The widely used explosive, 2,4,6-trinitrotoluene (TNT), is a highly toxic chemical, which can cause hepatitis, cataracts, jaundice and so on, in humans. The interaction between TNT and biological membranes is crucial for understanding its toxic effects. Here, we mainly focused on molecular-level mechanisms for the collective adsorption of TNT into lipid membranes and the corresponding effects on bilayer properties by all-atom molecular dynamics simulations. We revealed that TNT can readily form an aggregate in the aqueous phase and quickly approach the surface of the membrane. At low concentrations of TNT (7 mol%), the aggregate is unstable and breaks up after several nanoseconds, and then the dispersed TNT molecules enter the membrane alone. At high concentrations (14 mol%), the aggregate is adsorbed as a whole and remains stable inside the membrane. After some of the TNT is absorbed by the membrane, the remaining TNT across the membrane would have greater permeability, i.e., the calculated permeability coefficient (P) is increased from 1.7 × 10−2 to 18.3 cm s−1. Correspondingly, a higher bioconcentration factor (BCF) was also observed. The increased level is more pronounced in the presence of TNT aggregates (i.e., high concentrations). This phenomenon is closely related to the strong interaction between TNT molecules. The results suggested that TNT molecules that have entered into the membrane can facilitate the membrane uptake, permeation and bioaccumulation of subsequent TNT molecules, exhibiting a synergistic effect. This work has a certain significance for understanding the toxicity of TNT.
