Publications [#294002] of Ron Grunwald

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Papers Published

  1. Grunwald, R; Painter, GR, The effects of lipid composition on the binding of lasalocid A to small unilamellar vesicles., Biochimica et biophysica acta, vol. 1027 no. 3 (September, 1990), pp. 245-252 [doi] .
    (last updated on 2024/04/23)

    Abstract:
    The binding of the carboxylic ionophore lasalocid A (X537A) to small unilamellar phospholipid vesicles of varying composition was examined in an effort to determine what structural features of the phospholipid membrane influence the ionophore-membrane interaction. Apparent dissociation constants (Kapp) were calculated for both the acidic and anionic forms of the ionophore using the change in fluorescence intensity observed for lasalocid A upon addition of phospholipid vesicles. The Kapp for binding to fluid phase dimyristoylphosphatidylcholine (DMPC) vesicles is 46 microM for the anion and 14 microM for the acid. While the phase transition of DMPC had no effect on the Kapp of the anion, an increase was observed in the Kapp of the acid below the phase transition temperature. The Kapp of the anion was not affected by the incorporation of 10% dimyristoylphosphatidylethanolamine (DMPE), but increased slightly upon incorporation of cholesterol. The pKa values of the ionophore were the same in DMPC and DMPC/DMPE membranes. Incorporation of the negative lipids phosphatidylglycerol, phosphatidic acid, or phosphatidylethanolamine (at pH 9.4 where PE carries a negative charge) decreases binding of the anion in accord with the increase in surface potential estimated from Gouy-Chapman theory. The CD spectrum of membrane-bound lasalocid A anion indicated the ionophore to be in an extended acyclic conformation on the membrane surface with the C-1 carboxylate rotated out of the plane of the salicylate ring. The out-of-plane rotation of the carboxylate may be the result of facial binding by the amphiphilic ionophore on the membrane surface or of weak ion pairing to the polar lipid head groups. These results suggest that the primary determinants of binding of the anionic ionophore on the membrane surface are packing density of the polar head groups and membrane surface potential. There is no evidence of strong hydrogen bond formation between the lipid polar head groups and the ionophore as has previously been suggested.