The two-party research consortium has systematically studied the cytotoxic profile of organic (latex) and inorganic (silica) nanoparticles in contact to epithelial cells by means of impedance analysis and more classical cytotoxicity assays. The effect of NP surface charge was studied by using polystyrene (PS) beads with different surface functionalities (amino versus carboxy) whereas silica beads of different size were used as an unmodified reference material. All experimental indicators revealed equivocally that positive charges on the NP surface provide better uptake, but also more severe toxicity and as a consequence the inability of the cells to close experimental wounds. In contrast, negatively charged PS-NPs and silica NPs without surface modifications did not show a considerable toxicity independent of particle size on time scales from minutes to seven days. However, even for these rather inert NPs we did observe slight indications for an NP impact on more sensible cell functions like cell migration and wound healing. Thus, this project aims to focus on the impact of stable NPs on more sensitive and supposedly more vulnerable cellular processes like (i) cell proliferation, (ii) cell differentiation, (iii) cell communication and (iv) different highly specialized, cell-type specific physiologic activities (myocyte contraction, epithelial transport). For the different parts of the project we will make use of appropriate cell culture models in combination with commercial NPs made from PS and silica that are known to be chemically stable in suspension. It is the main idea to unravel the potential hazards for vulnerable biological functionalities arising from small scale particles at doses that are not sufficient to induce obvious cytotoxicity. We will study NP impact on the above mentioned key events of cell physiology upon extracellular exposure and also after introduction of the free particles into the cytoplasm by membrane electroporation.
