The lipid-mediated hypothesis of fumonisin B1 toxicodynamics tested in model membranes.

MARTÍN G. THEUMER; EDUARDO M. CLOP; HÉCTOR R. RUBINSTEIN; MARÍA A. PERILLO

COLLOIDS AND SURFACES B-BIOINTERFACES

Elsevier

Lugar: Amsterdam, The Netherlands; Año: 2008 vol. 64 p. 22 - 33

0927-7765

Abstract The disruption of lipidic metabolism was considered a good candidate to explain FB1 toxicity mechanism. In the present work we investigated molecular organizational changes induced by FB1?biomembrane interaction possibly involved in mycotoxic effects. FB1 was self-aggregated with a critical micellar concentration of 1.97 mM. FB1 (0?81.4 ìM), decreased in a dose-dependent manner, the fluorescence anisotropy of TMA-DPH (from 0.349 ± 0.003 to 0.1720 ± 0.0035) in dpPC bilayers, whilst no differences were registered with DPH. At 5.6 ìM in the subphase, FB1 increased the lateral surface pressure (ð) of a Langmuir film to an extent that depended on the monolayer composition (ÄðdpPC:DOTAP 3:1 > ÄðdpPC:dpPA3:1 > ÄðdpPC), the molecular packing (Äð decreased linearly as a function of the initial ð) and the subphase pH (ÄðpH 2.6 > ÄðpH 7.4 and maximal ð allowing the drug penetration ðcut-off was 34.3 and 27.7 mN/m at pH 2.63 and 7.4, respectively). FB1 increased the surface potential of dpPC and dpPC:DOTAP monolayers and decreased that of dpPC:dpPA. This suggested that FB1 acquired different orientations and/or foldings depending on the surface electrostatics and the toxin charge state. Moreover, FB1?lipid interactions were transduced into long-range effects at the mesoscopic level affecting the lipidic self-separated lateral domains shape and density.