FIGURE 4.

Examples of applying mechanobiology for immuno-engineering. (A) Examples of SynNotch based mechanosensing molecular modulators. Antigen specific synthetic notch receptors were tagged with a transcription factor (TF) intracellularly. Its activation can lead to gene expression upon antigen binding, via the subsequence release of TF upon cleavage (left). An apelin based SynNotch receptor tethered to a Cre or tTA recombinase intracellularly. Upon apelin-APJ interaction, the cleavage will release the recombinase and activate the designed gene of interest (right). (B) Schematic showing of ultrasound activation of engineered immune cells, Ultrasound can activate mechanosensitive ion channel expressing T cell and trigger gene activation through designed genetic circuits to specifically kill antigen expressing tumor cells (left). Macrophages were engineered with ultrasound-responsive components and the payload. Upon short-pulsed high intensity focused ultrasound (HIFU) sonication, the macrophages can be disrupted, which allows drug release into the tumor locus (right).