Electrophysiological characterization of membrane disruption by nanoparticles

Direct contact of nanoparticles with the plasma membrane is essential for biomedical applications such as intracellular drug delivery and imaging, but the effect of nanoparticle association on membrane structure and function is largely unknown. Here we employ a sensitive electrophysiological method to assess the stability of protein-free membranes in the presence of silica nanospheres of different size and surface chemistry. It is shown that all the silica nanospheres permeabilize the lipid bilayers already at femtomolar concentrations, below reported cytotoxic values. Surprisingly, it is observed that a proportion of the nanospheres is able to translocate over the pure-lipid bilayer. Confocal fluorescence imaging of fluorescent nanosphere analogues also enables estimation of the particle density at the membrane surface; a significant increase in bilayer permeability is already apparent when less than 1% of the bilayer area is occupied by silica nanospheres. It can be envisaged that higher concentrations of nanoparticles lead to an increased surface coverage and a concomitant decrease in bilayer stability, which may contribute to the plasma membrane damage, inferred from lactate dehydrogenase release, that is regularly observed in nanotoxicity studies with cell cultures. This biophysical approach gives quantitative insight into nanosphere-bilayer interactions and suggests that nanoparticle-lipid interactions alone can compromise the barrier function of the plasma membrane.