Nitroxide spin-probe study of amphotericin B – ergosterol interaction in egg phosphatidylcholine multilayers

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Abstract
The interaction between the polyene macrolide antibiotic, amphotericin B and ergosterol in egg phosphatidylcholine multilayers was investigated using head group and acyl chain nitroxide spin-labeled phosphatidylcholine as probes. At physiological concentrations of less than 15 mol% sterol in egg phosphatidylcholine multilayers amphotericin B accumulates near the head group region until an amphotericin B:ergosterol ratio of approximately 0.7 is achieved. As the proportion of amphotericin B is increased above this value, formation of an acyl chain disordering complex occurs which has an approximate antibiotic:sterol ratio of unity. Dicetyl phosphate was used to increase the solubility of ergosterol past its normal limit in pure egg phosphatidylcholine (.apprx. 15 mol%). At concentrations of ergosterol higher than 15 mol% a complex of 2 ergosterol molecules and 1 amphotericin B was postulated when there was insufficient antibiotic to form a 1:1 complex.