SCIENCE & TECHNOLOGY CONCENTRATES
PUTTING THE SQUEEZE ON CELLS
DOUBLE-DUTY BROMOCATALYST
A new microfluidic device can rapidly analyze the size and rigidity of cells all at once (Anal. Chem., DOI: 10.1021/ac300264v). Cells are a bit like pillows, ranging from hard to soft. Previous high-throughput methods to measure cell stiffness infer the property from the time it takes a cell to travel through a microfluidic channel: Firm cells take longer to squeeze through tiny passageways than soft cells do. But MIT’s Klavs F. Jensen wanted to build a device that also takes into account cell size to improve stiffness measurements. His team’s device consists of a microfluidic path running between two electrodes. By measuring electrical resistance, the researchers can determine the size of a cell passing through. As cell size increases, so does resistance. They can also measure the cell’s transit time via how long this resistance spike lasts. The researchers tested the device on HeLa cells, some of which they softened with a toxin that breaks down the cytoskeleton. As predicted, softer cells took less travel time than harder, untreated cells, and smaller cells traveled faster than larger cells.—JNC
By tweaking a classic catalyst scaffold, chemists have developed a route to lactones that feature bromine at chiral centers (J. Am. Chem. Soc., DOI: 10.1021/ja305117m). It’s an addition to the tool kit of halolactonization, a class of reactions organic chemists use to make natural products with therapeutic potential. Stephen F. Martin of the University of Texas, Austin, and coworkers made two modifications to BINOL, a popular chiral catalyst, to promote bromolactonizations of unsaturated carboxylic acids. They added an amidine substituent to stabilize the reaction’s bromonium ion intermediate and a phenyl group to boost stereoselectivity. The method proceeds through ring closure in which the new C–Br bond is formed outside the ring. It’s the first exo-lactonization to generate chiral centers with high enantioselectivity featuring carbonhalogen bonds, Martin says. The team now plans to study the reaction’s mechanism in greater depth.—CD
SHEAR-ACTIVATED CLOT-BUSTING DRUG
COURTESY OF WYSS I NSTI TUTE
When blood clots form during atherosclerosis or a stroke, the obstruction increases the shear forces of blood in the blocked vessel. Researchers are now taking advantage of these forces to break apart nanoparticle clusters to deliver a clotbusting drug called tissue plasminogen activator (tPA) so that much less of the drug is required (Science, DOI: 10.1126/ This fluorescence science.1217815). micrograph reveals Because tPA causes the cross section of serious side effects, a blocked artery (about 1 mm wide); such as excessive internal bleeding, the the nanoparticlenewdeliverystrategy bound clot-busting drug tPA is shown has the potential to in pink. enhance drug safety, says Harvard University’s Donald E. Ingber, who led the research.Ingber’steamassembledaggregates of poly(lactic-co-glycolic acid) nanopar-
ticles to which they attached tPA via a biotin linker. In normal blood flow, the aggregates remain intact. But near a blockage the increased shear forces break the aggregates apart, releasing the drug for efficient arrival at the clot site. Hurdles remain before the drug delivery system can enter the clinic, including ensuring nanoparticle safety and replacing biotin with a linker that doesn’t activate the human immune system.—SE
RUTHENIUM TWEAKS HELICENE SWITCHING Grafting a ruthenium complex onto the end of a helical fused aromatic ring system known as a helicene provides unprecedented enhancement of the helicene’s chiroptical properties, according to an international research team (J. Am. Chem. Soc., DOI: 10.1021/ja304424t). Helicenes are chiral molecules with a right- or left-hand helical twist. Their derivatives are being studied for their optical properties, which could be used to create redox-triggered molecular switches. Researchers led by Jochen Autschbach of the State University of New York, Buffalo, and Jeanne Crassous and Régis Réau of CNRS-University of Rennes 1, in France, prepared rutheniumvinylhelicenes by adding a ruthenium complex to a terminal alkyne on a hexahelicene. They then studied the electronic properties of the modified helicenes, find-
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ing that oxidizing and reducing ruthenium can drive the chiral switching. Their design provides the first known electrochemical chiral switch made without modifying the helicene core. The organometallic molecular engineering of helicene “opens new perspectives in the design of new advanced chiral multifunctional materials,” the researchers write.—SR
GENE THERAPY FOR SKIN Thanks to scientists at Northwestern University, treating skin cancer might become as easy as rubbing on a nanoparticle-filled lotion (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1118425109). A team led by Chad A. Mirkin and Amy S. Paller demonstrated that, when applied to both mouse skin and engineered human skin, spherical gold nanoparticles coated with densely packed, oriented strands of small interfering RNA penetrated the skin’s many layers. Once past the outer layer, the particles switched off targeted genes inside skin cells. For instance, particles applied to engineered human skin decreased expression of a gene coding for epidermal growth factor receptor by 52%. This protein is overexpressed in a number of cancer cell types. Not only did the researchers observe the particles penetrate skin, they also saw them leave. Ten days after treatment, mice retained only 2% of the gold from the originally absorbed particles.—LKW
