The Piconewton Force Awakens: Quantifying Mechanics in Cells

The development of calibrated Förster resonance energy transfer (FRET)-based tension sensors has allowed the first analyses of mechanical processes with piconewton (pN) sensitivity in cells. Here, we introduce the working principle of this emerging microscopy method and discuss how it has been utilized to obtain quantitative insights into the mechanisms of intracellular force transduction in cell-matrix adhesions, cell-cell junctions, and at the cell cortex. These examples demonstrate that genetically encoded tension sensors are powerful tools to unravel force transduction mechanisms, but also indicate current limitations. We propose that further technical improvements are needed to develop a truly molecular understanding of mechanobiological processes in cells and tissues.