Cells do not simply endure mechanical forces - they generate, transmit, and interpret them as biological signals. From membrane tension and receptor pulling to substrate stiffness and fluid shear, physical inputs shape migration, differentiation, immune function, and tissue organization. Whereas mechanobiology seeks to understand how living systems read these cues, synthetic mechanobiology treats mechanoregulatory pathways as an input-output relationship that can be deliberately programmed. Integrating tools from synthetic biology with mechanobiological principles, this emerging field reframes force-sensing as a design problem in which mechanical signaling is rewired to achieve useful outcomes - and in which the act of rewiring can itself serve as a powerful investigational strategy. Here, I survey the molecular mechanisms of mechanosensing, describe their use as modular mechanogenetic parts, and discuss applications and open challenges. The long-term vision is to build engineered cells that not only read tissue mechanics but act on them, turning the physical signatures of disease into precise, locally delivered therapeutic programs.
John T. Ngo (Wed,) studied this question.