Space-resolved manipulation of biological macromolecules

In conventional biochemistry, there has been no method to allow space-resolved access to a particular position in a molecule. This is due partly to a lack of the molecular manipulation method. A chain like macromolecule, such as DNA, takes randomly coiled conformation and fluctuates due to Brownian motion. Hence, to allow external access, it has to be immobilized with a proper conformation first. The authors use high-intensity high-frequency electric field (less than or equal to 106 V/m, approximately equals 1 MHz) created in micro-machined electrodes to (1) stretch a flexible molecule, (2) align parallel to the field, and/or (3) position onto a substrate either electrically or with the use of molecular bindings. It has been shown that DNA is stretched to full length (0.34 nm per base) under the electrostatic field. Once stretch-and- positioned, position-dependent modifications become possible. It is demonstrated that (1) a stretched DNA can be cut at arbitrary position by ultra-violet laser beam, (2) local temperature rise created by a laser manipulated-and-heated microbead induces pin-point conformational change of a bacterial flagellum ('tail'). The spatial resolution enabled by the electrostatic stretch-and-positioning will find applications not only in biochemical assays, in particular DNA sequencing, but also in the basic research of biomolecular interactions.