Adhesion is a key event for eukaryotic cells to establish contact with the extracellular matrix and other cells. It allows cells to quickly adapt to mechanical changes in their environment by either adhesion reinforcement or release. Understanding and mimicking the interplay between adhesion reinforcement and release could result in novel cell-inspired adaptive materials. In order to ultimately be able to transfer functional principles of cell adhesion to a next generation of biomimetic materials, we will elucidate the biophysics of cell adhesion in response to external force. We have already obtained important results that have provided new insights into cell adhesion. For example, we have found that the nanoscale spacing of adhesion sites controls cell adhesion reinforcement. With the project proposed here I want to advance our understanding of cell adhesion by generating a comprehensive model of mechanotransduction-mediated cell adhesion. Therefore, my group will develop new force measurement methods based on atomic force microscopy and 2D force sensor arrays that allow for a systematic investigation of key parameters in the cell adhesion system, including the concept of cellular mechanosensing. My hypothesis is that there is a transition between adhesion reinforcement and release as a function of external mechanical stress, stress history, and the biofunctionalization of the adhesive surface. Transferring our biophysical knowledge into materials science promises new materials with a dynamic adaptive mechanical and adhesion response. This transfer of biological concepts into cell-inspired materials will follow the construction principles of cells: the proposed material will be based on polymer fibers that are reversibly cross-linked and reinforce adhesion upon mechanical stress. The ultimate goal of the proposed project is to develop an intelligent polymer material with an adaptive adhesive and mechanical response similar to that found in living cells.