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 lambda 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 approximately 0.45 piconewtons for underwound molecules and at a force of approximately 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 combining," 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 lambda 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.

We study DNA supercoiling in a quantitative fashion by micromanipulating single linear DNA molecules with a magnetic field gradient. By anchoring one end of the DNA to multiple sites on a magnetic bead and the other end to multiple sites on a glass surface, we were able to exert torsional control on the DNA. A rotating magnetic field was used to induce rotation of the magnetic bead, and reversibly over- and underwind the molecule. The magnetic field was also used to increase or decrease the stretching force exerted by the magnetic bead on the DNA. The molecule's degree of supercoiling could therefore be quantitatively controlled and monitored, and tethered-particle motion analysis allowed us to measure the stretching force acting on the DNA. Experimental results indicate that this is a very powerful technique for measuring forces at the picoscale. We studied the effect of stretching forces ranging from 0.01 pN to 100 pN on supercoiled DNA (-0.1 < sigma < 0.2) in a variety of ionic conditions. Other effects, such as stretching-relaxing hysteresis and the braiding of two DNA molecules, are discussed.

This review is an expository treatment of the displacement of one Ouid by another in a two-dimensional geometry (a Hele-Shaw cell). The Saffman-Taylor equations modeling this system are discussed. They are simulated by random-walk techniques and studied by methods from complex analysis. The stability of the generated patterns (fingers) is studied by a WKB approximation and by complex analytic techniques. The primary conclusions reached are that (a) the fingers are linearly stable even at the highest velocities, (b) they are nonlinearly unstable against noise or an external perturbation, the critical amplitude for the noise being an exponential function of a power of the velocity for high velocities, (c) such exponentials seem to dominate high-velocity behavior, as can be seen from a WKB analysis, and (d) the results of the Saffman-Taylor equations disagree with experiments, apparently because they leave out film-flow phenomena.