3-D PRINTING BIOCHEMISTRY
CREDIT: NAT. MAT E R.
New roles for heat-shock proteins When a biological cell is under duress, a family of heat-shock proteins called Hsp70 steps in to help unfolded peptide chains refold into functional proteins. The same family also helps prefolded peptide chains find a correct three-dimensional conformation in cells. But Hsp70s have a lot more tricks up their sleeves, according to a team led by Sander J. Tans of Fundamental Research on Matter’s Institute for Atomic & Molecular Physics (Nature 2016, DOI: 10.1038/ nature20137). The researchers have found that Hsp70s also bind mature, folded proteins and interact with intermediates in folding processes, which “suggests that Hsp70s play a bigger part in protein homeostasis than was thought,” comment Qinglian Liu of Virginia Commonwealth University and Elizabeth A. Craig of the University of Wisconsin, Madison, in an associated Nature commentary (DOI: 10.1038/ nature20470). For example, Hsp70s bind protein receptors and kinases, whose structure and conformation can change as part of their job in the cell. This suggests Hsp70s may play a role in regulation of basic cellular processes—instead of just being cellular paramedics. Tans tells C&EN that it’s been difficult to determine the full functional potential of the Hsp70 family because some of the protein structures it interacts with are transient in the cell and thus hard to observe. So Tans’s team used optical tweezers to modify the conformations of single proteins and then see how Hsp70s responded. In doing so, the researchers found that Hsp70s’ repertoire is much broader than previously thought.—SARAH EVERTS
The telltale hearton-a-chip device Three-dimensional printed devices coupling living tissue and sensors could one day screen drugs Harvard University researchers may be one step closer to replacing lab rats with labgrown organ tissue thanks to inky chemistry and three-dimensional printing. Led by Kevin Kit Parker and Jennifer A. Lewis, the team 3-D printed devices that encourage the growth of heart cells and then electronically monitor the beating of the resulting tissue (Nat. Mater. 2016, DOI: 10.1038/nmat4782). This is the first time researchers have coupled living tissue with sensor electronics entirely through 3-D printing, Lewis says. Sometimes referred to as an organ-on-a-chip, this type of device could become the basis for future bionic implants and prosthetics but may sooner help evaluate new drug candidates in place of animal models, she adds. To print its new platforms, the team formulated several functional “inks” for its custom 3-D printer. For instance, the researchers concocted an ink that mixes thermoplastic polyurethane with carbon black nanoparticles to print flexible but conductive sensor loops. Printing these loops between insulating layers of a pure polyurethane ink created layered cantilever structures that can flex like extremely elastic diving boards. The team capped the cantilevers by printing layers of polydimethylsiloxane with grooves that guided cardiac cells—sourced from rats and generated from human stem cells—to self-assemble into thin layers of pulsating tissue. The tissue’s movement drives the underlying cantilever to bend, altering the conductivity of the sensor loop within. The loops are connected to external equipment, such as oscilloscopes and power supplies, with the help of a silver-laden ink. This enables devices to convert the tissue’s mechanical beat into an electrical signal. As a proof of concept, the team showed that its cardiac-tissue-on-a-chip responded to a pair of approved pharmaceuticals—verapamil and isoproterenol—and electronically reported their effects. Verapamil, a medication for high blood pressure, slowed the beating of a device’s cardiac tissue and diminished the strength of its contractions. Isoproterenol, a drug used to treat slow heart rate, increased both the tissue’s strength and beat frequency.
Cardiac tissue
Sensor deflection Tissue contraction
This 3-D printed heart chip contains multiple chambers, each with cardiac tissue and an electronic strain sensor. Although it remains to be seen whether such devices can reliably screen novel drug candidates, this work highlights the promise of 3-D printing in creating organs-on-a-chip, says Michael C. McAlpine of the University of Minnesota, Twin Cities. McAlpine’s group 3-D printed a platform for observing how viruses affect neurons last year (Lab Chip 2015, DOI: 10.1039/c5lc01270h). Researchers developed earlier organs-ona-chip relying largely on photolithography and other clean-room fabrication techniques that are often incompatible with living cells, McAlpine says. The Harvard team demonstrated that 3-D printing can build up fully functional devices in a biocompatible way. “We’ve shown we can go all the way from printing living cells to synthetic materials,” Lewis says, adding that the approach can be adapted to produce other types of tissue and sensors.—MATT DAVENPORT OCTOBER 31, 2016 | CEN.ACS.ORG | C&EN
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