Science Concentrates IMAGING
Biosensor maps localized cell activity ‘FLINC’ senses bioactivity at superresolution A new type of fluorescent biosensor makes it possible to visualize enzymatic and cell-signaling activities occurring at highly specific locations in live cells. Such activities often occur at 100-nmsized sites and observing them is currently difficult or impossible. For example, the diffraction limit of visible light prevents light microscopy from capturing dynamic events at sites smaller than 200 to 250 nm. Superresolution techniques such as SOFI (stochastic optical fluctuation imaging) break the diffraction limit of light microscopes. But they can image only static structures in cells, not dynamic bioactivities. Now, Jin Zhang of the University of California, San Diego, and coworkers have developed biosensors that light up cellular processes in a new way and are SOFI-detectable, down to a resolution of about 100 nm (Nat. Methods 2017, DOI: 10.1038/nmeth.4221). They discovered a new biosensing phenomenon called FLINC—Fluorescence fLuctuation INcrease by Contact—in which fluorescence fluctuations speed up when two fluorescent proteins are in close contact. FRET (fluorescence resonance energy transfer) and BiFC (bimolecular fluorescence complementation) have mechanisms reminiscent of FLINC. But FRET is not easily compatible with superresolution imaging, and BiFC is a one-time, irrevers-
ible fluorescence-generation process that can’t track dynamic bioactivity. Zhang and coworkers discovered serendipitously that a fluorescent protein, Dronpa, significantly increases the rate of fluorescence fluctuations of another protein, TagRFP-T, when the two are in close Kinase recognition site
with SOFI to visualize kinase activity in cell microdomains at superresolution. FLINC “is an important step forward that will be useful within the community,” comments John D. Scott of the University of Washington School of Medicine, an expert on cell signaling. “Only time will tell Record fluctuations at cell microdomains
FLINC fluctuations
TagRFP-T
Map activity on membrane or other imaged cell structure
SOFI
Kinase activity
Phosphaterecognition protein domain
Dronpa
Phosphate
proximity. The team created biosensors in which these proteins are placed at either end of a peptide sequence that an enzyme or signaling molecule can recognize and modify. Normally, the biosensors have extended conformations in which the two proteins remain far apart. But when an enzyme modifies the peptide sequence—for example, by phosphorylation—the biosensor changes to a compact shape. This brings the proteins into close proximity and turns on a FLINC signal that can be imaged. Zhang and coworkers used the biosensors
In FLINC, one protein changes the fluorescence of another when enzyme activity brings them close together. as to the generality and utility of this approach, but it’s a promising start.” Zhang’s group “is pitching FLINC as a biosensor technique, but any processes that involve proximity between molecules, such as protein-protein interactions, could be studied using this strategy,” says biomedical optics specialist Xiaolin Nan of Oregon Health & Science University.—STU
BORMAN
HYDROGEN POWER
A sustainable, cleaner-burning alternative to gasoline could help shrink the carbon footprint of cars and trucks. One option is to use methanol by catalytically releasing hydrogen from the liquid to power a hydrogen fuel cell. Ding Ma of Peking University, Beijing, and coworkers report a new catalyst to do so: atomically dispersed platinum over molybdenum carbide particles, which drives the efficient and relatively low-temperature “reforming” of CH3OH and water to form H2 (Nature 2017, DOI: 10.1038/ nature21672). The process is about five times as efficient as the previous H2-from-methanol
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C&EN | CEN.ACS.ORG | MARCH 27, 2017
champ, a ruthenium-catalyzed dehydrogenation developed by Matthias Beller of the University of Rostock and coworkers (Nature 2013, DOI: 10.1038/nature11891). The new Pt/MoC catalyst works at 150 to 190 °C—cooler than the 200 °C or more traditionally used to reform CH3OH vapor and hotter than Beller’s process, which works at 65 to 95 °C. But the new process avoids the Beller reaction’s use of caustic hydroxide, and the heterogeneous Pt/MoC catalyst is cheaper and easier to recycle than Beller’s homogeneous one. Ma calculates that a 50-L tank of CH3OH and catalyst with 6 to 10 g of Pt could power a Toyota Mirai, a hydrogen fuel cell concept
car, for about 690 km. The CH3OH would cost about $15 and the Pt about $320, but the catalyst is potentially recyclable. Reaction engineer Dion Vlachos of the University of Delaware says the new process “has a technological edge in terms of reaction rate,” but improving long-term catalyst stability, developing means for catalyst regeneration, and finding alternatives to noble metals “are important future directions for widespread commercialization.” Beller calls Ma’s catalyst “a major breakthrough,” noting that this type of catalyst might also be useful for other aqueous-phase reforming processes, such as those involving biowaste or ethanol.—STU BORMAN
CREDIT: ADAPTED FROM NAT. METHODS
New process for generating hydrogen fuel
