How to simultaneously manipulate and view a single DNA molecule

Scheme showing the technique used in the study (top) and the resulting image (bottom) Scheme showing the technique used in the study (top) and the resulting image (bottom) Julene Madariaga, CNB-CSIC

¡A new device enables lateral stretching of DNA molecules by applying force in a very controlled manner. Combining this technique with advanced fluorescence microscopy methods allows experiments that require visualization of DNA while it is being manipulated. This integration of state-of-the-art technologies is a powerful tool for molecular biology and biophysics studies.


Seeing an isolated DNA molecule while applying stretching or twisting forces on it can provide valuable information to the scientific community. A study published in the journal Nanoscale describes an effective technique that allows very precise manipulation of a DNA chain, while simultaneously seeing at high resolution what is happening to the molecule, for example, when it interacts with proteins.

The study, carried out by researchers at the Centro Nacional de Biotecnología of the CSIC (CNB-CSIC) in collaboration with the University of Bristol (UK), combines two cutting-edge techniques used in molecular biology and biophysics. One of these, the so-called "magnetic tweezers", allows very controlled stretching of DNA. With the second, a type of fluorescence microscopy termed TIRF, the molecules can be observed at high resolution.

"We have taken the technology one step further. Until now, we applied force on the DNA and detected changes in the molecule’s extension, but we couldn’t see the cause of those changes", explains Fernando Moreno-Herrero, CNB-CSIC scientist and director of the research. "With this study, we make new tools available to the entire scientific community that allow us to apply very precise forces to stretch a DNA molecule and, at the same time, to see which proteins are bound to it or what processes are taking place," indicates Julene Madariaga-Marcos, lead author of the study and a researcher at the CNB-CSIC. According to the researcher, "the equipment and technology available at our laboratory to undertake this type of research are unique in Spain".

Similar methods that combine manipulation and visualization tools have allowed scientists to examine DNA while a virus disassembles or to watch genetic repair proteins in action. In this study, the scientists show the utility of combining magnetic tweezers and TIRF microscopy to see how the ParB protein –which participates in segregation and condensation of the bacterial chromosome– binds to the bacterial DNA.

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