The experimentally observable dynamical landscape of biomolecules is fundamentally shaped by rapid thermal motions of the surrounding aqueous environment. Although lowering temperature could expand this observable landscape, the liquid-solid phase transition of water has long prevented real-time single-molecule measurements into deeply subzero aqueous environments. Here we show that nanoconfinement within a solid-state nanopore overcomes the fundamental limitation imposed by bulk water freezing, spontaneously stabilizing a persistent liquid-in-ice environment that remains electrically accessible despite surrounding electrolyte crystallization. This aqueous environment creates a time-stretched dynamical regime, extending molecular translocation timescales by up to ~400-fold and revealing previously inaccessible single-molecule dynamics. These findings establish a new low-temperature aqueous regime for real-time single-molecule measurements, opening new opportunities to investigate biomolecular dynamics across previously inaccessible timescales and extreme aqueous environments.
Liu, S.-C., Wang, J., Xie, Y.-L., Chen, H., Li, Y.-X., Ying, Y.-L., Long, Y.-T.
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