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

Martín G Theumer1, Eduardo M Clop, Héctor R Rubinstein

  • 1Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.

Insights

Fumonisin B1 (FB1) disrupts biomembrane organization by altering lipid packing and surface properties. These molecular changes in lipid metabolism are key to understanding FB1 mycotoxicity.

Area of Science:

  • Biochemistry
  • Biophysics
  • Toxicology

Background:

  • Fumonisin B1 (FB1) is a mycotoxin whose toxic mechanisms are not fully understood.
  • Disruption of lipid metabolism is a potential pathway for FB1 toxicity.
  • Investigating FB1's interaction with biomembranes can elucidate its toxic effects.

Purpose of the Study:

  • To investigate the molecular organizational changes induced by FB1-biomembrane interactions.
  • To understand the role of these changes in FB1-induced mycotoxic effects.

Main Methods:

  • FB1 self-aggregation and critical micellar concentration determination.
  • Fluorescence anisotropy measurements using TMA-DPH and DPH probes in lipid bilayers.
  • Langmuir film analysis to assess changes in lateral surface pressure and surface potential.
  • Monolayer composition, molecular packing, and pH-dependent effects were evaluated.

Main Results:

  • FB1 self-aggregates with a critical micellar concentration of 1.97 mM.
  • FB1 dose-dependently decreased fluorescence anisotropy in dpPC bilayers, indicating altered lipid dynamics.
  • FB1 increased lateral surface pressure and altered surface potential of lipid monolayers, with effects dependent on monolayer composition, packing, and pH.
  • FB1-lipid interactions induced long-range effects on lipid domain organization.

Conclusions:

  • FB1 interacts with biomembranes, inducing significant molecular organizational changes.
  • These changes in lipid metabolism and membrane structure are likely involved in FB1's mycotoxic mechanisms.
  • FB1's interaction and orientation are influenced by membrane electrostatics and its own charge state.

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