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With the help of semiconductor nanocystals, researchers at the Max Planck Institute for Biophysical Chemistry in Goettingen, Germany, and their collaborators at the Universidad de Buenos Aires are now able to capture movies of signal transmission processes involved in the control of gene expression (Nature Biotechnology, February 2004 issue). This breakthrough is expected to speed up the development of new cancer-curing drugs. Quantum Dots (or QDs) can be used as nano-sized markers to visualize DNA sequences, proteins, or other molecules and track them in the cell. The complexes consisting of QDs and specific ligands, in this case a cellular growth factor, bind to target molecules such as receptors on the cell surface. The QDs glow in a variety of colors and are up to 1000 times brighter than conventional fluorescent dyes.
In a study published in the February issue of the acclaimed science journal Nature Biotechnology, Diane Lidke and her colleagues present results of their experiments with Quantum Dots. These are nano-sized semiconductor crystals a mere ten millionth of a millimeter in diameter that fluoresce in several different colors upon excitation with a laser source. These crystals enabled the researchers to deliver real-time video-clips of signal transmission in the so-called erbB receptor family, important targets for many anti-tumor drugs such as antibodies directed against breast cancer. Among other processes, the movies capture the uptake and subsequent redistribution of the receptor-growth factor complexes into the interior of the cell.
"The in vivo measurements reported in our study revealed new insights into cellular processes and interactions that could previously only be studied on fixed (dead) cells," wrote the researchers, led by Dr. Thomas Jovin, chairman of the Max Planck Institute for Biophysical Chemistry's Department of Molecular Biology. "An understanding of receptor-mediated transduction is essential for rational receptor-targeted cancer therapeutics. Quantitative approaches based on multiple combinations of quantum dots and ligands will be invaluable for such investigations."
In the same issue of Nature Biotechnology, two leading experts in live cell imaging reviewed the results of the study. "Semiconductor nanocrystals can track movements of individual receptors on the surface of living cells with unmatched spatial and temporal resolution", wrote Gal Gur and Yosef Yarden of Israel's Weizmann Institute of Science. "(Other) imaging methodologies have limited spatial and temporal resolution and either require complex manipulation or are able to provide only very brief snapshots of receptor dynamics."
Conventional tools, such as fluorescent dyes and polymer spheres, bleach too quickly - sometimes within seconds - to be of use for extended video images of living cells, according to the researchers. Quantum Dots, on the other hand, are not only very photostable but also very bright, making it possible to trace many elements of the cell for minutes or even hours at a time. Today, the length of observation time is a critical factor for the study of cellular processes, since rapid changes can occur over a time span of seconds or minutes.
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[1] Videos and supplementary information are freely accessible at Nature Biotechnology's web site:
Original work:
Lidke, D.S., P. Nagy, R. Heintzmann, D.J. Arndt-Jovin, J.N. Post, H. Grecco, E.A. Jares-Erijman and T.M. Jovin
Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction
Nature Biotechnology. 22, 198-203, February 2004
Journal
Nature Biotechnology