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Mechanisms of peptide-induced pore formation in lipid bilayers investigated by oriented 31P solid-state NMR spectroscopy.

Bertelsen K, Dorosz J, Hansen SK, Nielsen NC, Vosegaard T - PLoS ONE (2012)

Bottom Line: For two AMPs, alamethicin and novicidin, we observe that the majority of the lipids remain in a planar bilayer conformation but that a number of lipids are involved in the peptide anchoring.These lipids display reduced dynamics.Our study supports previous studies showing that alamethicin adopts a transmembrane arrangement without significant disturbance of the surrounding lipids, while novicidin forms toroidal pores at high concentrations leading to more extensive membrane disturbance.

View Article: PubMed Central - PubMed

Affiliation: Center for Insoluble Protein Structures (inSPIN), Department of Chemistry, University of Aarhus, Aarhus, Denmark.

ABSTRACT
There is a considerable interest in understanding the function of antimicrobial peptides (AMPs), but the details of their mode of action is not fully understood. This motivates extensive efforts in determining structural and mechanistic parameters for AMP's interaction with lipid membranes. In this study we show that oriented-sample (31)P solid-state NMR spectroscopy can be used to probe the membrane perturbations and disruption by AMPs. For two AMPs, alamethicin and novicidin, we observe that the majority of the lipids remain in a planar bilayer conformation but that a number of lipids are involved in the peptide anchoring. These lipids display reduced dynamics. Our study supports previous studies showing that alamethicin adopts a transmembrane arrangement without significant disturbance of the surrounding lipids, while novicidin forms toroidal pores at high concentrations leading to more extensive membrane disturbance.

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Sketches of the geometries (left column) and examples of membrane/AMP systems described by the geometries (right column).The geometries are referred to a thinned bilayer (a) and toroidal pore (b) [65] and are identical to those proposed by Wi and Kim [28]. See text for further description of the parameters.
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pone-0047745-g002: Sketches of the geometries (left column) and examples of membrane/AMP systems described by the geometries (right column).The geometries are referred to a thinned bilayer (a) and toroidal pore (b) [65] and are identical to those proposed by Wi and Kim [28]. See text for further description of the parameters.

Mentions: Since antimicrobial peptides interact with lipid bilayers and induce defects which alter the geometry of the bilayer, it appears rational to supplement observations of chemical shielding parameters for specific spins (e.g., 15N) in the peptides with 31P solid-state NMR data for the lipids in which the peptides are embedded to detect the equally probable alternation (defects) of the membranes in proximity of the lipid phosphate headgroups. In this study, the perturbation of the membranes by AMPs is investigated by orienting the bilayers mechanically between glass plates with the bilayer normal parallel to the external magnetic field. Figure 2 shows models/schemes of two simple membrane geometries, which one could expect to occur in a perturbed bilayer. A thinned bilayer may be modeled as shown in Figure 2a, while a toroidal pore may be modeled by the geometry in Figure 2b. Later, we will see that the barrel-stave model, in which the peptides penetrate the bilayer without significant perturbation of the bilayer are best modeled by a thinned bilayer with a reduced diffusion rate.


Mechanisms of peptide-induced pore formation in lipid bilayers investigated by oriented 31P solid-state NMR spectroscopy.

Bertelsen K, Dorosz J, Hansen SK, Nielsen NC, Vosegaard T - PLoS ONE (2012)

Sketches of the geometries (left column) and examples of membrane/AMP systems described by the geometries (right column).The geometries are referred to a thinned bilayer (a) and toroidal pore (b) [65] and are identical to those proposed by Wi and Kim [28]. See text for further description of the parameters.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475706&req=5

pone-0047745-g002: Sketches of the geometries (left column) and examples of membrane/AMP systems described by the geometries (right column).The geometries are referred to a thinned bilayer (a) and toroidal pore (b) [65] and are identical to those proposed by Wi and Kim [28]. See text for further description of the parameters.
Mentions: Since antimicrobial peptides interact with lipid bilayers and induce defects which alter the geometry of the bilayer, it appears rational to supplement observations of chemical shielding parameters for specific spins (e.g., 15N) in the peptides with 31P solid-state NMR data for the lipids in which the peptides are embedded to detect the equally probable alternation (defects) of the membranes in proximity of the lipid phosphate headgroups. In this study, the perturbation of the membranes by AMPs is investigated by orienting the bilayers mechanically between glass plates with the bilayer normal parallel to the external magnetic field. Figure 2 shows models/schemes of two simple membrane geometries, which one could expect to occur in a perturbed bilayer. A thinned bilayer may be modeled as shown in Figure 2a, while a toroidal pore may be modeled by the geometry in Figure 2b. Later, we will see that the barrel-stave model, in which the peptides penetrate the bilayer without significant perturbation of the bilayer are best modeled by a thinned bilayer with a reduced diffusion rate.

Bottom Line: For two AMPs, alamethicin and novicidin, we observe that the majority of the lipids remain in a planar bilayer conformation but that a number of lipids are involved in the peptide anchoring.These lipids display reduced dynamics.Our study supports previous studies showing that alamethicin adopts a transmembrane arrangement without significant disturbance of the surrounding lipids, while novicidin forms toroidal pores at high concentrations leading to more extensive membrane disturbance.

View Article: PubMed Central - PubMed

Affiliation: Center for Insoluble Protein Structures (inSPIN), Department of Chemistry, University of Aarhus, Aarhus, Denmark.

ABSTRACT
There is a considerable interest in understanding the function of antimicrobial peptides (AMPs), but the details of their mode of action is not fully understood. This motivates extensive efforts in determining structural and mechanistic parameters for AMP's interaction with lipid membranes. In this study we show that oriented-sample (31)P solid-state NMR spectroscopy can be used to probe the membrane perturbations and disruption by AMPs. For two AMPs, alamethicin and novicidin, we observe that the majority of the lipids remain in a planar bilayer conformation but that a number of lipids are involved in the peptide anchoring. These lipids display reduced dynamics. Our study supports previous studies showing that alamethicin adopts a transmembrane arrangement without significant disturbance of the surrounding lipids, while novicidin forms toroidal pores at high concentrations leading to more extensive membrane disturbance.

Show MeSH