High Frequency Cell Mechanostimulation

Cells are known to respond to diverse forms of mechanical cues, yet most mechanostimulation studies have been conducted at low frequencies—typically several Hz, characteristic of the physiological frequencies experienced by cells in their local environment. Higher frequency vibrational mechanotransduction has largely been limited to the kHz range, and it has been suggested that there is no significant advantage in utilising higher frequencies. In contrast, we have observed 10 MHz order nanoscale vibrational stimulation to be capable of eliciting unique and novel cellular responses in a similar manner to our prior discoveries of nonlinear high frequency vibrational coupling into fluids and crystalline materials. These include modulation of mechanosensitive ion channels and transient yet reversible permeabilisation of the cell membrane, which have implications for efficient intracellular cytosol delivery, exosome biogenesis, cytoskeletal reorganisation, endothelial barrier modulation and stem cell differentiation—all while maintaining very high cell viability (>95%). These findings highlight the potential of high-frequency mechanostimuli as a powerful and underexplored paradigm for mechanobiology and cell engineering.