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

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.

• Publication year

  1970

• Venue

  The Journal of General Physiology

• Publication date

  1970-03-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1085/JGP.55.3.375PMID 4938534PMCID 2203000
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Amphotericin B produced similar permeability changes in phospholipid-free sterol membranes, but not in membranes lacking cholesterol or containing sterol analogs.

  Confidence 0.94

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• N-acetylamphotericin B and its methyl ester produced permeability changes comparable to amphotericin B, whereas small-ring polyenes did not.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• Amphotericin B increased permeability to hydrophilic nonelectrolytes and accelerated osmotic water flow.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• At 10^-6 M, amphotericin B lowered DC resistance in thin lipid membranes and converted them from Na+-selective to Cl--selective.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review

• amphotericin b

  compound

  A polyene antifungal compound used here as the membrane-active agent.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• chloride selectivity

  property

  Preference of the membrane for anion transport over cation transport.

  Aliases: Cl- selectivity, anion selectivity

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• cholesterol

  sterol

  The sterol added to phospholipid-containing membrane-forming solutions.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• hydrophilic nonelectrolytes

  solute

  Uncharged water-soluble solutes used to probe membrane permeability.

  Aliases: nonelectrolytes

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• membrane resistance

  measurement

  Electrical resistance of the membrane measured as DC resistance.

  Aliases: DC membrane resistance

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• methyl ester of n-acetylamphotericin b

  compound

  A methyl-ester derivative of N-acetylamphotericin B tested as a related amphotericin analog.

  Aliases: N-acetylamphotericin B methyl ester

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• n-acetylamphotericin b

  compound

  An acetylated derivative of amphotericin B tested alongside the parent compound.

  Aliases: N-acetyl amphotericin B

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• osmotic water flow

  process

  Water movement across the membrane measured during osmotic experiments.

  Aliases: water flow during osmosis

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• phospholipid-free sterol membranes

  membrane system

  Artificial membranes made from sterol solutions without phospholipid.

  Aliases: sterol membranes

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• small-ring polyenes

  compound group

  Comparative polyene compounds with smaller ring systems that were tested alongside amphotericin B derivatives.

  Aliases: filipin, rimocidin, PA-166

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• sterol analogs

  sterol group

  Cholesterol substitutes tested in the membrane preparations.

  Aliases: cholesterol palmitate, dihydrotachysterol, epicholesterol, Delta5-cholesten-3-one

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review
• thin lipid membranes

  membrane system

  Artificial bilayers formed from sheep red cell phospholipids and cholesterol for permeability measurements.

  Aliases: lipid membranes

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) review

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