Research Group "Molecular Mechanotransduction" (Carsten Grashoff)
The cells of our body are exposed to a wide range of mechanical forces and they are continuously compressed, sheared or stretched. Cells can respond to these mechanical stimulations, but is unknown how forces are processed, because suitable methods to measure forces within cells are missing. Carsten Grashoff and his research group are therefore developing microscopy methods to measure mechanical forces across intracellular proteins in cells. As a tool they use highly elastic proteins such as the spider silk protein flagelliform, which can be stretched by very little forces. The scientists combine the characteristics of such elastic proteins with a physical effect called FRET (Förster Resonance Energy Transfer), which can occur between two fluorescent molecules and depends on their separation distance. Are the fluorophores linked by elastic proteins that stretch in response to mechanical tension – and thereby increase the separation distance between the fluorescent molecules – forces can be determined by FRET measurements. The first successful application of this novel technique targeted the adhesion protein vinculin, which is located at the plasma membrane of cells and important for surface adhesion during cell migration. As shown here, areas of high vinculin forces (indicated in blue/green) can be distinguished from regions where tension across vinculin is rather low (yellow/red). Such experiments allow for the analysis of force propagation mechanisms in living cells.