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Designing nanoadhesive keys to manipulate cell adhesion and signalling

Final Activity Report Summary - CELLADHESIVENANOKEYS (Designing nanoadhesive keys to manipulate cell adhesion and signalling)

Animal cells, whose dimensions are in the range of several tens of micrometers, perceive and react to chemical, structural and mechanical signals that are spatially distributed on the nanometre and micrometre scales. Therefore, a man-made substrate whose chemical composition and structural features are perfectly controlled down to the nanometre range is an ideal tool to regulate cell behaviour. In this area nanotechnology advances can give a helping hand.

A novel nanolithography technique which allowed for the creation of periodical nanopatterns of biochemical signals that were perceptible by cells was recently developed at the University of Heidelberg (Arnold et al, 2004, Chemphyschem). By appropriately choosing the identity of the chemical signals and the way in which they were spatially distributed, surfaces produced using this technique could be used to switch on and off targeted cell functions. This new technology provided ways to design materials that were able to influence cell behaviour.

In the present project, our aim was to further explore the potential offered by this new nanotechnology platform in the field of cell biology. More specifically, we focussed on the study of the clustering of Epidermal growth factor (EGF) receptors at cell surfaces in order to bring new insights into the mechanism of action of those receptors. We wanted to determine whether a specific interdistance between two EGF receptors was required for activation and if changes in receptor interdistances could influence the biological effects of EGF on cells. Ultimately, our aim was also to develop substrates nanopatterned with chemical signals that could sustain cells in culture in the absence of animal serum.

Serum is routinely added to cell cultures as a source of nutrients; however its use has significant disadvantages, including contamination risks which compromise the use of in vitro cultured cells for clinical purposes. Thus, removing the need to use serum would greatly benefit fields such as stem cell research and tissue engineering. Our results showed that cells responded to structural differences in EGF nanopatterns and that the bio-active surfaces developed using the novel nanotechnology platform were able to influence cell growth. The results obtained using nanopatterns of EGF constituted an important step in the experimental plan for generating substrates to culture cells in serum-free conditions, and further significant advancements were at reach by the time of the project completion.