le Grimellec C, Heitz F (2004) Primary amphipathic cell-penetrating peptides: structural requirements and interactions with model membranes. Biochemistry 43:7698–7706.

    PubMed  CAS  Google Scholar 

  • Deshayes S, Decaffmeyer M, Brasseur R, Thomas A (2008) Structural polymorphism of two CPP: an important parameter of activity. Biochim Biophys Acta 1778:1197–1205.

    Google Scholar 

  • Dietz GP, Bähr M (2004) Delivery of bioactive molecules into the cell: the Trojan horse approach. Mol Cell Neurosci. 2:85–131.

    Google Scholar 

  • Drin G, Cottin S, Blanc E, Rees AR, Temsamani J. (2003) Studies on the internalization mechanism of cationic cell-penetrating peptides. J Biol Chem 278:31192–31201.

    PubMed  CAS  Google Scholar 

  • Duchardt F, Ruttekolk IR, Verdurmen WP, Lortat-Jacob H, Bürck J, Hufnagel H, Fischer R, van den Heuvel M, Löwik DW, Vuister GW, Ulrich A, de Waard M, Brock R (2009) A cell-penetrating peptide derived from human lactoferrin with conformation-dependent uptake efficiency. J Biol Chem 284:36099–36108.

    PubMed  CAS  Google Scholar 

  • El-Andaloussi S, Jarver P, Johansson HJ, Langel U (2007) Cargo-dependent cytotoxicity and delivery efficacy of cell-penetrating peptides: a comparative study, Biochem J 407: 285–292.

    PubMed  CAS  Google Scholar 

  • Eiríksdóttir E, Mäger I, Lehto T, El Andaloussi S, Langel U. (2010a) Cellular internalization kinetics of (luciferin-)cell-penetrating peptide conjugates. Bioconjug Chem. 21:1662–1672.

    PubMed  Google Scholar 

  • Eiríksdóttir E, Konate K, Langel U, Divita G, Deshayes S (2010b) Secondary structure of cell-penetrating peptides controls membrane interaction and insertion. Biochim Biophys Acta. 1798:1119–1128.

    PubMed  Google Scholar 

  • El-Andaloussi S, Johansson HJ, Holm T, Langel U (2004) A novel cell-penetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids. Mol Ther 15:1820–1826.

    Google Scholar 

  • Epand RF, Schmitt MA, Gellman SH, Epand RM (2006) Role of membrane lipids in the mechanism of bacterial species selective toxicity by two alpha/beta-antimicrobial peptides. Biochim Biophys Acta. 1758:1343–50.

    PubMed  CAS  Google Scholar 

  • Epand RM, Epand RF (2009) Lipid domains in bacterial membranes and the action of antimicrobial agents, Biochim Biophys Acta 1788:289–294.

    PubMed  CAS  Google Scholar 

  • Fischer R, Waizenegger T, Kohler K, Brock R (2002) A quantitative validation of fluorophore-labelled cell-permeable peptide conjugates: fluorophore and cargo dependence of import. Biochim Biophys Acta 1564, 365–374.

    PubMed  CAS  Google Scholar 

  • Fuchs SM, Raines RT (2004) Pathway for polyarginine entry into mammalian cells. Biochemistry 43:2438–2444.

    PubMed  CAS  Google Scholar 

  • 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 276:5836–5840.

    PubMed  CAS  Google Scholar 

  • Ghibaudi E, Boscolo B, Inserra G, Laurenti E, Traversa S, Barbero L, Ferrari RP (2005) The interaction of the cell-penetrating peptide penetratin with heparin, heparansulfates and phospholipid vesicles investigated by ESR spectroscopy. J Pept Sci. 11:401–409.

    PubMed  CAS  Google Scholar 

  • Goncalves E, Kitas E, Seelig J (2005) Binding of oligoarginine to membrane lipids and heparan sulfate: structural and thermodynamic characterization of a cell-penetrating peptide. Biochemistry 44:2692–2702.

    PubMed  CAS  Google Scholar 

  • Glaser RW, Leikin SL, Chernomordik LV, Pastushenko VF, Sokirko AI (1988) Reversible electrical breakdown of lipid bilayers: formation and evolution of pores. Biochim Biophys Acta 940:275–87.

    PubMed  CAS  Google Scholar 

  • Hallbrink M, Floren A, Elmquist A, Pooga M, Bartfai T, Langel U (2001) Cargo delivery kinetics of cell-penetrating peptides, Biochim. Biophys. Acta 1515:101–109.

