How lipids influence the mode of action of membrane-active peptides

Sevcsik, Eva; Pabst, Georg; Jilek, Alexander; Lohner, Karl

doi:10.1016/j.bbamem.2007.06.015

Cited by 95 publications

(112 citation statements)

References 50 publications

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“…In parallel, the enthalpy (ΔH) decreased, which is typical for systems including very small structures, such as disc-like micelles. These findings are similar to those observed in interdigitation models with small AMPs and apolipoproteins (Gursky, 2002;Sevcsik et al, 2007Sevcsik et al, , 2008. Further, rh-Epocontaining liposomal suspensions were measured with DLS to identify discoid subpopulation.…”

Section: Resultssupporting

confidence: 79%

“…Disc-like micelles appeared as rice grain-shaped structures with a diameter of about 30 nm ( Figure 1B). This appearance is typical for discoid structures, because they are mainly adsorbed at their hydrophobic edges onto the copper grid (Gursky, 2002;Jayaraman et al, 2005;Mehta et al, 2003;Sevcsik et al, 2007Sevcsik et al, , 2008. Though rh-Epo containing vesicles were described as drug-delivery systems before, our observations showed, for the first time, that rh-Epo enables the transformation of liposomal membranes (Maitani et al, 1996(Maitani et al, , 1999Moriya et al, 1997).…”

Section: Resultssupporting

confidence: 52%

“…In the case of anionic EPG, it is indicated that the topological transformation by rh-Epo is thermodynamically driven and initiated by protein association. Previously, severe membrane remodeling was demonstrated for small antimicrobial peptides (AMPs), lysozyme, apolipoproteins, toxins, and surfactants (Gursky, 2002;Jayaraman et al, 2005;Kuboi et al, 2000;Mehta et al, 2003;Sevcsik et al, 2007Sevcsik et al, , 2008Zschörnig et al, 2005). Additionally, tumor necrosis factor and interleukin-1 alpha were reported to disintegrate liposomal membranes (Oku et al, 1987(Oku et al, , 1995.…”

Section: Resultsmentioning

confidence: 99%

“…However, the electrostatic attraction alone cannot explain the formation of discoid structures, because simple adsorption is insufficient to interrupt membrane structures, as reported for interleukin-2 and interferon-gamma (Koppenhagen et al, 1998b;Van Slooten et al, 2001;Kuboi et al, 2000;Nomura et al, 2001;Sevcsik et al, 2007Sevcsik et al, , 2008Takiguchi et al, 2002). Thus, the effect of the protein structure was examined by applying DTT-treated rh-Epo to EPG-ULVs.…”

Section: Resultsmentioning

confidence: 99%

“…The transformation of liposomes is reported for molecules such as lysozyme and apolipoproteins, small AMPs, toxins, and surfactants leading to lipid structures different-to round-shaped vesicles (Gursky, 2002;Jayaraman et al, 2005;Kuboi et al, 2000;Mehta et al, 2003;Sevcsik et al, 2007Sevcsik et al, , 2008Zschörnig et al, 2005). Even cytokines such as interleukin-1 alpha and tumor necrosis factor are described as membrane-destabilizing proteins inducing leakage in liposomes (Oku et al, 1987(Oku et al, , 1995.…”

Section: Resultsmentioning

confidence: 99%

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Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Strobach¹,

Kunert²,

Stadlmann³

et al. 2009

Journal of Liposome Research

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Recombinant human erythropoietin (rh-Epo) is well accepted as a hematopoietic drug, but many other pleiotropic properties are currently under investigation. Rh-Epo-induced receptor-mediated signal transductions are accompanied with membrane dynamic processes, which facilitate the activation of individual pathways. However, its direct effect on membrane dynamics is still unknown. In the present study, we have proven the capability of rh-Epo to associate to and transform artificial lipid membranes. Association studies using neutral, negatively, and positively charged liposomes with the native as well as modified rh-Epo were performed and analyzed by transmission electron microscopy and differential scanning calorimetry. By these studies, we demonstrated that rh-Epo has the capability to transform negatively charged unilamellar vesicles into so-called disc-like micelles. Rh-Epo association to the negatively charged head groups via lysine and arginine initiates this transformation. At physiological temperatures, conformational changes within the rh-Epo structure expose a defined amino-acid sequence, which is able to induce the formation of discoid membrane structures. Enzymatic digestion, analysis, and isolation of related peptides by rp-HPLC and characterization by MS/MS enabled the identification of the membrane-affecting domain of rh-Epo (MAD-E) that represents the exposed helix B of rh-Epo. Finally, association studies performed with these peptides confirmed that the MAD-E is responsible for the formation of disc-like micelles. Since this helix B of rh-Epo has recently been supposed to be involved in the activation of neuroprotective pathways, we believe that the membrane-transforming capacity of rh-Epo participates in the proliferative activity of rh-Epo.

