Molecular Force Sensors: From Fundamental Concepts toward Applications in Cell Biology

Mechanical signals are central for the regulation of developmental, physiological, and pathological processes within biological systems. Force transduction across the cell-extracellular matrix (ECM) interface is highly crucial for regulating cell fate via mechanosensing and mechanotransduction cascades. The key molecules involved in these highly sophisticated processes have been identified in recent years. But little is still known about their interactions and in particular the molecular forces that determine these interactions. This is due to the limited availability of techniques that allow for investigating force propagation and mechanobiochemical signal conversion at the molecular level in live cells. In this progress report, currently available tools for measuring the molecular forces involved in cellular mechanosensing and mechanotransduction are summarized, specifically highlighting recent advances in the development of molecular force sensors (MFSs). MFSs convert the applied force into a fluorescence signal, allowing for a direct readout of tension with optical microscopy techniques. Moving from molecular design principles to applications of MFSs, important results are summarized, highlighting the new mechanistic information that has been obtained about mechanobiochemical processes at the cell-ECM interface. This progress report finishes with a critical discussion of current promises and limitations, providing perspectives for future research in this quickly evolving field.