Nanoconfinement greatly speeds up the nucleation and the annealing in single-DNA collapse.

Manipulating and measuring single-molecule dynamics and reactions in nanofluidics is a rapidly growing field with broad applications in developing new biotechnologies, understanding nanoconfinement effects in vivo, and exploring new phenomena in confinement. In this work, we investigate the kinetics of DNA collapse in nanoslits using single T4-DNA (165.6 kbp) and λ-DNA (48.5 kbp), with particular focus on the measurement of the nucleation and annealing times. Fixing the ethanol concentration at 35% and varying the slit height from 2000 to 31 nm, the nucleation time dramatically decreases from more than 1 hour to a few minutes or less. The increased collapsed rate results from the larger free energy experienced by coiled DNA in confinement relative to compacted DNA. Our results also shed light on other conformational transitions in confinement, such as protein folding.