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Section: Resultssupporting

confidence: 79%

Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Strobach¹,

Kunert²,

Stadlmann³

et al. 2009

Journal of Liposome Research

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Structural characterization of phosphatidylglycerol model membranes containing the antibiotic target lipid II molecule: a Raman microspectroscopy study

Morales

Alvarez

2016

J. Raman Spectrosc.

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Effects induced by the incorporation of lipid II (LII) molecule into phosphatidylglycerol (PG) membranes were studied by Raman microspectroscopy. Spectral behavior of multilayer vesicles in liquid crystalline and gel phases formed by pure PG lipids and by PG/LII mixtures was evaluated. Differences shown by specific spectral markers of the lipid structure were associated with perturbations on the bilayer as response to the LII incorporation. Identification and interpretation of bands assigned to vibrations belonging to groups of the lipid polar region were supported by computational predictions. Quantum‐chemical calculations – B3LYP/6‐311++G(d,p) – were performed for a model charged molecule that mimics the PG lipid moiety in solvated state. Our Raman spectra demonstrate that the lipid phase is a determinant factor for both the bactoprenol tail penetration into the hydrophobic bilayer region and the perturbation degree at the membrane surface by the peptidoglycan moiety, because differential effects were observed for the two lipid systems studied. LII was able to penetrate the hydrophobic region of the lipid bilayer in the fluid phase, reaching the deep core and causing significant alterations in both the carbohydrate chain and the headgroup regions. By contrast, penetration of LII into a bilayer in the gel estate was restricted because of the high lipid packing that characterizes this phase. In this last case, interactions at the membrane surface were also indicative of partial interdigitating effect. Findings presented here provide valuable experimental evidence that contributes to the understanding of the mechanism by which lantibiotics recognize bacterial membranes. Copyright © 2016 John Wiley & Sons, Ltd.

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Different mechanisms of action of antimicrobial peptides: insights from fluorescence spectroscopy experiments and molecular dynamics simulations

Bocchinfuso

Palleschi

Orioni

et al. 2009

Journal of Peptide Science

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Most antimicrobial peptides exert their activity by interacting with bacterial membranes, thus perturbing their permeability. They are investigated as a possible solution to the insurgence of bacteria resistant to the presently available antibiotic drugs. However, several different models have been proposed for their mechanism of membrane perturbation, and the molecular details of this process are still debated. Here, we compare fluorescence spectroscopy experiments and molecular dynamics (MD) simulations regarding the association with lipid bilayers and lipid perturbation for two different amphiphilic helical antimicrobial peptides, PMAP-23 and trichogin GA IV. PMAP-23, a cationic peptide member of the cathelicidin family, is considered to induce membrane permeability according to the Shai-Matsuzaki-Huang ''carpet'' model, while trichogin GA IV is a neutral peptide, member of the peptaibol family. Although several lines of evidence suggest a ''barrel-stave'' mechanism of pore formation for the latter peptide, its length is only half the normal thickness of a lipid bilayer. Both fluorescence spectroscopy experiments and MD simulations indicated that PMAP-23 associates with membranes close to their surface and parallel to it, and in this arrangement it causes a severe perturbation to the bilayer, both regarding its surface tension and lipid order. By contrast, trichogin GA IV can undergo a transition from a surface-bound state to a transmembrane orientation. In the first arrangement, it does not cause any strong membrane perturbation, while in the second orientation it might be able to span the bilayer from one side to the other, despite its relatively short length, by causing a significant thinning of the membrane.

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How lipids influence the mode of action of membrane-active peptides

Cited by 95 publications

References 50 publications

Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Structural characterization of phosphatidylglycerol model membranes containing the antibiotic target lipid II molecule: a Raman microspectroscopy study

Different mechanisms of action of antimicrobial peptides: insights from fluorescence spectroscopy experiments and molecular dynamics simulations

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