Abstract
Amphidinol 3 (AM3) is an anti-fungal polyene extracted from a marine dinoflagellate. Here, we examined the ion channel activity and membrane-embedded structure of AM3 using a lipid bilayer method and atomic force microscopy (AFM). AM3 exhibited large-conductance (~1 nS) and non-selective single-channel activity only when sterols were present in the membrane leaflet of the AM3-added side. The variable conductance suggests the formation of a multimeric barrel-stave pore. At high AM3 concentrations, giant-conductance “jumbo” channels (~40 nS) emerged. AFM revealed a thicker raft-like membrane phase with the appearance of a wrinkled surface, in which phase pores (diameter: ~10 nm) were observed. The flip-flop of ergosterol occurred only after the appearance of the jumbo channel, indicating that the jumbo channel induced a continuity between the outer and inner leaflets of the membrane: a feature characteristic of toroidal-like pores. Thus, AM3 forms different types of sterol-aided polymorphic channels in a concentration dependent manner.
Highlights
We characterized the channel activity of Amphidinol 3 (AM3) using a lipid bilayer method[11] and its membrane-embedded structure using atomic force microscopy (AFM)[12,13,14] at the single-channel level
We found that AM3, with its unique structure, exhibited unprecedented and wide-spectrum features of channel activity
We first examined the single-channel activity of AM3 in the ergosterol-containing membrane
Summary
We characterized the channel activity of AM3 using a lipid bilayer method[11] and its membrane-embedded structure using atomic force microscopy (AFM)[12,13,14] at the single-channel level. We found that AM3, with its unique structure, exhibited unprecedented and wide-spectrum features of channel activity. At a high AM3 concentration, phase separation[15] occurred in the AM3-embedded membrane, similar to sterol-containing rafts[16, 17]. The unique features of AM3, including its polymorphic channel activities and ability to induce membrane rafts, were discussed in relation to the toxic actions in the targeted cells as well as an advanced tool for membrane manipulation
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