scholarly journals The Interaction of Polyene Antibiotics with Thin Lipid Membranes

1968 ◽  
Vol 52 (2) ◽  
pp. 300-325 ◽  
Author(s):  
Thomas E. Andreoli ◽  
Marcia Monahan
Keyword(s):  
Amphotericin B ◽  
Lipid Membranes ◽  
Sheep Erythrocyte ◽  
Cholesterol Content ◽  
Transference Numbers ◽  
Ionic Selectivity ◽  
Antibiotic Concentration ◽  
Polyene Antibiotics ◽  
Cyclic Polyene ◽  
Membrane Bound

Optically black, thin lipid membranes prepared from sheep erythrocyte lipids have a high dc resistance (Rm ≅ 108 ohm-cm2) when the bathing solutions contain NaCl or KCl. The ionic transference numbers (Ti) indicate that these membranes are cation-selective (TNa ≅ 0.85; TCl ≅ 0.15). These electrical properties are independent of the cholesterol content of the lipid solutions from which the membranes are formed. Nystatin, and probably amphotericin B, are cyclic polyene antibiotics containing ≈36 ring atoms and a free amino and carboxyl group. When the lipid solutions used to form membranes contained equimolar amounts of cholesterol and phospholipid, these antibiotics reduced Rm to ≈102 ohm-cm2; concomitantly, TCl became ≅0.92. The slope of the line relating log Rm and log antibiotic concentration was ≅4.5. Neither nystatin (2 x 10-5 M) nor amphotericin B (2 x 10-7 M) had any effect on membrane stability. The antibiotics had no effect on Rm or membrane permselectivity when the lipids used to form membranes were cholesterol-depleted. Filipin (10-5 M), an uncharged polyene with 28 ring atoms, produced striking membrane instability, but did not affect Rm or membrane ionic selectivity. These 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 (Cl-, acetate), and, to a lesser degree, cations (Na+, K+, Li+).

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

1970 ◽  
Vol 55 (3) ◽  
pp. 375-400 ◽  
Author(s):  
Vincent W. Dennis ◽  
Nancy W. Stead ◽  
Thomas E. Andreoli
Keyword(s):  
Amphotericin B ◽  
Lipid Membranes ◽  
Free Sterol ◽  
Pore Formation ◽  
Membrane Resistance ◽  
Ionic Selectivity ◽  
Ring Compounds ◽  
Permeability Changes ◽  
Membrane Bound ◽  
Molecular Aspects

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 rationalized by assuming that the interaction of amphotericin B with membrane-bound sterol resulted in the formation of aqueous pores. N-acetylamphotericin B and the methyl ester of N-acetylamphotericin B, but not the smaller ring compounds, filipin, rimocidin, and PA-166, produced comparable permeability changes in identical membranes, and amphotericin B and its derivatives produced similar changes in the properties of membranes formed from phospholipid-free sterol solutions. However, amphotericin B did not affect ionic selectivity or water and nonelectrolyte permeability in membranes formed from solutions containing phospholipids and no added cholesterol, or when cholesterol was replaced by either cholesterol palmitate, dihydrotachysterol, epicholesterol, or Δ5-cholesten-3-one. Phospholipid-free sterol membranes exposed to amphotericin B or its derivatives were anion-selective, but the degree of Cl- selectivity varied among the compounds, and with the aqueous pH. The data are discussed with regard to, first, the nature of the polyene-sterol interactions which result in pore formation, and second, the functional groups on amphotericin B responsible for membrane anion selectivity.

scholarly journals The Formation and Properties of Thin Lipid Membranes from HK and LK Sheep Red Cell Lipids

1967 ◽  
Vol 50 (6) ◽  
pp. 1729-1749 ◽  
Author(s):  
Thomas E. Andreoli ◽  
J. Andrew Bangham ◽  
Daniel C. Tosteson
Keyword(s):  
Lipid Membranes ◽  
Transference Number ◽  
Cholesterol Content ◽  
Membrane Voltage ◽  
Transference Numbers ◽  
Molar Ratio ◽  
Membrane Thickness ◽  
High Potassium ◽  
Cation Selectivity ◽  
High Degree

