When cancer cells migrate through the body, they navigate by chemically and mechanically sensing their environment. Recently, researchers have begun to focus on mechanical sensing, hoping to intervene in cancer metastasis by better understanding how cells push and pull on their surroundings.
Two independent research teams have now designed DNA-based fluorescent molecules to probe the forces that cancer and other cells exert when they stick to or move across surfaces.
One team, led by Christopher S. Chen of Boston University, synthesized its probe starting with a DNA hairpin. This short oligonucleotide loops back on itself like a bobby pin, its ends binding with one another. To one end of the hairpin, the team synthetically added a fluorescent group and a peptide called RGD. To the other end, they added a quencher and a group to anchor the entire assembly to a microscope slide.
When cells “crawled” across a slide coated with these probes, receptors on the cells’ surfaces yanked on the peptides, opening the hairpins and enabling their fluorescent groups to emit light (Nat. Methods 2014, DOI: 10.1038/nmeth.3145). By calibrating the probes, Chen and his team were able to determine how hard cells pulled on the surfaces.
Another team, led by Khalid Salaita of Emory University, used a DNA hairpin as a force probe, too, but took a different approach. The researchers’ probe has three units. One is a DNA hairpin with extended arms. The other two are short DNA sequences that bind to each arm: One contains a fluorophore and peptide, and the other contains a quencher and anchor group (Nat. Commun. 2014, DOI: 10.1038/ncomms6167).
“The advantage of our system is that it’s modular,” Salaita says, noting that researchers can slot different hairpins into the probe for testing. The Chen group’s probe involved a more elaborate synthesis, Salaita adds, but it’s also more stable over time.
According to Brenton D. Hoffman of Duke University, with these new probes, “we will be able to start studying mechanical processes with the resolution and sensitivity that have been available for biological processes for several years now.”