Pawlak, M. R.; Baldys, A.; McMahon, M. C.; Cichocki, F.; Gordon, W. R.

In this work, we establish a general high-throughput molecular tension sensor platform compatible with diverse ligands, cell lines and therapeutic targets. We demonstrate strategies to mitigate nuclease degradation and introduce a novel method for covalently linking IgG-containing proteins to DNA structures using engineered Protein G28 (PG)-HUH fusion. These advancements are not limited to integrins but provide a broadly applicable strategy for studying mechanotransduction across multiple receptor types. By integrating these developments into RAD-TGTs, we provide a robust screening platform for mechanotherapeutics which can be used to profile how these treatments alter a cell\'s mechanical phenotype (mechanotype) . We demonstrate this function by analyzing the effect of integrin modulatory agents in both immortalized cell lines and primary immune cells.This work lays the foundation for expanding MTS applications beyond specialized mechanobiology labs, making them accessible for broader use in drug development and mechanomedicine.