Dr. Nico Strohmeyer
ETH Zürich/D-BSSE

jointly organized with SFB1032

In tissues, cells employ integrin-mediated adhesion sites to sense the biophysical and biochemical properties of and adhere to fibrillar extracellular matrices (ECM), which is essential for physiological cell function, organ morphogenesis, and tissue homeostasis. Non-physiological properties of ECMs or their misinterpretation by cells have serious consequences, such as carcinogenesis and fibrosis. Integrin-mediated adhesion sites are complex supramolecular structures that develop from a few integrins that initiate the process of adhesion formation and recruit a variety of auxiliary proteins to form a sophisticated and highly dynamic signaling platform. While the process of adhesion initiation is essential for the formation of physiological cell adhesion and signal transduction, the molecular details of how cells initially interact with ECM proteins to establish adhesion and how the biochemical and biophysical properties of these materials affect cellular signaling are still elusive. To unravel biophysical and biochemical principles of adhesion formation, we use atomic force microscopy-based single-cell force spectroscopy to quantify how fibroblasts employ integrins to recognize fibronectin and adjust their adhesion characteristics in response to their environment. I will describe molecular properties of integrins and fibronectin that regulate cell adhesion initiation and strengthening and will show how the dynamics of integrin ligand binding and adhesion formation dynamics can be controlled by G protein-coupled receptor signaling. To illustrate the complexity of adhesion initiation, I will discuss how different fibronectin-binding integrins utilize intracellular signaling cascades to synergize in strengthening cell adhesion. Further, I will demonstrate how integrins sense the mechanical information of the environment by an immediate response to mechanical signals from the environment while establishing adhesion and describe how fibroblasts regulate adhesion in response to fibrillarity and stiffness of the fibronectin. Finally, I will discuss how integrins are rewired during cell separation from cell-ECM adhesion to strengthen cell-cell adhesion. The results discussed show how integrins coordinate adhesion initiation with various signaling pathways and their biological significance.