    PubMed  CAS  Google Scholar 

  • Hansen M, Kilk K, Langel U (2008) Predicting cell-penetrating peptides. Adv Drug Deliv Rev 60(4–5):572–579.

    PubMed  CAS  Google Scholar 

  • Henriques ST, Costa J, Castanho MA (2005) Translocation of beta-galactosidase mediated by the cell-penetrating peptide pep-1 into lipid vesicles and human HeLa cells is driven by membrane electrostatic potential. Biochemistry 44:10189–10198.

    PubMed  Google Scholar 

  • Henriques ST, Castanho MA, Pattenden LK, Aguilar MI (2010) Fast membrane association is a crucial factor in the peptide pep-1 translocation mechanism: a kinetic study followed by surface plasmon resonance. Biopolymers 94:314–322.

    PubMed  CAS  Google Scholar 

  • Herce HD, Garcia AE (2007) Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes. Proc Natl Acad Sci USA. 104:20805–10.

    PubMed  CAS  Google Scholar 

  • Herce HD, Garcia AE, Litt J, Kane RS, Martin P, Enrique N, Rebolledo A, Milesi V (2009) Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell penetrating peptides. Biophys J 97:1917–1925.

    PubMed  CAS  Google Scholar 

  • Hitz T, Iten R, Gardiner J, Namoto K, Walde P, Seebach D (2006) Interaction of alpha-and beta-oligoarginine-acids and amides with anionic lipid vesicles: a mechanistic and thermodynamic study. Biochemistry 45:5817–5829.

    PubMed  CAS  Google Scholar 

  • Ivanov AI (2008) Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? Methods Mol Biol 440:15–33.

    PubMed  CAS  Google Scholar 

  • Jiao CY, Delaroche D, Burlina F, Alves ID, Chassaing G, Sagan S (2009) Translocation and endocytosis for cell-penetrating peptide internalization. J Biol Chem 284:33957–33965.

    PubMed  CAS  Google Scholar 

  • Joanne P, Galanth C, Goasdoué N, Nicolas P, Sagan S, Lavielle S, Chassaing G, El Amri C, Alves ID (2009) Lipid reorganization induced by membrane-active peptides probed using differential scanning calorimetry. Biochim Biophys Acta 1788:1772–81.

    PubMed  CAS  Google Scholar 

  • Joliot A, Triller A, Volovitch M, Pernelle C, Prochiantz A (1991) alpha-2,8-Polysialic acid is the neuronal surface receptor of antennapedia homeobox peptide. New Biol 3:1121–1134.

    PubMed  CAS  Google Scholar 

  • Joliot A, Prochiantz A (2008) Homeoproteins as natural Penetratin cargoes with signaling properties. Adv Drug Deliv Rev 60: 608–613.

    PubMed  CAS  Google Scholar 

  • Jones SW, Christison R, Bundell K, Voyce CJ, Brockbank SM, Newham P, Lindsay MA (2005) Characterisation of cell-penetrating peptide-mediated peptide delivery. Br J Pharmacol, 145, 1093–1102.

    PubMed  CAS  Google Scholar 

  • Jones LR, Goun EA, Shinde R, Rothbard JB, Contag CH, Wender PA (2006) Releasable luciferin-transporter conjugates: tools for the real-time analysis of cellular uptake and release. J Am Chem Soc 128:6526–6527.

    PubMed  CAS  Google Scholar 

  • Jones AT (2007) J Cell Mol Med 11:670–684. Macropinocytosis: searching for an endocytic identity and role in the uptake of cell penetrating peptides.

    PubMed  CAS  Google Scholar 

  • Kichler A, Mason AJ, Bechinger B (2006) Cationic amphipathic histidine rich peptides for gene delivery. Biochim Biophys Acta 1758:301–307.

    PubMed  CAS  Google Scholar 

  • Lamaziere A, Burlina F, Wolf C, Chassaing G, Trugnan G and Ayala-Sanmartin J (2007) Non-metabolic membrane tubulation and permeability induced by bioactive peptides. PLoS ONE 2:e201.

    PubMed  Google Scholar 

  • Lee HL, Dubikovskaya EA, Hwang H, Semyonov AN, Wang H, Jones LR, Twieg RJ, Moerner WE, Wender PA. (2008) Single-molecule motions of oligoarginine transporter conjugates on the plasma membrane of Chinese hamster ovary cells. J Am Chem Soc. 130:9364–9370.

