Ion Clustering Regulated by Extreme Nanoconfinement Enables Mechanosensitive Nanochannels

Mechanosensitive ion nanochannels regulate transport by undergoing conformational changes within the nanopores. However, achieving precise control over these conformational states remains a major challenge for both artificial soft and solid pores. Here, we propose an alternative mechanism that modulates the charge carrier density inside nanopores, inspired by transistors in solid-state electronics. This strategy leverages a novel phenomenon of confinement-regulated ion clustering in two-dimensional extremely confined nanochannels, revealed by extensive μs-scale enhanced-sampling molecular simulations based on an <i>ab initio</i>-refined force field and nucleation theory. The resulting <i>force-ion transistor</i> enables the mechanically gated control of ion transport and provides a conceptual foundation for designing ionic mechanical logic gates. Our findings offer new insights into piezochannel mechanosensing and electromechanical coupling in biosystems beyond conformational signaling, opening pathways to integrate artificial ion channels with neuromorphic devices for processing mechanical stimuli.