Digital and Tunable Genetically Encoded Tension Sensors Based on Engineered Coiled-Coils.

ABSTRACT: Genetically encoded tension sensors (GETSs) allow for quantifying forces experienced by intracellular proteins involved in mechanotransduction. The vast majority of GETSs are comprised of a FRET pair flanking an elastic "spring-like" domain that gradually extends in response to force. Because of ensemble averaging, the FRET signal generated by such analog sensors conceals forces that deviate from the average, and hence it is unknown if a subset of proteins experience greater magnitudes of force. We address this problem by developing digital GETSs comprised of coiled-coils (CCs) with tunable mechanical thresholds. We validate the mechanical response of CC digital probes using thermodynamic stability prediction, AlphaFold2 modeling, steered molecular dynamics simulations, and single-molecule

SUBMITTER: Liu S 

PROVIDER: S-EPMC12188637 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature