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Fengycin induces ion channels in lipid bilayers mimicking target fungal cell membranes
Anastasiia A Zakharova1, Svetlana S Efimova2, Valery V Malev1,3
1Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, 194064, Russian Federation.
Abstract:
The one-sided addition of fengycin (FE) to planar lipid bilayers mimicking target fungal cell membranes up to 0.1 to 0.5 μM in the membrane bathing solution leads to the formation of well-defined and well-reproducible single-ion channels of various conductances in the picosiemens range. FE channels were characterized by asymmetric conductance-voltage characteristic. Membranes treated with FE showed nonideal cationic selectivity in potassium chloride bathing solutions. The membrane conductance induced by FE increased with the second power of the lipopeptide aqueous concentration, suggesting that at least FE dimers are involved in the formation of conductive subunits. The pore formation ability of FE was not distinctly affected by the molecular shape of membrane lipids but strongly depended on the presence of negatively charged species in the bilayer. FE channels were characterized by weakly pronounced voltage gating. Small molecules known to modify the transmembrane distribution of electrical potential and the lateral pressure profile were used to modulate the channel-forming activity of FE. The observed effects of membrane modifiers were attributed to changes in lipid packing and lipopeptide oligomerization in the membrane.
Insights
Fengycin (FE) forms ion channels in fungal cell membranes, acting as dimers. Its pore formation depends on negatively charged lipids and is modulated by membrane modifiers.
Area of Science:
- Biophysics
- Membrane Biology
- Antimicrobial Peptides
Background:
- Fungal infections pose a significant threat, necessitating the development of novel antifungal agents.
- Lipopeptides, such as fengycin (FE), are known for their membrane-disrupting properties.
- Understanding the mechanism of FE interaction with cell membranes is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the channel-forming activity of fengycin (FE) in planar lipid bilayers.
- To characterize the biophysical properties of FE-induced ion channels.
- To explore the influence of lipid composition and membrane modifiers on FE channel formation.
Main Methods:
- Incorporation of fengycin (FE) into planar lipid bilayers mimicking fungal cell membranes.
- Electrophysiological recordings to measure ion channel conductance and voltage-current characteristics.
- Systematic variation of lipid composition and addition of membrane modifiers.
Main Results:
- Fengycin (FE) forms well-defined, single-ion channels with conductances in the picosiemens range.
- FE channels exhibit asymmetric conductance-voltage characteristics and nonideal cationic selectivity.
- Channel formation is dependent on FE concentration (suggesting dimer involvement), negatively charged lipids, and is modulated by membrane modifiers affecting lipid packing and FE oligomerization.
Conclusions:
- Fengycin (FE) acts as a pore-forming agent in lipid bilayers, likely through dimer formation.
- The channel activity of FE is sensitive to membrane properties, particularly lipid charge and packing.
- This study provides insights into the molecular mechanism of fengycin's antifungal action at the membrane level.
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