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Engineered nanoparticles of < 20 nm have the potential for several direct biophysical interactions with nanoscale membrane proteins and the lipid bilayer of cells. Indeed all downstream nanoparticle effects must initiate with some kind of membrane interaction whether it be membrane penetrance or modification of membrane function. We have examined these interactions in detail using the patch/ voltage clamp technique, and superresolution imaging which allow very fast < 10 ms events to be resolved. In screening a large number of nanoparticle species (Ag, ZnO, SiO2, TiO2 MgO). We have revealed two unique interactions at the membrane level: 1) the nano-pore forming ability of Ag which may partly explain its toxicity, and 2) a unique membrane protein-nano interaction of ZnO. We will conclude that a better understanding of membrane -nanoparticle biophysical interactions will open opportunities for the use of nanoparticles as novel tools in membrane biology and bioengineering.