Living organisms can sense extracellular forces via mechanosensitive ion channels, which change their channel conformations in response to external pressure and regulate ion transport through the cell membrane. Such pressure-regulated ion transport is critical for various biological processes, such as cellular turgor control and hearing in mammals, but has yet to be achieved in artificial systems using similar mechanisms. In this work, we construct a nanoconfinement by reversibly blocking a single nanopore with a nanoparticle and report anomalous and ultra-mechanosensitive ionic transport across the resulting nanoconfinement upon assorted mechanical and electrical stimuli. Our observation reveals a suppressed ion conduction through the system as the applied pressure increases, which imitates certain behaviors of stretch-inactivated ion channels in biological systems. Moreover, pressure-induced ionic current rectification is also observed despite the high ionic concentration of the solution. Using a combined experimental and simulation study, we correlate both phenomena to pressure-induced nanoparticle rotation and the resulting physical structure change in the blocked nanopore. This work presents a mechanosensitive nano-confinement requiring minimal fabrication techniques and provides new opportunities for bio-inspired nanofluidic applications.

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