Year: 2025
Type: preprint
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 (β-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.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: Yale University, Research Corporation for Scientific Advancement, Deutsche Forschungsgemeinschaft, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, Office of Research Infrastructure Programs, National Institutes of Health
Awards: G1294429236, G1994913649, Molecular mechanisms of force production and force sensing during clathrin-mediated endocytosis, Untersuchung der Bildung und Instandhaltung des Membranassoziierten periodischen Zytoskelett in Neuronen eines lebenden Organismus, New strategy to measure forces at the molecular scale in vivo, Programming cellular behavior by mechanical forces, G8799960063, G9000028377, Caenorhabditis Genetics Center, Kinesin Motors and Microtubule-based Trafficking, Single-molecule studies of SNARE assembly and lipid transfer
OpenAlex ID: W4406573935