Lipids were obtained from high potassium (HK) and low potassium (LK) sheep red cells by sequential extraction of the erythrocytes with isopropanol-chloroform, chloroform-methanol-0.1 M KCl, and chloroform. The extract contained cholesterol and phospholipid in a molar ratio of 0.8:1.0, and less than 1% protein contaminant. Stable thin lipid membranes separating two aqueous compartments were formed from an erythrocyte lipid-hydrocarbon solution, and had an electrical resistance of ∼108 ohm-cm2 and a capacitance of 0.38–0.4 µf/cm2. From the capacitance values, membrane thickness was estimated to be 46–132 A, depending on the assumed value for the dielectric constant (2.0–4.5). Membrane voltage was recorded in the presence of ionic (NaCl and/or KCl) concentration gradients in the solutions bathing the membrane. The permeability of the membrane to Na+, K+, and Cl- (expressed as the transference number, Tion) was computed from the steady-state membrane voltage and the activity ratio of the ions in the compartments bathing the membrane. TNa and TK were approximately equal (∼0.8) and considerably greater than TCl (∼0.2). The ionic transference numbers were independent of temperature, the hydrocarbon solvent, the osmolarity of the solutions bathing the membranes, and the cholesterol content of the membranes, over the range 21–38°C. The high degree of membrane cation selectivity was tentatively attributed to the negatively charged phospholipids (phosphatidylethanolamine and phosphatidylserine) present in the lipid extract.

scholarly journals The Ion Permeability Induced in Thin Lipid Membranes by the Polyene Antibiotics Nystatin and Amphotericin B

1970 ◽  
Vol 56 (1) ◽  
pp. 100-124 ◽  
Author(s):  
Albert Cass ◽  
Alan Finkelstein ◽  
Vivian Krespi
Keyword(s):  
Amphotericin B ◽  
Lipid Membranes ◽  
Ion Selectivity ◽  
Membrane Conductance ◽  
Temperature Sensitive ◽  
Hydroxyl Groups ◽  
Large Power ◽  
Polyene Antibiotics ◽  
Cation Selectivity ◽  
Anion Selectivity

Characteristics of nystatin and amphotericin B action on thin (<100 A) lipid membranes are: (a) micromolar amounts increase membrane conductance from 10-8 to over 10-2 Ω-1 cm-2; (b) such membranes are (non-ideally) anion selective and discriminate among anions on the basis of size; (c) membrane sterol is required for action; (d) antibiotic presence on both sides of membrane strongly favors action; (e) conductance is proportional to a large power of antibiotic concentration; (f) conductance decreases ∼104 times for a 10°C temperature rise; (g) kinetics of antibiotic action are also very temperature sensitive; (h) ion selectivity is pH independent between 3 and 10, but (i) activity is reversibly lost at high pH; (j) methyl ester derivatives are fully active; N-acetyl and N-succinyl derivatives are inactive; (k) current-voltage characteristic is nonlinear when membrane separates nonidentical salt solutions. These characteristics are contrasted with those of valinomycin. Observations (a)–(g) suggest that aggregates of polyene and sterol from opposite sides of the membrane interact to create aqueous pores; these pores are not static, but break up (melt) and reform continuously. Mechanism of anion selectivity is obscure. Observations (h)–(j) suggest—NH3+ is important for activity; it is probably not responsible for selectivity, particularly since four polyene antibiotics, each containing two—NH3+ groups, induce ideal cation selectivity. Possibly the many hydroxyl groups in nystatin and amphotericin B are responsible for anion selectivity. The effects of polyene antibiotics on thin lipid membranes are consistent with their action on biological membranes.

scholarly journals The Effect of Amphotericin B on the Water and Nonelectrolyte Permeability of Thin Lipid Membranes

1969 ◽  
Vol 53 (2) ◽  
pp. 133-156 ◽  
Author(s):  
Thomas E. Andreoli ◽  
Vincent W. Dennis ◽  
Ann M. Weigl
Keyword(s):  
Amphotericin B ◽  
Lipid Membranes ◽  
Permeability Coefficient ◽  
Circular Cylinders ◽  
Osmotic Water Permeability ◽  
Polyene Antibiotic ◽  
Water Permeability Coefficient ◽  
Osmotic Water ◽  
Membrane Bound ◽  
Nonelectrolyte Permeability

