Interactions of KLA Amphipathic Model Peptides with Lipid Monolayers

Erbe, Andreas; Kerth, Andreas; Dathe, Margitta; Blume, Alfred

doi:10.1002/cbic.200900444

Cited by 21 publications

(22 citation statements)

References 33 publications

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“…The electrostatically driven preferential interaction of our peptides with negatively charged lipid mono- and bilayers has been shown in earlier studies 25,27,30. The subsequent interaction via hydrophobic residues in the peptides with the lipid bilayer triggers the formation of lipid protrusions that bulged out of the SLBs as seen by time-lapse fluorescence microscopy.…”

Section: Discussionsupporting

confidence: 70%

Morphological Changes Induced by the Action of Antimicrobial Peptides on Supported Lipid Bilayers

et al. 2010

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We utilized epifluorescence microscopy to investigate the morphological changes in labelled lipid bilayers supported on quartz surfaces (SLBs) induced by the interaction of cationic antimicrobial peptides with the lipid membranes. The SLBs were prepared from POPG, POPC, POPE and mixtures thereof as well as from E. coli lipid extract. We succeeded in the preparation of POPG and POPG-rich SLBs without the necessity to use fusogenic agents like calcium by using the Langmuir Blodgett/Langmuir Schaefer transfer method. The adsorption of the peptides to the SLBs was initially driven by electrostatic interactions with the PG headgroups, and led to the formation of lipid protrusions bulging out from the lipid layer facing the bulk, originating particularly from domain boundaries and membrane defects. The shape, size and frequency of the lipid protrusions are mainly controlled by the peptide macroscopic properties and the membrane composition. A restructuring of the lipid protrusions into other structures can also occur over time.

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Section: Discussionsupporting

confidence: 70%

Morphological Changes Induced by the Action of Antimicrobial Peptides on Supported Lipid Bilayers

et al. 2010

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“…For KLAL, the peptide helix was found to be tilted in the POPG monolayer with an angle of >60°w ith respect to the surface normal. 22 We believe that the orientation of KLA1 in POPG monolayers is similar to that of KLAL, since the two peptides differ only in one amino acid.…”

Section: ' Results and Discussionmentioning

confidence: 97%

The Binding of an Amphipathic Peptide to Lipid Monolayers at the Air/Water Interface Is Modulated by the Lipid Headgroup Structure

Arouri

Kerth

Dathe³

et al. 2011

Langmuir

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We used monolayer techniques combined with infrared reflection absorption spectroscopy (IRRAS) to study the behavior of the 18-mer cationic peptide KLA1 (KLAL KLAL KAW KAAL KLA-NH2) at the air/water interface as well as its interaction with lipid films of different composition. The adsorption of the peptide from the subphase to the air/water interface was observed measuring the increase in surface pressure (π) at constant surface area. The binding of the peptide to lipid monolayers was followed by recording the change in lipid area at a constant surface pressure (π = 30 mN m(-1)). At the air/water interface, the peptide initially adopted an α-helix at large surface area per molecule, that is, low surface pressure, but further accumulation of the peptide at the interface induced a conformational change from α-helix to intermolecular β-sheet, driven by intermolecular aggregation. When the peptide was injected into the subphase underneath lipid monolayers, it adsorbed pronouncedly to anionic monolayers containing phosphatidylglycerol forming an α-helix, but not to zwitterionic lipid monolayers. The large change in area observed upon peptide binding suggests that the peptide helix was incorporated into the apolar chain region of the lipids. An apparent partition coefficient of (0.3-1) × 10(6) M(-1) could be calculated for binding to pure POPG monolayers. Significant differences in binding affinity were observed comparing PG/PC with PG/PE monolayers, with the latter showing a higher binding constant. This shows that not only electrostatic and hydrophobic effects but also specific interactions between the headgroups of the lipids and the peptide side chains modulate the binding affinity.

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“…PN159 was described as a TJ modulator and permeability-enhancing peptide on airway epithelial cell layers in vitro and in vivo [4], and in our previous comparative work we found it also very effective on culture models of the blood–brain and intestinal barriers [8]. The same peptide, known also as KLAL or MAP was extensively studied for its cell membrane action as a CPP [10,11,12,35]. However, the identity of the differently named molecule was not previously known for the researchers of the two fields.…”

Section: Discussionmentioning

confidence: 99%

Dual Action of the PN159/KLAL/MAP Peptide: Increase of Drug Penetration across Caco-2 Intestinal Barrier Model by Modulation of Tight Junctions and Plasma Membrane Permeability

et al. 2019

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The absorption of drugs is limited by the epithelial barriers of the gastrointestinal tract. One of the strategies to improve drug delivery is the modulation of barrier function by the targeted opening of epithelial tight junctions. In our previous study the 18-mer amphiphilic PN159 peptide was found to be an effective tight junction modulator on intestinal epithelial and blood–brain barrier models. PN159, also known as KLAL or MAP, was described to interact with biological membranes as a cell-penetrating peptide. In the present work we demonstrated that the PN159 peptide as a penetration enhancer has a dual action on intestinal epithelial cells. The peptide safely and reversibly enhanced the permeability of Caco-2 monolayers by opening the intercellular junctions. The penetration of dextran molecules with different size and four efflux pump substrate drugs was increased several folds. We identified claudin-4 and -7 junctional proteins by docking studies as potential binding partners and targets of PN159 in the opening of the paracellular pathway. In addition to the tight junction modulator action, the peptide showed cell membrane permeabilizing and antimicrobial effects. This dual action is not general for cell-penetrating peptides (CPPs), since the other three CPPs tested did not show barrier opening effects.

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Interactions of KLA Amphipathic Model Peptides with Lipid Monolayers

Cited by 21 publications

References 33 publications

Morphological Changes Induced by the Action of Antimicrobial Peptides on Supported Lipid Bilayers

Morphological Changes Induced by the Action of Antimicrobial Peptides on Supported Lipid Bilayers

The Binding of an Amphipathic Peptide to Lipid Monolayers at the Air/Water Interface Is Modulated by the Lipid Headgroup Structure

Dual Action of the PN159/KLAL/MAP Peptide: Increase of Drug Penetration across Caco-2 Intestinal Barrier Model by Modulation of Tight Junctions and Plasma Membrane Permeability

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