Interaction of nanoparticles with cellular compartments and proteins

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Sets of polymeric nanoparticles of defined parameters concerning size, type of polymer and surface functionality containing a fluorescent marker will be synthesized and characterized. With advanced fluorescence microscopy techniques, we will explore in detail the uptake mechanisms by the cell and their dependencies on the physical properties of the nanoparticle (size, shape) and its surface chemistry (chemical functions, charge and polarity). We will analyze in detail how nanoparticles are processed within the cell (transport mechanisms, association with organelles, degradation), and responses of the cell to nanoparticle incorporation. These studies will be done by using time-resolved spinning disk confocal microscopy on cultured cells provided by the Mailänder/Simmet groups, complemented by 4Pi-confocal experiments and STED microscopy with ultra-high spatial resolution on living cells. With these experiments, we aim to achieve a mechanistic description, in molecular terms, of the response of cultured cells to nanoparticles, which is a first important step towards an understanding of the effects of nanoparticles on the entire organism. Phagocytosing monocytic cells are pivotal for inflammation and host defence. Accordingly, they are equipped with binding proteins and receptors that allow efficient sensing and internalization of nanoparticles. On this background it is very important to gain insight not only in i) the interaction between distinctly designed nanoparticles with differentiated primary cells and dedifferentiates tumor cells, but also ii) to identify possible receptors and target molecules, iii) to develop mathematical models describing the interaction between nanoparticles and the cells, and iv) to identify cell functions that may be targeted by nanoparticles.