Measures the forces (i.e., pull) during ligand-receptor interactions.
- System can be used with any fluorescence microscope.
- System can be conjugated to any protein or peptide of interest.
- Easier to use than similar Atomic Force Microscopy.
- Potential cancer diagnostic use.
The current standards for measuring cellular forces use genetically encoded force sensors, optical tweezers, or magnetic tweezers. Genetic force sensors are challenging to make and can impair the normal function of the protein. Optical and magnetic tweezer experiments are mostly for in vitro studies, and therefore do not allow for real time force measurements in live cells. Researchers at Emory University have developed a novel fluorescence-based system for detecting external cellular forces in live cells - a process technology termed "mechanical tension fluorescent microscopy (MTFM). The technology is based around a platform-bound ligand fused to two domains: a fluorophore and a quencher separated by a linker. In the absence of any binding, the fluorophore/ligand is in close proximity to the quenching signal, and there is no fluorescence. Upon binding to a receptor or other interacting protein, the fluorophore/ligand is pulled away from the platform by these proteins, thereby separating them spatially from the quencher, activating fluorescence. Many of these sensors could be laid out into an array to examine the interactions of entire cells. To measure this flourescence, they developed software that takes the images or video and converts them into a force map, allowing users to detect the forces of this interaction anywhere in the cell.
Beyond laboratory research applications, recent evidence has shown that malignant cancer cells are “softer” than normal cells, as measured by their resistance to an externally applied force. Further uses could include research and diagnostic work to identify the metastatic potential of tumors, as the metastasis of tumor cells is dependent upon their physical interactions with other cells and tissues. Currently, this is measured by atomic force microscopy, a fairly non-intuitive process for many scientists and doctors. This new technology may therefore provide a useful and more user-friendly solution for cancer detection upon further development.
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Proof of principle demonstrated with Epidermal Growth Factor Receptor (EGFR) and integrins.
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