Limitations of the Equivalent Neutral Polymer Assumption for Theories Describing Nanochannel-confined DNA

The prevailing theories describing DNA confinement in a nanochannel are predicated on the assumption that wall-DNA electrostatic interactions are sufficiently short-ranged such that the problem can be mapped to an equivalent neutral polymer confined by hard walls with an appropriately reduced effective channel size. To determine when this hypothesis is valid, we leveraged a recently reported experimental data set for the fractional extension of DNA molecules in a 250-nm-wide poly(dimethyl siloxane) (PDMS) nanochannel with buffer ionic strengths between 0.075 and 48 mM. Evaluating these data in the context of the weakly correlated telegraph model of DNA confinement reveals that, at ionic strengths greater than 0.3 mM, the average fractional extension of the DNA molecules agree with theoretical predictions with a mean absolute error of 0.04. In contrast, experiments at ionic strengths below 0.3 mM produce average fractional extensions that are systematically smaller than the theoretical predictions with a larger mean absolute error of 0.15. The deviations between experiment and theory display a correlation coefficient of 0.82 with the decay length for the DNA-wall electrostatics, linking the deviations with a breakdown in approximating the DNA with an equivalent neutral polymer.