The force-displacement response of a single duplex DNA molecule was measured. The force saturates at a plateau around 70 piconewtons, which ends when the DNA has been stretched about 1.7 times its contour length. This behavior reveals a highly cooperative transition to a state here termed S-DNA. Addition of an intercalator suppresses this transition. Molecular modeling of the process also yields a force plateau and suggests a structure for the extended form. These results may shed light on biological processes involving DNA extension and open the route for mechanical studies on individual molecules in a previously unexplored range.

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We analyze whether the "overstretched," or "S" form of double-stranded DNA consists of essentially separated, or essentially interacting, polynucleotide strands. Comparison of force-extension data for S-DNA and single-stranded DNA shows S-DNA to be distinct from both double helix and single-stranded forms. We use a simple thermodynamical model for tension-melted double-stranded DNA, which indicates that the overstretching transition near 65 piconewtons cannot be explained in terms of conversion of double helix to noninteracting polynucleotide strands. However, the single-strand-like response observed in some experiments can be explained in terms of "unpeeling" of large regions of one strand, starting from nicks on the original double helix. We show that S-DNA becomes unstable to unpeeling at large forces, and that at low ionic strength, or for weakly base-paired sequences, unpeeling can preempt formation of S-DNA. We also analyze the kinetics of unpeeling including the effect of sequence-generated free energy inhomogeneity. We find that strongly base-paired regions generate large barriers that stabilize DNA against unpeeling. For long genomic sequences, these barriers to unpeeling cannot be kinetically crossed until force exceeds approximately 150 piconewtons.