248 research outputs found
Defect formation of lytic peptides in lipid membranes and their influence on the thermodynamic properties of the pore environment
We present an experimental study of the pore formation processes of small
amphipathic peptides in model phosphocholine lipid membranes. We used atomic
force microscopy to characterize the spatial organization and structure of
alamethicin- and melittin- induced defects in lipid bilayer membranes and the
influence of the peptide on local membrane properties. Alamethicin induced
holes in gel DPPC membranes were directly visualized at different peptide
concentrations. We found that the thermodynamic state of lipids in gel
membranes can be influenced by the presence of alamethicin such that nanoscopic
domains of fluid lipids form close to the peptide pores, and that the elastic
constants of the membrane are altered in their vicinity. Melittin-induced holes
were visualized in DPPC and DLPC membranes at room temperature in order to
study the influence of the membrane state on the peptide induced hole
formation. Also differential scanning calorimetry was used to investigate the
effect of alamethicin on the lipid membrane phase behavior.Comment: 11 pages, 7 figures, 1 tabl
The inositol 1,4,5-trisphosphate-gated Ca2+ channel: effect of the protein thiol reagent thimerosal on channel activity
Modulation of the conductance of a 2,2′-bipyridine-functionalized peptidic ion channel by Ni2+
An α-helical amphipathic peptide with the sequence H2N-(LSSLLSL)3-CONH2 was obtained by solid phase synthesis and a 2,2′-bipyridine was coupled to its N-terminus, which allows complexation of Ni2+. Complexation of the 2,2′-bipyridine residues was proven by UV/Vis spectroscopy. The peptide helices were inserted into lipid bilayers (nano black lipid membranes, nano-BLMs) that suspend the pores of porous alumina substrates with a pore diameter of 60 nm by applying a potential difference. From single channel recordings, we were able to distinguish four distinct conductance states, which we attribute to an increasing number of peptide helices participating in the conducting helix bundle. Addition of Ni2+ in micromolar concentrations altered the conductance behaviour of the formed ion channels in nano-BLMs considerably. The first two conductance states appear much more prominent demonstrating that the complexation of bipyridine by Ni2+ results in a considerable confinement of the observed multiple conductance states. However, the conductance levels were independent of the presence of Ni2+. Moreover, from a detailed analysis of the open lifetimes of the channels, we conclude that the complexation of Ni2+ diminishes the frequency of channel events with larger open times
Antimicrobial activity of new green-functionalized oxazoline-based oligomers against clinical isolates
Background: The search for new antimicrobial compounds able to overcome the global issue of microbial resistance
to antibiotics is a priority worldwide. Moreover, several commensal microorganisms have been increasingly associated
to opportunistic microbial infections. Having previously disclosed the green synthesis and preliminary characterization
of the oligomers [linear oligo(ethylenimine) hydrochloride and oligo(2-methyl-2-oxazoline) quaternized with N,Ndimethyldodecylamine]
we herein report on the screening of these oligomers against a battery of 69 clinical isolates
of Aerococcus spp., Candida spp., Staphylococcus spp. and Streptococcus spp.
Findings: The isolates’ susceptibility to both oligomers was evaluated by determining their minimal inhibitory concentration
(MIC) and the biocidal effectiveness of each compound was further confirmed through spectrophotometric
measurements and fluorescence microscopy. The MIC values of the 69 isolates were highly variable, yet favourably
comparable with those of other antimicrobial polymers. The viability assays resulted in 100% of microbial killing rate
after only 5 min, highlighting the promising antimicrobial action of these oligomers.
Conclusions: Though further studies are required, evidence suggests that a strong effort should be done in order
to confirm these compounds as valid alternatives for several clinical applications. This is reinforced by their well
described biocompatibility with human tissues and by their proposed mechanism of action which difficult the development
of microbial resistance to these compounds
Controlled delivery of membrane proteins to artificial lipid bilayers by nystatin–ergosterol modulated vesicle fusion
Bilayer lipid composition modulates the activity of dermaseptins, polycationic antimicrobial peptides
(IF : 2,409)International audienceThe primary targets of defense peptides are plasma membranes, and the induced irreversible depolarization is sufficient to exert antimicrobial activity although secondary modes of action might be at work. Channels or pores underlying membrane permeabilization are usually quite large with single-channel conductances two orders of magnitude higher than those exhibited by physiological channels involved, e.g., in excitability. Accordingly, the ion specificity and selectivity are quite low. Whereas, e.g., peptaibols favor cation transport, polycationic or basic peptides tend to form anion-specific pores. With dermaseptin B2, a 33 residue long and mostly a-helical peptide isolated from the skin of the South American frog Phyllomedusa bicolor, we found that the ion specificity of its pores induced in bilayers is modulated by phospholipidcharged headgroups. This suggests mixed lipid–peptide pore lining instead of the more classical barrel–stave model. Macroscopic conductance is nearly voltage independent, and concentration dependence suggests that the pores are mainly formed by dermaseptin tetramers. The two most probable single-channel events are well resolved at 200 and 500 pS (in 150 mM NaCl) with occasional other equally spaced higher or lower levels. In contrast to previous molecular dynamics previsions, this study demonstrates that dermaseptins are able to form pores, although a related analog (B6) failed to induce any significant conductance. Finally, the model of the pore we present accounts for phospholipid headgroups intercalated between peptide helices lining the pore and for one of the most probable single-channel conductance
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