Cellular uptake of nanoparticles by membrane penetration: a study combining confocal microscopy with FTIR spectroelectrochemistry.

It is well-known that nanomaterials are capable of entering living cells, often by utilizing the cells' endocytic mechanisms. Passive penetration of the lipid bilayer may, however, occur as an alternative process. Here we have focused on the passive transport of small nanoparticles across the plasma membranes of red blood cells, which are incapable of endocytosis. By using fluorescence microscopy, we have observed that zwitterionic quantum dots penetrate through the cell membranes so that they can be found inside the cells. The penetration-induced structural changes of the lipid bilayer were explored by surface-enhanced infrared absorption spectroscopy and electrochemistry studies of model membranes prepared on solid supports with lipid compositions identical to those of red blood cell membranes. A detailed analysis of the infrared spectra revealed a markedly enhanced flexibility of the lipid bilayers in the presence of nanoparticles. The electrochemistry data showed that the overall membrane structure remained intact; however, no persistent holes were formed in the bilayers.