This paper reports the effects of amphotericin B, a polyene antibiotic, on the water and nonelectrolyte permeability of optically black, thin lipid membranes formed from sheep red blood cell lipids dissolved in decane. The permeability coefficients for the diffusion of water and nonelectrolytes (PDDi) were estimated from unidirectional tracer fluxes when net water flow (Jw) was zero. Alternatively, an osmotic water permeability coefficient (Pf) was computed from Jw when the two aqueous phases contained unequal solute concentrations. In the absence of amphotericin B, when the membrane solutions contained equimolar amounts of cholesterol and phospholipid, Pf was 22.9 ± 4.6 µsec-1 and PDDHDH2O was 10.8 ± 2.4 µsec-1. Furthermore, PDDi was < 0.05 µsec-1 for urea, glycerol, ribose, arabinose, glucose, and sucrose, and σi, the reflection coefficient of each of these solutes was one. When amphotericin B (10-6 M) was present in the aqueous phases and the membrane solutions contained equimolar amounts of cholesterol and phospholipid, PDDHDH2O was 18.1 ± 2.4 µsec-1; Pf was 549 ± 143 µsec-1 when glucose, sucrose, and raffinose were the aqueous solutes. Concomitantly, PDDi varied inversely, and σi directly, with the effective hydrodynamic radii of the solutes tested. These polyene-dependent phenomena required the presence of cholesterol in the membrane solutions. These data were analyzed in terms of restricted diffusion and filtration through uniform right circular cylinders, and 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 10.5 A.

scholarly journals Enzyme Catalysis Enhances Lateral Lipid Motility and Directional Particle Transport on Membranes

2021 ◽  
Author(s):  
Ambika Somasundar ◽  
Niladri Sekhar Mandal ◽  
Ayusman Sen
Keyword(s):  
Lipid Membranes ◽  
Enzyme Catalysis ◽  
Lateral Diffusion ◽  
Cholesterol Content ◽  
Supported Bilayers ◽  
Membrane Fluctuations ◽  
Diffusion Enhancement ◽  
Membrane Bound ◽  
Passive Tracers ◽  
Membrane Bound Enzymes

The dynamic interplay between the composition of lipid membranes and the behavior of membrane-bound enzymes is critical to the understanding of cellular function and viability, and the design of membrane-based biosensing platforms. While there is a significant body of knowledge on how lipid composition and dynamics affect membrane-bound enzymes, little is known about how enzyme catalysis influences the motility and lateral transport in lipid membranes. Using enzymes-attached lipids in supported bilayers (SLB), we show catalysis-induced enhanced lateral diffusion of lipids in the bilayer. Enhancing the membrane viscosity by increasing the cholesterol content in the bilayer suppresses the overall diffusion but not the relative diffusion enhancement of the enzyme-attached lipids. We also provide direct evidence of catalysis-induced membrane fluctuations leading to the enhanced diffusion of passive tracers resting on the SLB. Additionally, by using active enzyme patches, we demonstrate the directional transport of tracers on SLBs. These are first steps in understanding diffusion and transport in lipid membranes due to active, out-of-equilibrium processes that are the hallmark of living systems. In general, our study demonstrates how active enzymes can be used to control diffusion and transport in confined 2-D environments.

An effect of antibiotic amphotericin B on ion transport across model lipid membranes and tonoplast membranes

2005 ◽  
Vol 70 (5) ◽  
pp. 668-675 ◽  
Author(s):  
Monika Hereć ◽  
Halina Dziubińska ◽  
Kazimierz Trębacz ◽  
Jacek W. Morzycki ◽  
Wiesław I. Gruszecki
Keyword(s):  
Ion Transport ◽  
Amphotericin B ◽  
Lipid Membranes ◽  
Model Lipid Membranes

scholarly journals Reversible membrane deformations by straight DNA origami filaments

Soft Matter ◽  
2021 ◽  
Author(s):  
Henri G. Franquelim ◽  
Hendrik Dietz ◽  
Petra Schwille
Keyword(s):  
Lipid Membranes ◽  
Dna Origami ◽  
Membrane Bound ◽  
Membrane Deformations

Reversible MgCl2-induced blunt-end polymerization of membrane-bound straight DNA origami monomers into filaments leads to protruding deformations on freestanding lipid membranes.

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