Optical Tweezers: Research

Physicists use optical tweezers to investigate how the genetic information in chromosomal DNA is “read” during cell reproduction. The base sequences that carry the genetic code lie between the two sugar-phosphate backbones of the DNA molecule, and these bases must be exposed to replicate the DNA. In the chromosome, though, the DNA is wound around and around proteins, which in higher organisms are called histones. This wrapping is functional, since it enables the long DNA molecules to fit into the cell, but the DNA must be unwrapped before it is copied. In life, the enzyme DNA polymerase makes the copy, and associated proteins unwrap the DNA biochemically from the histone.

Optical tweezers hold up one end of the DNA/histone complex, while the other end is fastened to a microscope slide. The slide is slowly moved to unwrap the DNA from the histone. (drawing courtesy of Michele Wang/Cornell University)

A group of biophysicists at Cornell and the University of Massachusetts investigated the beginning of this process by unwinding DNA from the histone mechanically. They attached one end of a DNA strand to a microscope slide and the other to a tiny transparent sphere. Then they pulled on the sphere with optical tweezers, like a mini tractor beam, to unwind the DNA, as shown in the diagram.

The group found that the DNA unwound in distinct stages, with increasing force required at each stage (see second diagram). Remarkably, even with 156 bases unwound from the histone, releasing the force enabled the DNA to spontaneously rewrap and return to its original state. These results showed that the enzymes that unwrap the DNA must be “molecular motors,” capable of exerting forces, and some of these have indeed been found.

This work is just one of the many applications of optical tweezers.