Addressing Cell Adhesion: Protein Patterns and Switchable Conductive Polymer Systems

Abstract

Cell adhesion to the ECM is a fundamental aspect of life and influences not only attachment but also cell proliferation and differentiation. Tissue engineering and regenerative medicine has potential to solve some of the medical challenges which an ageing population creates. Currently, the development is hampered by a lack in adaptility of cell culture substrates. An ideal cell culture substrate can provide the correct cues at the right time to steer the cells towards the desired tissue and finally provide means of gently harvesting the tissue. Here, two routes towards controlled cell adhesion will be presented – protein patterns and switchable conductive polymer systems. The influence on cell adhesion and focal adhesion development by the lateral distribution of integrin ligands at interfaces was studied using a series of different sizes of protein patterns (0.1-3µm) separated by a non-adhesive backround. The nanostructured interfaces were produced from colloidal monolayer masks followed by traditional lithographic steps. The study of vitronectin and fibronectin patterns reveals mechanistic differences in focal adhesion formation and development. By confining these adhesion proteins to sub micrometer patches key clues to the cell adhesion process are exposed. Cells at small vitronectin patterns are able to bridge several ligand patches in a single focal adhesion while they are unable to at small fibronectin patterns. This may relate to the properties of fibronectin under tension. Another central element in a truly versatile cell culture substrate is switchability. It will be demonstrated how conductive polymer graft copolymer systems can be utilized to create a surface with switchable cell adhesion properties addressable by a very mild (low voltage) stimuli. An appropriate parallel cell culture format based on PDMS wells have been developed and results from cells adhering to oxidized and reduced forms of conducting polymers formed from novel ATRP (Atom Transfer Radical Polymerization) site bearing monomers will be presented. Initial studies of surfaces with grafted block co-polymers from these conducting polymer backbones have focused on polystyrene and poly acrylic acid. Switching by application of a potential leads to changes in surface properties such as morphology and contact angles.