Interaction of Amphotericin B and Nystatin with Phospholipid Bilayer Membranes: Effect of Cholesterol

1975 ◽  
Vol 53 (6) ◽  
pp. 1072-1079 ◽  
Author(s):  
Michael A. Singer
Keyword(s):  
Membrane Fluidity ◽  
Amphotericin B ◽  
Local Anesthetics ◽  
Cholesterol Content ◽  
Phospholipid Bilayer ◽  
High Cholesterol ◽  
Na Transport ◽  
Bilayer Membranes ◽  
Multilamellar Liposomes ◽  
Transmembrane Channels

Sodium-22 efflux was measured in multilamellar liposomes, exposed to one of the two polyene antibiotics amphotericin B or nystatin. Polyene mediated 22Na transport progressively rises with membrane sterol concentrations up to about 20 mol %, but falls with higher cholesterol concentrations. The polyene induced 22Na movement in cholesterol rich liposomes could be 'restored' by the addition of either dibucaine or propranolol (two local anesthetics) to the aqueous solution. These observations are interpreted in terms of the model of De Kruijff and Demel (Biochim. Biophys. Acta, 339, 57–70, 1974). In this model, nystatin and amphotericin B first complex with cholesterol and then these complexes aggregate to form transmembrane channels. It is here proposed that the aggregation of these complexes is inhibited by a high cholesterol content (decreased membrane fluidity) but that the two local anesthetics, by disrupting phospholipid–sterol interactions (increased membrane fluidity), can 'restore' this process of aggregation.

Interaction of four local anesthetics with phospholipid bilayer membranes: permeability effects and possible mechanisms

1980 ◽  
Vol 58 (10) ◽  
pp. 815-821 ◽  
Author(s):  
Michael A. Singer ◽  
Mahendra K. Jain
Keyword(s):  
Local Anesthetics ◽  
Temperature Curve ◽  
Phospholipid Bilayer ◽  
Lipid Phase ◽  
Lipid Phase Transition ◽  
Bilayer Membranes ◽  
Multilamellar Liposomes ◽  
Preferential Binding ◽  
Lower Temperature ◽  
Dicetyl Phosphate

Sodium 22 efflux was measured, at various temperatures, in the presence of different local anesthetics (dibucaine, tetracaine, benzocaine, procaine) in multilamellar liposomes composed of saturated phosphatidylcholines and dicetyl phosphate. These liposomes display a permeability maximum in the temperature region of their respective phase transitions. Local anesthetics cause this permeability maximum to occur at a lower temperature and also increase its magnitude. Binding of the anesthetics to these liposomes displays a biphasic temperature curve with a maximum in the vicinity of the transition temperature. In addition there appears to be a linear relationship between aqueous anesthetic concentrations causing equal permeability effects and corresponding membrane concentrations. All of the anesthetics decrease the cooperativity of the lipid phase transition and this is probably an important factor underlying induced permeability effects. However several observations suggest that additional factors are also important and we have postulated that one such factor is the preferential binding of the anesthetics to phase boundary regions.

Interaction of the Organochlorine Pesticide Dieldrin with Phospholipid Bilayers

1997 ◽  
Vol 52 (7-8) ◽  
pp. 450-458 ◽  
Author(s):  
M. Suwalsky ◽  
M. Benites ◽  
F. Villena ◽  
F. Aguilar ◽  
C. P. Sotomayor
Keyword(s):  
Cholesterol Content ◽  
Phospholipid Bilayer ◽  
Organochlorine Insecticide ◽  
Molecular Models ◽  
Human Beings ◽  
X Ray Diffraction ◽  
High Cholesterol ◽  
Large Unilamellar Vesicles ◽  
Living Organisms ◽  
Cell Membrane Level

Abstract Dieldrin is an organochlorine insecticide highly toxic for human beings. Although its exact mechanism of action is not well known, there is evidence that it acts at the cell membrane level. In fact, the lipophilicity of the pesticide as well as that of the phospholipid bilayer present in biological membranes makes the latter a most likely target for the interaction of dieldrin with living organisms. In order to evaluate its perturbing effect upon cell membranes the pesticide was made to interact with human erythrocytes and molecular models. These studies were performed by scanning electron microscopy on erythrocytes, fluorescence spectroscopy on dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles and X-ray diffraction on multilayers of dimirystoylphosphatidylcholine (DMPC) and dimyristoyl-phosphatidylethanolamine (DMPE). It was observed that dieldrin particularly interacted with DMPC liposomes and multilayers perturbing its molecular arrangements. However, no effect was noticed on erythrocytes, which might be due to its high cholesterol content.

scholarly journals On the one-sided action of amphotericin B on lipid bilayer membranes.