    PubMed  CAS  Google Scholar 

  • Le Roux I, Joliot AH, Bloch-Gallego E, Prochiantz A, Volovitch M (1993) Neurotrophic activity of the Antennapedia homeodomain depends on its specific DNA-binding properties. Proc Natl Acad Sci U S A. 90:9120–9124.

    PubMed  Google Scholar 

  • Letoha T, Gaál S, Somlai C, Czajlik A, Perczel A, Penke B (2003) Membrane translocation of penetratin and its derivatives in different cell lines. J Mol Recognit 16:272–279.

    PubMed  CAS  Google Scholar 

  • Lindberg M, Biverståhl H, Gräslund A, Mäler L (2003) Structure and positioning comparison of two variants of penetratin in two different membrane mimicking systems by NMR. Eur J Biochem 270:3055–3063.

    PubMed  CAS  Google Scholar 

  • Lindgren M, Hallbrink M, Prochiantz A, Langel U (2000) Cell-penetrating peptides. Trends Pharmcol Sci 21:99–103.

    CAS  Google Scholar 

  • Magzoub M, Kilk K, Eriksson LE, Langel U, Graslund A (2001) Interaction and structure induction of cell-penetrating peptides in the presence of phospholipid vesicles. Biochim Biophys Acta 1512:77–89.

    PubMed  CAS  Google Scholar 

  • Magzoub M, Eriksson LE, 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. Acta1563, 53–63.

    PubMed  CAS  Google Scholar 

  • Maiolo JR, Ferrer M, Ottinger EA (2005) Effects of cargo molecules on the cellular uptake of arginine-rich cell-penetrating peptides, Biochim Biophys Acta 1712: 161–172.

    PubMed  CAS  Google Scholar 

  • Manning GS, Bresler EH, Wendt RP (1969) Irreversible Thermodynamics and Flow across Membranes. Science 166:1438.

    PubMed  CAS  Google Scholar 

  • Mitchell DJ, Kim DT, Steinman L, Fathman CG, Rothbard JB (2000) Polyarginine enters cells more efficiently than other polycationic homopolymers, J. Pept. Res. 56:318–325.

    PubMed  CAS  Google Scholar 

  • Morris MC, Depollier J, Mery J, Heitz F, Divita G (2001) A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat. Biotechnol. 19:1173–1176.

    PubMed  CAS  Google Scholar 

  • Morris MC, Deshayes S, Heitz F, Divita G (2008) Cell-penetrating peptides: from molecular mechanisms to therapeutics. Biol Cell 100:201–217.

    PubMed  CAS  Google Scholar 

  • Mueller J, Kretzschmar I, Volkmer R, Boisguerin P (2008) Bioconjug Chem 19:2363–2374. Comparison of cellular uptake using 22 CPPs in 4 different cell lines.

    PubMed  CAS  Google Scholar 

  • Nakase I, Niwa M, Takeuchi T, Sonomura K, Kawabata N, Koike Y, Takehashi M, Tanaka S, Ueda K, Simpson JC, Jones AT, Sugiura Y, Futaki S (2004) Cellular uptake of arginine-rich peptides: Roles for macropinocytosis and actin rearrangement. Mol Ther 10:1011–1022.

    PubMed  CAS  Google Scholar 

  • Nakase I, Tadokoro A, Kawabata N, Takeuchi T, Katoh H, Hiramoto K, Negishi M, Nomizu M, Sugiura Y, Futaki S (2007) Interaction of arginine-rich peptides with membrane-associated proteoglycans is crucial for induction of actin organization and macropinocytosis Biochemistry 46:492–501.

    PubMed  CAS  Google Scholar 

  • Nakase I, Takeuchi T, Tanaka G, Futaki S (2008) Methodological and cellular aspects that govern the internalization mechanisms of arginine-rich cell-penetrating peptides. Adv Drug Deliv Rev 60:598–607.

    PubMed  CAS  Google Scholar 

  • Nishihara M, Perret F, Takeuchi T, Futaki S, Lazar AN, Coleman AW, Sakai N, Matile S (2005) Arginine magic with new counterions up the sleeve. Org Biomol Chem. 3:1659–1669.

    PubMed  CAS  Google Scholar 

  • Palm-Apergi C, Lorents A, Padari K, Pooga M, Hällbrink M (2009) The membrane repair response masks membrane disturbances caused by cell-penetrating peptide uptake. FASEB J. 23:214–223.

    PubMed  CAS  Google Scholar 

  • Polyansky A A, Volynsky PE, Arseniev AS, Efremov RG (2009) Adaptation of a membrane-active peptide to heterogeneous environment. I. Structural plasticity of the peptide. J Phys Chem B 113:1107–1119.

