Molecular Aspects of Polyene- and Sterol-Dependent Pore Formation in Thin Lipid Membranes

@article{Dennis1970MolecularAO,
  title={Molecular Aspects of Polyene- and Sterol-Dependent Pore Formation in Thin Lipid Membranes},
  author={Vincent W. Dennis and Nancy W. Stead and Thomas E. Andreoli},
  journal={The Journal of General Physiology},
  year={1970},
  volume={55},
  pages={375 - 400}
}
Amphotericin B modifies the permeability properties of thin lipid membranes formed from solutions containing sheep red cell phospholipids and cholesterol. At 10-6 M amphotericin B, the DC membrane resistance fell from ≈108 to ≈102 ohm-cm2, and the membranes became Cl--, rather than Na+-selective; the permeability coefficients for hydrophilic nonelectrolytes increased in inverse relationship to solute size, and the rate of water flow during osmosis increased 30-fold. These changes may be… 
Single ionic channels induced in lipid bilayers by polyene antibiotics amphotericin B and nystatine
TLDR
It is concluded that amphotericin B and nystatine form aqueous pores with an effective radius of approximately 4 Å in thin lipid membranes and the changes in membrane conductance connected with the formation of a single pore have not yet been observed.
Transient permeability induced by alkyl derivatives of amphotericin B in lipid membranes.
TLDR
It was proposed that the antibiotic oligomers incorporate into the membrane from the aqueous phase, form channels aggregating with cholesterol, and then dissociate in the bilayer into non-active degraded oligomeric or monomeric forms.
Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. I. Specificity of the membrane permeability changes induced by the polyene antibiotics.
TLDR
Only those sterols which had 3β-OH group, a planar molecule and hydrophobic side chain at C17 were able to interact with these polyene antibiotics and thereby enhance the membrane permeability.
Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. 3. Molecular structure of the polyene antibiotic-cholesterol complexes.
TLDR
Mechanisms of the polyene antibiotic induced permeability changes in membranes are proposed based on the analysis of the complexes of cholesterol, amphotericin B, nystatin, etruscomycin and pimaricin, which can be built with space-filling models.
Polyene antibiotic-sterol interactions in membranes of Acholesplasma laidlawii cells and lecithin liposomes. II. Temperature dependence of the polyene antibiotic-sterol complex formation.
TLDR
These experiments prove that the polyene antibiotics form complexes with cholesterol in the A. laidlawii cell membrane, and it is suggested that filipin interacts first with cholesterol throughout the membrane forming primary Filipin-cholesterol complexes.
Interaction of the polyene antibiotics with lipid bilayer vesicles containing cholesterol.
TLDR
Despite the fact that cholesterol is required for antibiotic activity, the NMR spectra prior to vesicle destruction show no changes indicative of an antibiotic-induced reversal of cholesterol restriction of phosphatidylcholine mobility, which indicates a well defined antibiotic : cholesterol interaction stoichiometry.
Selective release of non-electrolytes from liposomes upon perturbation of bilayers by temperature change or polyene antibiotics.
TLDR
A new system for assaying the permeability characteristics of liposomes was established using Amicon cells equipped with a membrane filter (pore size, 0.3 micrometer) and results were obtained on the barrier properties of multilamellar liposome modified by various treatments.
Effect of Membrane Structure on the Action of Polyenes: I. Nystatin Action in Cholesterol- and Ergosterol-Containing Membranes
TLDR
The present results and those of a companion paper lead us to propose that membrane structure is the determining factor for drug selectivity in membranes with different sterols.
How do ionic channel properties depend on the structure of polyene antibiotic molecules?
TLDR
A study has been made of the properties of ionic channels formed in phospholipid-cholesterol bilayers by polyene antibiotics of various molecular structures and found that conductance and selectivity of an open channel are not influenced by changes in the charged groups.
Properties of amphotericin B channels in a lipid bilayer.
TLDR
A simple model having only one site for an ion was shown to represent satisfactorily an open channel behaviour under different conditions, indicating preferential but not ideal anionic selectivity of a single channel.
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TLDR
Data suggest that amphotericin B or nystatin may interact with membrane-bound sterols to produce multimolecular complexes which greatly enhance the permeability of such membranes for anions, acetate, and, to a lesser degree, cations (Na+, K+, Li+).
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TLDR
These data were compatible with the hypothesis that the interactions of amphotericin B with membrane-bound cholesterol result in the formation of pores whose equivalent radii are in the range 7 to 10 A, with the effective hydrodynamic radii of the solutes tested.
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It was found that the thin lipid membranes have ionic permeability properties which are vastly different from those of intact HK and LK sheep red cell membranes, and the Na + and K + transport properties of the two genetic types of sheep red cells are significantly different.
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The permeability and electrical properties of thin lipid membranes are presented, and the changes induced in these properties by several agents added to the aqueous phases after the membranes have formed are discussed.
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TLDR
Data from this study were consistent with the hypothesis that the polyenes induce a spatial reorientation of the sterol, and the mechanism by which the polyeaes produce such marked permeability alterations is examined.
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TLDR
The data are consistent with the hypothesis that valinomycin can interact with appropriately sized cations to increase their membrane permeability, perhaps by forming hydrogen bonds between the solvation shell of the cations and carbonyl oxygens in the val inomycin molecule which are directed toward the aperture of the ring.
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TLDR
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TLDR
The high degree of membrane cation selectivity was tentatively attributed to the negatively charged phospholipids (phosphatidylethanolamine and phosphatidylserine) present in the lipid extract.
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