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Genetically encoded mechano-sensors with versatile readouts and compact size

Ren, Y.; Yang, J.; Saito, T.; Glomb, O.; Mousavi, S. I.; Naughton, B.; de Fontnouvelle, C.; Fujita, B.; Schlieker, C.; Yogev, S.; Zhang, Y.; Berro, J.

2025-01-18 cell biology
10.1101/2025.01.16.633409 bioRxiv
Show abstract

Mechanical forces are critical for virtually all fundamental biological processes, yet quantification of mechanical forces at the molecular scale in vivo remains challenging. Here, we present a new strategy using calibrated coiled coils as genetically encoded, compact, tunable, and modular mechano-sensors to substantially simplify force measurement in vivo, via diverse readouts (luminescence, fluorescence and analytical biochemistry) and instrumentation readily available in biology labs. We demonstrate the broad applicability and ease-of-use of these coiled coil mechano-sensors by measuring forces during cytokinesis (formin Cdc12) and endocytosis (epsin Ent1) in yeast, force distributions in nematode axons ({beta}-spectrin UNC-70), and forces transmitted to the nucleus (mini-nesprin-2G) and within focal adhesions (vinculin) in mammalian cells. We report discoveries in intracellular force transmission that have been elusive to existing tools.

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