    PubMed  CAS  Google Scholar 

  • Pooga M, Hallbrink M, Zorko M, Langel U (1998) Cell penetration by transportan. FASEB J 12:67–77.

    Google Scholar 

  • Prochiantz A (2008) Protein and peptide transduction, twenty years later a happy birthday. Adv Drug Deliv Rev. 2008 Mar 1;60(4–5):448–51.

    PubMed  CAS  Google Scholar 

  • Prochiantz A, Joliot A. (2003) Can transcription factors function as cell-cell signalling molecules? Nat Rev Mol Cell Biol 10:814–819.

    Google Scholar 

  • Pujals S, Fernández-Carneado J, López-Iglesias C, Kogan MJ, Giralt E (2006) Mechanistic aspects of CPP-mediated intracellular drug delivery: relevance of CPP self-assembly. Biochim Biophys Acta. 1758:264–279.

    PubMed  CAS  Google Scholar 

  • Ram N, Aroui S, Jaumain E, Bichraoui H, Mabrouk K, Ronjat M, Lortat-Jacob H, De Waard M (2008) Direct peptide interaction with surface glycosaminoglycans contributes to the cell penetration of maurocalcine. J Biol Chem 283:24274–24284.

    PubMed  CAS  Google Scholar 

  • Richard JP, Melikov K, Vives E, Ramos C, Verbeure B, Gait MJ, Chernomordik LV, Lebleu B (2003) Cell-penetrating Peptides – A reevaluation of the mechanism of uptake. J Biol Chem 278:585–590.

    PubMed  CAS  Google Scholar 

  • 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 126:9506–9507.

    PubMed  CAS  Google Scholar 

  • 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 57:495– 504.

    PubMed  CAS  Google Scholar 

  • Roux M, Neumann JM, Bloom M, Devaux PF (1988) 2 H and 31P NMR study of pentalysine interaction with headgroup deuterated phosphatidylcholine and phosphatidylserine. Eur Biophys J 16:267–273.

    PubMed  CAS  Google Scholar 

  • Roux M, Neumann JM, Hodges RS, Devaux PF, Bloom M (1989) Conformational changes of phospholipid headgroups induced by a cationic integral membrane peptide as seen by deuterium magnetic resonance. Biochemistry 28:2313–2321.

    PubMed  CAS  Google Scholar 

  • Sakai N, Matile S (2003) Anion-mediated transfer of polyarginine across liquid and bilayer membranes. J Am Chem Soc 125:14348–14356.

    PubMed  CAS  Google Scholar 

  • Salamon Z, Lindblom G, Tollin G (2003) Plasmon-waveguide resonance and impedance spectroscopy studies of the interaction between penetratin and supported lipid bilayer membranes. Biophys J 84:1796–1807.

    PubMed  CAS  Google Scholar 

  • Sawant R, Torchilin V (2010) Intracellular transduction using cell-penetrating peptides. Mol Biosyst 6:628–640.

    PubMed  CAS  Google Scholar 

  • Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta. 1462:55–70.

    PubMed  CAS  Google Scholar 

  • Siegel DP (1993) Energetics of intermediates in membrane fusion: comparison of stalk and inverted micellar intermediate mechanisms. Biophysical Journal 65:2124–2140.

    PubMed  CAS  Google Scholar 

  • Su Y, Mani R, Doherty T, Waring AJ, Hong M (2008) Reversible sheet-turn conformational change of a cell-penetrating peptide in lipid bilayers studied by solid-state NMR J Mol Biol 381:1133–1144.

    PubMed  CAS  Google Scholar 

  • Takeuchi T, Kosuge M, Tadokoro A, Sugiura Y, Nishi M, Kawata M, Sakai N, Matile S, Futaki S (2006) Direct and rapid cytosolic delivery using cell-penetrating peptides mediated by pyrenebutyrate ACS Chem Biol. 1:299–303.

    PubMed  CAS  Google Scholar 

  • Tassetto M, Maizel A, Osorio J, Joliot A (2005) Plant and animal homeodomains use convergent mechanisms for intercellular transfer, EMBO Rep 6:885–890.

    PubMed  CAS  Google Scholar 

  • Ter-Avetisyan G, Tünnemann G, Nowak D, Nitschke M, Herrmann A, Drab M, Cardoso MC (2009) Cell entry of arginine-rich peptides is independent of endocytosis. J Biol Chem 284:3370–3378.

