Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution

Alves, Isabel D.; Goasdoué, N.; Correia, Isabelle; Aubry, S.; Galanth, Cécile; Sagan, Sandrine; Lavielle, Solange; Chassaing, Gérard

doi:10.1016/j.bbagen.2008.04.004

Cited by 115 publications

(101 citation statements)

References 64 publications

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“…Indeed, this time-limited phenomenon implies that the cell-penetrating peptide had to recruit and use up specific membrane components, likely phospholipids or glycosphingolipids, to translocate with them into cells. These results support previous works on model membrane or in cells that already suggested that a limited and specific lipid/peptide import in cells (14,30,31).…”

Section: Discussionsupporting

confidence: 82%

Translocation and Endocytosis for Cell-penetrating Peptide Internalization

Jiao¹,

Delaroche

Burlina

et al. 2009

Journal of Biological Chemistry

291

284

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Cell-penetrating peptides (CPPs) share the property of cellular internalization. The question of how these peptides reach the cytoplasm of cells is still widely debated. Herein, we have used a mass spectrometry-based method that enables quantification of internalized and membrane-bound peptides. Internalization of the most used CPP was studied at 37°C (endocytosis and translocation) and 4°C (translocation) in wild type and proteoglycandeficient Chinese hamster ovary cells. Both translocation and endocytosis are internalization pathways used by CPP. The choice of one pathway versus the other depends on the peptide sequence (not the number of positive changes), the extracellular peptide concentration, and the membrane components. There is no relationship between the high affinity of these peptides for the cell membrane and their internalization efficacy. Translocation occurs at low extracellular peptide concentration, whereas endocytosis, a saturable and cooperative phenomenon, is activated at higher concentrations. Translocation operates in a narrow time window, which implies a specific lipid/peptide co-import in cells.Cell-penetrating peptides (CPPs) 3 that share the activity of cellular entry are usually short peptides of less than 20 amino acids highly enriched in basic residues. Among them, Antp, Tat-(48 -60), and oligoarginine peptides are the most intensively studied. Despite the wide use of these CPPs as macromolecular delivery devices, the internalization mechanism of these peptides in cells still remains largely controversial. The energy dependence of the internalization mechanism is unique because all endocytotic pathways are inhibited at low temperature. Consequently, at low temperature, internalization likely reflects a direct translocation mechanism. Early studies proposed that Antp enters cells by an energy-independent membrane translocation mechanism (1). This first analysis was then contradicted by other studies that suggested, with the use of inhibitors, the involvement of endocytosis in the cellular internalization of cell-penetrating peptides (2-4).The hypothesis that endocytosis was the only internalization mechanism of CPP resulted from studies examining whether the temperature or the binding to cell-surface glycosaminoglycans (GAGs) were critical for peptide internalization. Most of these interpretations resulted from fluorescence microscopy data. For instance, it was reported that Antp, Tat, and oligoarginine peptides were not efficiently internalized in the Chinese hamster ovary (CHO) mutant pgsA-745 cell line, which does not produce cell-surface heparan sulfate or chondroitin sulfate (5, 6). However, recent data indicates that Tat-mediated transduction occurs in the absence of heparan sulfate and chondroitin sulfate (7). The discrepancies observed between studies may be explained in part by different incubation conditions (peptide/cells ratio and peptide concentration) (8), limits in fluorescence imaging, such as quenching (9), or fluorophore-dependent intracellular trafficking (10), as...

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Section: Discussionsupporting

confidence: 82%

Translocation and Endocytosis for Cell-penetrating Peptide Internalization

Jiao¹,

Delaroche

Burlina

et al. 2009

Journal of Biological Chemistry

291

284

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“…Interestingly, in the bacterial inhibition assay, penetratin showed a stronger inhibition of E. coli than of S. aureus, indicating a mode of action against E. coli other than simple membrane disruption. The MIC values were within the range of earlier findings for penetratin (14,(35)(36)(37).…”

Section: Discussionsupporting

confidence: 60%

Cell-Penetrating Antimicrobial Peptides – Prospectives for Targeting Intracellular Infections

et al. 2015

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“…[36] Other biophysical studies confirmed differential interaction of amphipathic AMPs with zwitterionic versus anionic lipids. [37] Using deep-UV Raman spectroscopy Cooley and co-workers provided the first evidence of lipid-dependent secondary structure (helix) formation and aggregation of ME1 peptide in the presence of micelles. [38] Recently, Torrent et al observed interdependencies between aggregation-promoting, amyloid-like properties and antimicrobial activity, with positively charged residues playing a function-determining feature of AMPs.…”

mentioning

confidence: 99%

Piloting the Membranolytic Activities of Peptides with a Self‐organizing Map

Lin¹,

Hiss²,

Schneider³

et al. 2014

ChemBioChem

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Antimicrobial peptides (AMPs) show remarkable selectivity toward lipid membranes and possess promising antibiotic potential. Their modes of action are diverse and not fully understood, and innovative peptide design strategies are needed to generate AMPs with improved properties. We present a de novo peptide design approach that resulted in new AMPs possessing low-nanomolar membranolytic activities. Thermal analysis revealed an entropy-driven mechanism of action. The study demonstrates sustained potential of advanced computational methods for designing peptides with the desired activity.

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Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution

Cited by 115 publications

References 64 publications

Translocation and Endocytosis for Cell-penetrating Peptide Internalization

Translocation and Endocytosis for Cell-penetrating Peptide Internalization

Cell-Penetrating Antimicrobial Peptides – Prospectives for Targeting Intracellular Infections

Piloting the Membranolytic Activities of Peptides with a Self‐organizing Map

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