Mechanical deformation of dsDNA molecules inside square nanochannels is investigated using simulations based on a coarse-grained model of DNA. The combined action of confinement and weak external forces is explored in a variety of confinement regimes, including the transition zone relevant to nanofluidic experiments. The computed free energy and force profiles are markedly affected by the channel size. Effective elastic softening of confined DNA molecules relative to the bulk DNA is observed in the channels of intermediate widths. The extension of DNA from its bulk equilibrium length in nanofluidic devices is resolved into contributions from the passive extension due to confinement and from the active stretching induced by force. Potential implications of the very different energy costs computed for the two extension modes (extension by confinement takes much more free energy than stretching by force) for behavior of DNA in nanofluidic chips are indicated.
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