How the stretching of extracellular matrix proteins affects cell signaling

• Applicant: Dr. Ingmar Schön
• Subject Area: Biophysics
• Term: from 2009 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 113192526

Fibronectin (FN) is an integral component of the extracellular matrix (ECM). It is organized into fibrils that are linked to the cytoskeleton via integrins. Binding sites for a variety of molecules are buried in the fold of FN and can be mechanically activated (unraveled) by fibril stretching. Also integrins must undergo a conformational transition into an “activated” state in order to bind to FN. The proposed research project aims at improving our understanding of how these conformational changes are translated into biochemical and electrical signals in the cell, respectively. In a first set of experiments, we want to determine the order by which FN fibrils expose specific binding sites for growth factors or other ECM proteins sequentially with increasing strain. We therefore will employ stretching of in vitro fabricated fibrils and detection of fluorescently labeled proteins in various combinations. As the binding to FN often triggers intracellular signaling cascades, the results of this study will help to explain how a cell is able to distinguish between, and react to mechanical stimuli of different strength. The second part addresses the functional regulation of ion channels by integrin-mediated adhesion processes. Electrophysiological recordings with fibroblasts adhering to substrates of different stiffness will be conducted in order to characterize the electrical response of the cell, to identify target channels, and to elucidate the intermediate steps of this crosstalk. Overall, our study will advance the understanding of developmental processes and tissue repair and has practical applications in tissue engineering and the design of functional materials with tailor-made elastic properties.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professorin Dr. Viola Vogel