The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.

The ability of the shark antimicrobial aminosterol squalamine to induce the leakage of polar fluorescent dyes from large unilamellar phospholipid vesicles (LUVs) has been measured. Micromolar squalamine causes leakage of carboxyfluorescein (CF) from vesicles prepared from the anionic phospholipids phosphatidylglycerol (PG), phosphatidylserine (PS), and cardiolipin. Binding analyses based on the leakage data show that squalamine has its highest affinity to phosphatidylglycerol membranes, followed by phosphatidylserine and cardiolipin membranes. Squalamine will also induce the leakage of CF from phosphatidylcholine (PC) LUVs at low phospholipid concentrations. At high phospholipid concentrations, the leakage of CF from PC LUVs deviates from a simple dose-response relationship, and it appears that some of the squalamine can no longer cause leakage. Fluorescent dye leakage generated by squalamine is graded, suggesting the formation of a discrete membrane pore rather than a generalized disruption of vesicular membranes. By using fluorescently labeled dextrans of different molecular weight, material with molecular weight /=10,000 is retained. Negative stain electron microscopy of squalamine-treated LUVs shows that squalamine decreases the average vesicular size in a concentration-dependent manner. Squalamine decreases the size of vesicles containing anionic phospholipid at a lower squalamine/lipid molar ratio than pure PC LUVs. In a centrifugation assay, squalamine solubilizes phospholipid, but only at significantly higher squalamine/phospholipid ratios than required for either dye leakage or vesicle size reduction. Squalamine solubilizes PC at lower squalamine/phospholipid ratios than PG. We suggest that squalamine complexes with phospholipid to form a discrete structure within the bilayers of LUVs, resulting in the transient leakage of small encapsulated molecules. At higher squalamine/phospholipid ratios, these structures release from the bilayers and aggregate to form either new vesicles or squalamine/phospholipid mixed micelles.

Main Author: Selinsky, Barry.
Other Authors: Zhou, Zhao., Fojtik, Kristin., Jones, Stephen., Dollahon, Norman., Shinnar, Ann.
Format: Villanova Faculty Authorship
Language: English
Published: 1997
Online Access: http://ezproxy.villanova.edu/login?url=https://digital.library.villanova.edu/Item/vudl:175908
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dc_source_str_mv Biochemica Biophysica Acta 1370, 1998, 218-234.
author Selinsky, Barry.
author_facet_str_mv Selinsky, Barry.
Zhou, Zhao.
Fojtik, Kristin.
Jones, Stephen.
Dollahon, Norman.
Shinnar, Ann.
author_or_contributor_facet_str_mv Selinsky, Barry.
Zhou, Zhao.
Fojtik, Kristin.
Jones, Stephen.
Dollahon, Norman.
Shinnar, Ann.
author_s Selinsky, Barry.
spellingShingle Selinsky, Barry.
The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
author-letter Selinsky, Barry.
author_sort_str Selinsky, Barry.
author2 Zhou, Zhao.
Fojtik, Kristin.
Jones, Stephen.
Dollahon, Norman.
Shinnar, Ann.
author2Str Zhou, Zhao.
Fojtik, Kristin.
Jones, Stephen.
Dollahon, Norman.
Shinnar, Ann.
dc_title_str The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
title The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
title_short The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
title_full The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
title_fullStr The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
title_full_unstemmed The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
collection_title_sort_str aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
title_sort aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
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description The ability of the shark antimicrobial aminosterol squalamine to induce the leakage of polar fluorescent dyes from large unilamellar phospholipid vesicles (LUVs) has been measured. Micromolar squalamine causes leakage of carboxyfluorescein (CF) from vesicles prepared from the anionic phospholipids phosphatidylglycerol (PG), phosphatidylserine (PS), and cardiolipin. Binding analyses based on the leakage data show that squalamine has its highest affinity to phosphatidylglycerol membranes, followed by phosphatidylserine and cardiolipin membranes. Squalamine will also induce the leakage of CF from phosphatidylcholine (PC) LUVs at low phospholipid concentrations. At high phospholipid concentrations, the leakage of CF from PC LUVs deviates from a simple dose-response relationship, and it appears that some of the squalamine can no longer cause leakage. Fluorescent dye leakage generated by squalamine is graded, suggesting the formation of a discrete membrane pore rather than a generalized disruption of vesicular membranes. By using fluorescently labeled dextrans of different molecular weight, material with molecular weight </=4000 g/mol is released from vesicles by squalamine, but material with molecular weight >/=10,000 is retained. Negative stain electron microscopy of squalamine-treated LUVs shows that squalamine decreases the average vesicular size in a concentration-dependent manner. Squalamine decreases the size of vesicles containing anionic phospholipid at a lower squalamine/lipid molar ratio than pure PC LUVs. In a centrifugation assay, squalamine solubilizes phospholipid, but only at significantly higher squalamine/phospholipid ratios than required for either dye leakage or vesicle size reduction. Squalamine solubilizes PC at lower squalamine/phospholipid ratios than PG. We suggest that squalamine complexes with phospholipid to form a discrete structure within the bilayers of LUVs, resulting in the transient leakage of small encapsulated molecules. At higher squalamine/phospholipid ratios, these structures release from the bilayers and aggregate to form either new vesicles or squalamine/phospholipid mixed micelles.
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dc.title The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.
dc.creator Selinsky, Barry.
Zhou, Zhao.
Fojtik, Kristin.
Jones, Stephen.
Dollahon, Norman.
Shinnar, Ann.
dc.description The ability of the shark antimicrobial aminosterol squalamine to induce the leakage of polar fluorescent dyes from large unilamellar phospholipid vesicles (LUVs) has been measured. Micromolar squalamine causes leakage of carboxyfluorescein (CF) from vesicles prepared from the anionic phospholipids phosphatidylglycerol (PG), phosphatidylserine (PS), and cardiolipin. Binding analyses based on the leakage data show that squalamine has its highest affinity to phosphatidylglycerol membranes, followed by phosphatidylserine and cardiolipin membranes. Squalamine will also induce the leakage of CF from phosphatidylcholine (PC) LUVs at low phospholipid concentrations. At high phospholipid concentrations, the leakage of CF from PC LUVs deviates from a simple dose-response relationship, and it appears that some of the squalamine can no longer cause leakage. Fluorescent dye leakage generated by squalamine is graded, suggesting the formation of a discrete membrane pore rather than a generalized disruption of vesicular membranes. By using fluorescently labeled dextrans of different molecular weight, material with molecular weight </=4000 g/mol is released from vesicles by squalamine, but material with molecular weight >/=10,000 is retained. Negative stain electron microscopy of squalamine-treated LUVs shows that squalamine decreases the average vesicular size in a concentration-dependent manner. Squalamine decreases the size of vesicles containing anionic phospholipid at a lower squalamine/lipid molar ratio than pure PC LUVs. In a centrifugation assay, squalamine solubilizes phospholipid, but only at significantly higher squalamine/phospholipid ratios than required for either dye leakage or vesicle size reduction. Squalamine solubilizes PC at lower squalamine/phospholipid ratios than PG. We suggest that squalamine complexes with phospholipid to form a discrete structure within the bilayers of LUVs, resulting in the transient leakage of small encapsulated molecules. At higher squalamine/phospholipid ratios, these structures release from the bilayers and aggregate to form either new vesicles or squalamine/phospholipid mixed micelles.
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