Ligand Anchorage and Materials Stiffness to Modulate Cell Adhesion Signals

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Physicochemical Coes of the extracellular microenvironment aect fate decisions of living cells. We aim to modulate ligand anchorage to materials surfaces in order to dissect the highly convoluted signalling pathways of major exogenous cues in cell adhesion. Thereby we want to demonstrate the specic impact of ligand anchorage in relation to two other important cues, namely materials stiffness and ligand density in a multiparameter approach independently of each other. Ligand anchorage will be modulated from strong covalent coupling to gradually weaker non-covalent intermolecular interactions of cell adhesion ligands like fibronectin to the topmost surface of the polyacrylamide hydrogel layers as it allows to tune receptor forces of adherent cells. Ligand density is adjusted during ligand coupling to the hydrogel layers, while hydrogel stiffness can be controlled via its cross-linking density. Using such a materials platform the magnitude and time dependence of the biophysical cell response will be assessed in terms of traction force cytometry. The biophysical characterisation will be accompanied by biochemical quantification of intracellular signals, such as protein expression and phosphorylation state. The correlation of both the dissected biophysical and biochemical cell response to each other is expected to provide new insights in cell adhesion signalling and the specific impact of ligand anchorage. The results are envisioned to enable a targeted materials design of cell culture scaffolds for tissue engineering and regenerative therapies.