A major challenge in the mechanobiology field stems from the lack of methods to identify mechanically active receptors, associated proteins, and the individual cells that display enhanced force generation. For instance, potent T cell activation requires the transmission of forces between the T cell receptor (TCR) and its peptide-loaded major histocompatibility complex (pMHC) antigens. TCR-antigen interactions are highly dynamic, displaying a broad range of force magnitudes between different cells and even within the same cell. Hence, methods that can install a tag on the mechanically active T cells, TCRs, and their associated proteomes, or mechanomes are highly desirable. Such techniques may enable a deeper understanding of the mechanisms governing immune responses and may also have broad applications in immunotherapy. Herein, we report a technique dubbed mechano-ID, which allows for mechanically selective proximity tagging by leveraging DNA-based molecular force probes that recruit proximity-tagging enzymes. We demonstrate mechano-ID with naïve OT-1 T cells using microscopy and flow cytometry, with further confirmation by proteomics and western blotting of mechanically active TCRs.
Rahman et al. (Sun,) studied this question.
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