Dataset Information

Real-time measurement of membrane conformational states induced by antimicrobial peptides: balance between recovery and lysis.

ABSTRACT: The disruption of membranes by antimicrobial peptides is a multi-state process involving significant structural changes in the phospholipid bilayer. However, direct measurement of these membrane structural changes is lacking. We used a combination of dual polarisation interferometry (DPI), surface plasmon resonance spectroscopy (SPR) and atomic force microscopy (AFM) to measure the real-time changes in membrane structure through the measurement of birefringence during the binding of magainin 2 (Mag2) and a highly potent analogue in which Ser(8), Gly(13) and Gly(18) has been replaced with alanine (Mag-A). We show that the membrane bilayer undergoes a series of structural changes upon peptide binding before a critical threshold concentration is reached which triggers a significant membrane disturbance. We also propose a detailed model for antimicrobial peptide action as a function of the degree of bilayer disruption to provide an unprecedented in-depth understanding of the membrane lysis in terms of the interconversion of different membrane conformational states in which there is a balance between recovery and lysis.

SUBMITTER: Hall K

PROVIDER: S-EPMC4073255 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Real-time measurement of membrane conformational states induced by antimicrobial peptides: balance between recovery and lysis.

Hall Kristopher K Lee Tzong-Hsien TH Mechler Adam I AI Swann Marcus J MJ Aguilar Marie-Isabel MI

Scientific reports 20140627

The disruption of membranes by antimicrobial peptides is a multi-state process involving significant structural changes in the phospholipid bilayer. However, direct measurement of these membrane structural changes is lacking. We used a combination of dual polarisation interferometry (DPI), surface plasmon resonance spectroscopy (SPR) and atomic force microscopy (AFM) to measure the real-time changes in membrane structure through the measurement of birefringence during the binding of magainin 2 ( ...[more]

PMID: 24969959

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Project description:Antimicrobial activity of many AMPs can be improved by lysine-to-arginine substitution due to a more favourable interaction of arginine guanidinium moiety with bacterial membranes. In a previous work, the structural and functional characterization of an amphipathic antimicrobial peptide named RiLK1, including lysine and arginine as the positively charged amino acids in its sequence, was reported. Specifically, RiLK1 retained its β-sheet structure under a wide range of environmental conditions (temperature, pH, and ionic strength), and exhibited bactericidal activity against Gram-positive and Gram-negative bacteria and fungal pathogens with no evidence of toxicity on mammalian cells. To further elucidate the influence of a lysine-to-arginine replacement on RiLK1 conformational properties, antimicrobial activity and peptide-liposome interaction, a new RiLK1-derivative, named RiLK3, in which the lysine is replaced with an arginine residue, was projected and characterised in comparison with its parental compound. The results evidenced that lysine-to-arginine mutation not only did not assure an improvement in the antimicrobial potency of RiLK1 in terms of bactericidal, virucidal and fungicidal activities, but rather it was completely abolished against the hepatitis A virus. Therefore, RiLK1 exhibited a wide range of antimicrobial activity like other cationic peptides, although the exact mechanisms of action are not completely understood. Moreover, tryptophan fluorescence measurements confirmed that RiLK3 bound to negatively charged lipid vesicles with an affinity lower than that of RiLK1, although no substantial differences from the structural and self-assembled point of view were evidenced. Therefore, our findings imply that antimicrobial efficacy and selectivity are affected by several complex and interrelated factors related to substitution of lysine with arginine, such as their relative proportion and position. In this context, this study could provide a better rationalisation for the optimization of antimicrobial peptide sequences, paving the way for the development of novel AMPs with broad applications.

Dataset Information

Real-time measurement of membrane conformational states induced by antimicrobial peptides: balance between recovery and lysis.

Publications

Real-time measurement of membrane conformational states induced by antimicrobial peptides: balance between recovery and lysis.

Similar Datasets

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