Molecular tension sensors are used to measure the forces sensed by mechanosensitive proteins. (A) Models of the different types of molecular tension sensors (MTSs). A typical MTS is composed of a FRET pair (or fluorophore-quencher pair) connected by a spring-like linker that can be extended by force. Three types of MTSs have been invented: the peptide-based MTS uses engineered tension-sensitive peptide as the linker and can be genetically encoded into intracellular proteins, the DNA-based digital MTS unwinds its hairpin structure and changes fluorescence intensity when force is above a defined threshold and is used to determine the lower limits of mechanical stress, and the DNA-based rupturable MTS is irreversibly ruptured by forces above defined thresholds and is used to approach the upper limits of forces transmitted by cell surface receptors. (B) Limitation of the bulk measurement in an MTS experiment. Because of the spatial resolution, current MTS measurements calculate forces as the mean mechanical stress of all MTS probes within each pixel. Such a measurement is strongly influenced by the background of unengaged MTS probes and the variation of forces sensed by each individual MTS probe.