WHaloForce enables chemigenetic imaging of molecular tension in living cells and animals

WHaloForce, a chemigenetic HaloTag tension sensor, shows a switch-like dye unquenching transition near 5 pN and enables quantitative molecular tension imaging in living cells and animals.

• Why it matters: Piconewton-scale forces within protein assemblies are important for adhesion and morphogenesis but are hard to measure dynamically in living systems.
• What they did: The sensor uses force-dependent relief of tryptophan-mediated dye quenching to produce fluorescence lifetime changes, validated with optical tweezers and applied to endogenous expression in mammalian cells, mouse tissue, and Caenorhabditis elegans.
• The result: It reports tension in vinculin, E-cadherin, -catenin, and laminin, reveals opposite tissue-specific tension patterns in C. elegans, and identifies ovulation as a source of loading in the spermathecal laminin network.

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