Membrane perturbation of fullerene and graphene oxide distinguished by pore-forming peptide melittin

Abstract Carbon nanomaterials such as fullerenes (C60) and graphene oxide (GO) are considered as promising candidates for diverse applications in biotechnology and biomedicine. However, their potential toxic effects are still under debate. Herein, by using melittin (Mel), a representative pore-forming peptide, as a testing molecule we demonstrated that even the low-concentrated (usually assumed non-toxic) C60 and GO could still mechanically perturb a cell membrane by adsorption and insertion, and consequently influence the function realization of membrane active proteins/peptides. Such perturbations, however, are particle-property and membrane-environment dependent. GO would sensitize both model bilayers and bacterial membranes to Mel, demonstrated as significantly enhanced membrane permeabilization ability or improved antibacterial performance of Mel. In contrast, C60 activates the permeabilization effect of Mel on model membranes, while produces exactly the reverse effect on living bacteria and mammalian cells. Simulations further provide molecular details of the structural disturbance and probe the residue-specific formation of C60-Mel complex in membrane. This work emphasizes the dependence of biological toxicity of nanomaterials on their physico-chemical properties, provides a facile method to detect the subtle structural perturbation of cell membranes at nanoscale, and suggests a necessity for a careful evaluation of the potential influences of nanomaterials on biological processes.