The chronic consumption of fumonisin B1 (FB1), a common cereal contaminant fungal toxin, is correlated with hepatic and esophageal cancers, and neural tube defects. The inhibition of ceramide synthase, and the resultant disruption of sphingolipids metabolism, is believed to be its main toxicity mechanism. However, there is some evidence that the toxicity of this compound is not solely due to this enzymatic inhibition. A direct interaction FB1-biomembranes could be also involved in the early stages of FB1 toxicity. Hence, in this work we evaluated the possible formation of FB1 self-assembly structures, and characterized some FB1-membranes interactions. The critical micellar concentration of FB1 was 1.97 mM, determined by the changes in the absorbance of the hydrophobic dye bromothymol blue. On the other hand, the FB1 ability to interact with organized lipids was measured by the toxin penetration in monomolecular layers at the air-water interface at different monolayer composition and molecular packing, mycotoxin concentration in the subphase, as well as subphase pH. FB1 (5.6 µM) increased the lateral surface pressure (π) in the following order: dpPC:DOTAP 3:1>dpPC:dpPA 3:1>dpPC. In the absence of monolayer, the toxin stabilized itself in a free air-water interface, but the monolayer so formed with FB1 did not remain stable after compression. This mycotoxin (0-79.82 µM) increased linearly the π values of EPC monolayers (πi ≈ 10 mN/m). Moreover, the maximal π allowing the drug penetration (πcut-off) were πcut-off = 34.3 and 27.7 mN/m at pH=7.4 and 2.63, respectively. The possible disturbances in the membrane environment due to the incorporation of FB1 to MLVs were studied using DPH and TMA-DPH as probes. FB1 (0-81.4 µM) linearly decreased the anisotropy of TMA-DPH fluorescence (from 0.349±0.003 to 0.1720±0.0035), whilst no differences were registered when DPH was used, strongly indicating the interfacial location of FB1. Depending on the surface electrostatic properties, the interfacial FB1-membrane interaction would involve a different folding type of FB1 (reported in molecular mechanics and dynamics simulation studies). These results support the lipid-mediated hypothesis of FBI toxicity in human and animal cells. π) in the following order: dpPC:DOTAP 3:1>dpPC:dpPA 3:1>dpPC. In the absence of monolayer, the toxin stabilized itself in a free air-water interface, but the monolayer so formed with FB1 did not remain stable after compression. This mycotoxin (0-79.82 µM) increased linearly the π values of EPC monolayers (πi ≈ 10 mN/m). Moreover, the maximal π allowing the drug penetration (πcut-off) were πcut-off = 34.3 and 27.7 mN/m at pH=7.4 and 2.63, respectively. The possible disturbances in the membrane environment due to the incorporation of FB1 to MLVs were studied using DPH and TMA-DPH as probes. FB1 (0-81.4 µM) linearly decreased the anisotropy of TMA-DPH fluorescence (from 0.349±0.003 to 0.1720±0.0035), whilst no differences were registered when DPH was used, strongly indicating the interfacial location of FB1. Depending on the surface electrostatic properties, the interfacial FB1-membrane interaction would involve a different folding type of FB1 (reported in molecular mechanics and dynamics simulation studies). These results support the lipid-mediated hypothesis of FBI toxicity in human and animal cells.
