(a) Design of mechanical inducible CAR. Piezo1 channel is coupled with microbubbles (MBs). Upon low-intensity pulsed ultrasound stimulation, Piezo1 channel opens and induces increase of cytosol calcium (Ca2+) level. NFAT, a Ca2+-dependent transcription factor, is then dephosphorylated and translocates into the nucleus, which drives CAR expression through a synthetic genetic circuit. (b) Design of heat inducible CAR by ultrasound. Focused ultrasound stimulation with relatively high-intensity generates heat in the targeted tissue. The increase of temperature is sensed by heat shock factors (HSFs), which form active trimer and drive DNA recombinase Cre expression. The subsequent excision of lox-flanked stop codon by Cre enables the expression of CAR.