ENGINEERING PATTERNED SURFACES TO CONTROL CELL BEHAVIOUR

This thesis was inspired by the observation that cells in their native microenvironment are constantly exposed to biophysical signals. Therefore, the effects of such signals, in particular topographic signals, on various aspects of cell behavior are presented. In order to study cell response to material mechanical properties we produced smooth hydrogel surfaces displaying locally varied elasticity regions using FIMIC (Fill-Molding In Capillaries) technique. Cells strongly react to the design on the surface, accumulating and migrating preferentially on the stiffer regions of the hydrogel in a highly selective manner. The regulation of cell behaviour via focal adhesion maturation and polarization was investigated with the use of nanograted PDMS substrates. We found that nanotopography is highly effective in altering Focal Adhesion (FA) dynamics and assembly, which eventually affects cytoskeleton spatial arrangement. Furthermore, our data show that nanograted PDMS may have a direct effect on nuclear squeezing, by inducing specific cytoskeletal assemblies and possibly modifying the intracellular stress state. Therefore, topographic signals might be effective in altering cell fate through the FAs-cytoskeleton-nucleus axis. The preliminary results here reported, showed that nanopatterned substrates resulted effective also in controlling ECM microcostituent spatial arrangement via cell migratory behavior, i.e. the topographic signals is broadcasted also to the cell secreted matrix up to a certain distance from the pattern itself. The results presented in this thesis highlight the possibility to use biophysical patterns to affect different aspects of cell behavior, such as adhesion, polarization, nuclear shape which eventually might dictate to the cell diverse cell fates. The presentation of mechanical and topographical signal on material surface represents a tool not only to analyze or alter cell behavior in and in vitro setting, but also it gives the opportunity to realize in vitro or in vivo functional tissues having microstructural features predefined ab initio.