Single linear DNA molecules were bound at multiple sites at one extremity to a treated glass cover slip and at the other to a magnetic bead. The DNA was therefore torsionally constrained. A magnetic field was used to rotate the beads and thus to coil and pull the DNA. The stretching force was determined by analysis of the Brownian fluctuations of the bead. Here, the elastic behavior of individual λ DNA molecules over- and underwound by up to 500 turns was studied. A sharp transition was discovered from a low to a high extension state at a force of ∼0.45 piconewtons for underwound molecules and at a force of ∼3 piconewtons for overwound ones. These transitions, probably reflecting the formation of alternative structures in stretched coiled DNA molecules, might be relevant for DNA transcription and replication.

In a process called "molecular combing," DNA molecules attached at one end to a solid surface were extended and aligned by a receding air-water interface and left to dry on the surface. Molecular combing was observed to extend the length of the bacteriophage λ DNA molecule to 21.5 ± 0.5 micrometers (unextended length, 16.2 micrometers). With the combing process, it was possible to (i) extend a chromosomal Escherichia coli DNA fragment (10 ⁶ base pairs) and (ii) detect a minute quantity of DNA (10 ³ molecules). These results open the way for a faster physical mapping of the genome and for the detection of small quantities of target DNA from a population of molecules.

A detailed experimental and theoretical analysis of the alignment of grafted DNA molecules by a moving meniscus is presented. The existence and extent of the stretching (up to $2.14$ times the unstretched length) depends critically on the properties of the surface. Molecules grafted at both ends exhibit a looplike shape which is scale invariant. An elastic model of this process, which we have called molecular combing, is introduced which (a) yields the extension force on various surfaces, (b) yields a value for the tensile strength of DNA, $476\pm 84\mathrm{pN}$, and (c) describes the shape of the loops with no fitting parameters.