Shedding Light On Cell Mechanics | November 3, 2014 Issue - Vol. 92 Issue 44 | Chemical & Engineering News
Volume 92 Issue 44 | p. 8 | News of The Week
Issue Date: November 3, 2014 | Web Date: October 31, 2014

DNA-Based Fluorescent Probes Measure Forces That Cells Exert As They Move

Sensors: Two teams independently design similar systems for investigating cell mechanics
Department: Science & Technology
Keywords: DNA, cell mechanics, tension sensor, mechanobiology, fluorescence, hairpin, force
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TENSE MOMENT
When a cell receptor yanks on the Salaita group’s DNA probe, the hairpin opens, the fluorophore and quencher separate, and the fluorophore emits light, signaling the applied force.When a cell receptor yanks on the Chen group’s DNA probe (top scheme)—which is made of a single unit—the hairpin opens, the fluorophore and quencher separate, and the fluorophore emits light. This light emission is a measure of the force applied. The same thing happens when a cell pulls on the Salaita group’s DNA probe (bottom scheme), which is composed of three DNA pieces, including a hairpin.
Credit: Nat. Methods (top), Salaita Lab/Emory U (bottom)
Top scheme shows the Chen group’s DNA probe and the bottom scheme shows the Salaita group’s DNA probe.
 
TENSE MOMENT
When a cell receptor yanks on the Salaita group’s DNA probe, the hairpin opens, the fluorophore and quencher separate, and the fluorophore emits light, signaling the applied force.When a cell receptor yanks on the Chen group’s DNA probe (top scheme)—which is made of a single unit—the hairpin opens, the fluorophore and quencher separate, and the fluorophore emits light. This light emission is a measure of the force applied. The same thing happens when a cell pulls on the Salaita group’s DNA probe (bottom scheme), which is composed of three DNA pieces, including a hairpin.
Credit: Nat. Methods (top), Salaita Lab/Emory U (bottom)

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.”

 
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