    Google Scholar 

  • Terrone D, Sang SL, Roudaia L, Silvius JR (2003) Penetratin and related cell-penetrating cationic peptides can translocate across lipid bilayers in the presence of a transbilayer potential. Biochemistry 42:13787–13799.

    PubMed  CAS  Google Scholar 

  • Thoren PE, Persson D, Karlsson M, Norden B (2000) The antennapedia peptide penetratin translocates across lipid bilayers — the first direct observation. FEBS Lett 482:265–268.

    PubMed  CAS  Google Scholar 

  • Thoren PE, Persson D, Lincoln P, Norden B (2005) Membrane destabilizing properties of cell-penetrating peptides. Biophys. Chem. 114:169–179.

    PubMed  CAS  Google Scholar 

  • Tiriveedhi V, Butko P (2007) A fluorescence spectroscopy study on the interactions of the TAT-PTD peptide with model lipid membranes. Biochemistry 46: 3888–3895.

    PubMed  CAS  Google Scholar 

  • Verdurmen WPR, Thanos M, Ruttekolk IR, Gulbins E, Brock R (2010) Cationic cell-penetrating peptides induce ceramide formation via acid sphingomyelinase: Implications for uptake. J Control Release 147:171–179.

    PubMed  CAS  Google Scholar 

  • Vives E, Brodin P, Lebleu BA (1997) truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J Biol Chem 272:16010–16017.

    PubMed  CAS  Google Scholar 

  • Wadia JS, Stan RV, Dowdy SF (2004) Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med 10:310–315.

    PubMed  CAS  Google Scholar 

  • Walter C, Ott I, Gust R, Neundorf I (2009) Specific Labeling With Potent Radiolabels Alters the Uptake of Cell-Penetrating Peptides. Biopolymers 92:445–451.

    Google Scholar 

  • Wender PA, Mitchell DJ, Pattabiraman K, Pelkey ET, Steinman L, Rothbard JB (2001) The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters. Proc Nat Acad Sci 97:13003–13008.

    Google Scholar 

  • Wender PA, Galliher WC, Goun EA, Jones LR, Pillow TH (2008) The design of guanidinium-rich transporters and their internalization mechanisms. Adv Drug Deliv Rev 60:452–72.

    PubMed  CAS  Google Scholar 

  • Weeks BS, Lieberman DM, Johnson B, Roque E, Green M, Loewenstein P, Oldfield EH, Kleinman HK (1995) Neurotoxicity of the human-immunodeficiency-virus type-1 TAT transactivator to PC12 cells requires the Tat amino-acid-49-58 basic domain. J Neurosci Res 42:34–40.

    PubMed  CAS  Google Scholar 

  • Wieprecht T, Beyermann M, Seelig J (2002) Thermodynamics of the coil alpha-helix transition of amphipathic peptides in a membrane environment: the role of vesicle curvature. Biophys Chem 96:191–201.

    PubMed  CAS  Google Scholar 

  • 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 132:980–988.

    PubMed  CAS  Google Scholar 

  • Yesylevskyy S, Marrink SJ, Mark AE (2009) Alternative mechanisms for the interaction of the cell-penetrating peptides penetratin and the TAT peptide with lipid bilayers. Biophys J. 97:40–9.

    PubMed  CAS  Google Scholar 

  • Ziegler A, Seelig J (2004) Interaction of the protein transduction domain of HIV-1 TAT with heparan sulfate: binding mechanism and thermodynamic parameters. Biophys J. 86:254–63.

    PubMed  CAS  Google Scholar 

  • Zimm BH, Le Bret M (1983) Counter-ion condensation and system dimensionality. J Biomol Struct Dyn 1:461–471.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Biomolecule, Universite Pierre et Marie Curie, Paris Cedex 05, 75252, France

    Isabel D. Alves, Nicolas Rodriguez, Sophie Cribier & Sandrine Sagan

Authors
  1. Isabel D. Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolas Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophie Cribier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandrine Sagan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandrine Sagan .

Editor information

Editors and Affiliations

  1. , Chemical and Biological Engineering, Vanderbilt University, VU Station B 351604, Nashville, 37235, Tennessee, USA

    Aleš Prokop

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Alves, I.D., Rodriguez, N., Cribier, S., Sagan, S. (2011). Membrane Crossover by Cell-Penetrating Peptides: Kinetics and Mechanisms – From Model to Cell Membrane Perturbation by Permeant Peptides. In: Prokop, A. (eds) Intracellular Delivery. Fundamental Biomedical Technologies, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1248-5_7

Download citation

Publish with us

Policies and ethics

Search

Navigation