Cell-substrate interactions have a pronounced effect on cell attachment, growth and proliferation in healthy tissues and disease. The complexity of the in vivo setting has fueled in vitro studies on different aspects of cell behavior in response to different material properties. The proposed research project aims at establishing links between substrate properties and the fundamental process of endocytosis, on which limited knowledge currently exists. The use of mechanically and chemically defined, nano-patterned surfaces to probe the cellular mechanisms of regulation of different internalization pathways will be achieved through use of specialized cargoes, fluorescent labeling and imaging techniques. Strong emphasis will be placed on cancer cells, where both derailed endocytosis and abnormal extracellular matrix contribute to the disease. The combination of the researcher’s strong background on endocytosis of nano structures and the host laboratory’s expertise on surface fabrication and cell-surface interactions guarantee implementation of the project. The anticipated results will have a pronounced impact on our understanding of this fundamental cell process and are likely to be of technological interest in the fields of drug delivery and tissue engineering in the near future.