1996 ◽  
Vol 107 (1) ◽  
pp. 69-78 ◽  
Author(s):  
R A Brutyan ◽  
P McPhie
Keyword(s):  
Amphotericin B ◽  
Single Channel ◽  
Membrane Surface ◽  
Classical Model ◽  
Ionic Channels ◽  
Phospholipid Bilayer ◽  
Lipid Bilayer Membranes ◽  
Polyene Antibiotic ◽  
Bilayer Membranes ◽  
The One

The one-sided action of the polyene antibiotic, amphotericin B, on phospholipid bilayer membranes formed from synthetic phosphatidylcholines (DOPC and DPhPC) and sterols (ergosterol and cholesterol), has been investigated. We found formation of well-defined ionic channels for both sterols and not only for ergosterol-containing membranes (Bolard, J., P. Legrand, F. Heitz, and B. Cybulska. 1991. Biochemistry. 30:5707-5715). Characteristics of these channels were studied in the presence of different salts. It was found that the channels have comparable conductances but different lifetimes that are approximately 100-fold less in cholesterol-containing membranes than in ergosterol-containing ones. Channel blocking by tetraethylammonium (TEA) ions shows that TEA blockage of channels in the presence of cholesterol increases their lifetimes in analogy to the lengthening of lifetimes of protein channels blocked by local anesthetics (Neher, E., and J. H. Steinbach. 1978. J. Physiol. 277: 153-176). However, the effect of the blocker on single-channel conductance is very close for both sterols. The data support the classical model of amphotericin B pore formation from complexes initially lying on the membrane surface as nonconducting prepores. We explain the antibiotic's cytotoxic selectivity by differences in the lifetimes of the channels formed with different sterols and suggest that phosphatidylcholine-sterol membranes can be used as a tool for rapid estimation of polyene antibiotic cytotoxicity.

scholarly journals Fusion of phospholipid vesicles with planar phospholipid bilayer membranes. II. Incorporation of a vesicular membrane marker into the planar membrane.

1980 ◽  
Vol 75 (3) ◽  
pp. 251-270 ◽  
Author(s):  
F S Cohen ◽  
J Zimmerberg ◽  
A Finkelstein
Keyword(s):  
Divalent Cations ◽  
Phospholipid Bilayer ◽  
Phospholipid Vesicles ◽  
Osmotic Gradient ◽  
Bilayer Membranes ◽  
Fusion Procedure ◽  
Vesicular Membrane ◽  
Membrane Contact ◽  
Planar Membrane ◽  
Planar Membranes

Fusion of multilamellar phospholipid vesicles with planar phospholipid bilayer membranes was monitored by the rate of appearance in the planar membrane of an intrinsic membrane protein present in the vesicle membranes. An essential requirement for fusion is an osmotic gradient across the planar membrane, with the cis side (the side containing the vesicles) hyperosmotic to the opposite (trans) side; for substantial fusion rates, divalent cation must also be present on the cis side. Thus, the low fusion rates obtained with 100 mM excess glucose in the cis compartment are enhanced orders of magnitude by the addition of 5-10 mM CaCl2 to the cis compartment. Conversely, the rapid fusion rates induced by 40 mM CaCl2 in the cis compartment are completely suppressed when the osmotic gradient (created by the 40 mM CaCl2) is abolished by addition of an equivalent amount of either CaCl2, NaCl, urea, or glucose to the trans compartment. We propose that fusion occurs by the osmotic swelling of vesicles in contact with the planar membrane, with subsequent rupture of the vesicular and planar membranes in the region of contact. Divalent cations catalyze this process by increasing the frequency and duration of vesicle-planar membrane contact. We argue that essentially this same osmotic mechanism drives biological fusion processes, such as exocytosis. Our fusion procedure provides a general method for incorporating and reconstituting transport proteins into planar phospholipid bilayer membranes.

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