Analyzing intracellular force transduction using novel biosensors

Cells are frequently subject to mechanical forces. Skin cells, for instance, are exposed to forces from shear, pressure or stretch whereas cells in the blood vessels are subject to the shear forces of the blood flow; cells in our lungs feel forces from inflation while cells in the heart sense the rhythmic contractions of the heartbeat. In addition cells also generate their own intracellular forces as is obvious during cell division or cell migration.

The ability of cells to integrate these kinds of mechanical information is central to a wide range of biological processes and has important implications for diseases such as arteriosclerosis, muscular dystrophies or cancer. The molecular mechanisms that underlie cells’ mechanosensitivity, however, are largely elusive. The reason for our limited understanding has been the lack of suitable methods to study force propagation on the sub-cellular level in living cells.

We have developed a light microscopy-based method that uses ‘Förster resonance energy transfer (FRET)’ to visualize and quantify mechanical forces within cells. The technique allows us to study mechanisms of force transduction on the molecular level, with high sensitivity and spatio-temporal resolution. It has been successfully used to determine mechanical forces across the cell adhesion protein vinculin and is currently applied to other proteins.