Science Concentrates

Forsterite synthesis revisited
Cross-linking protein matrix directs neuron growth
Spiny growth mechanism revealed
Berberine cuts cholesterol
Assay route to better enzymes

Forsterite synthesis revisited

Forsterite (Mg₂SiO₄) is a form of the mineral olivine used as an insulator in high-frequency electronics and other applications. When doped with chromium, it is used in laser optics. Forsterite typically is made from MgO and SiO₂ by solid-state synthesis above 1,100 °C. Now, a research team led by Raymond Whitby of the University of Sussex, in England, has devised a lower temperature method to make forsterite that produces leaflike microstructures with a geometric ordering that hasn't been seen before [Chem. Commun., 2004, 2396]. The team loaded a reaction tube with two separate reactants--a Mg/I₂ mixture and amorphous SiO₂--spaced 20 cm apart. Under a helium atmosphere, the Mg/I₂ powder was heated to 800 °C and the SiO₂ was heated to 600 °C, creating a temperature gradient. Cabbagelike Mg₂SiO₄ crystals formed (shown), as well as catenated crystals that resemble segmented earthworms. The researchers believe MgI₂ is formed as an intermediate species that ferries Mg to SiO₂ nucleation sites, where the forsterite crystals grow. They have shown that the synthesis is reproducible and plan to continue to investigate the nanoscale growth mechanism and to prepare chromium-doped forsterite.

Cross-linking protein matrix directs neuron growth

Neuroscientists often use simplified model systems to study how neurons work. A common approach is to develop cell cultures on a planar substrate and allow a small number of neurons to interact and develop into circuits. The ability to direct the development of neurons in such cultures with micrometer-scale resolution would be a powerful tool. Working toward that goal, Jason B. Shear, associate professor of chemistry and biochemistry at the University of Texas, Austin, and coworkers are using a multiphoton method to excite photosensitizers that promote the cross-linking of various proteins into a matrix from a solution in which neurons are growing [Proc. Natl. Acad. Sci. USA, 101, 16104 (2004)]. "We can create physical structures that cells interact with and respond to," Shear says. Even the simplest cross-linked protein matrices consisting of low-profile lines could be used to redirect the growth of neurons. "We're actively working on adapting this for a more sophisticated system that is a combination of both physical and chemical cues," Shear says.

Spiny growth mechanism revealed

One of the great biomineralization marvels is the ability of sea urchins to grow spines that are complex and porous, yet made up of single, magnesium-rich calcite crystals. Understanding this mechanism would be a boon for materials scientists as well as biologists. It's known that sea urchin larvae build up their spines by first producing an amorphous calcium carbonate, which, after taking on the complex shape, crystallizes into calcite. Now, Lia Addadi, chair in biological ultrastructure at Weizmann Institute of Science, Rehovot, Israel, and colleagues show that the same process occurs when adult sea urchins rebuild spines that have broken [Science, 306, 1161 (2004)]. Using infrared spectroscopy and other techniques, the group monitored the growth of adult sea urchin spines and also showed that amorphous CaCO₃ likely dehydrates during crystallization. The authors say this mechanism for calcite formation is probably widespread and used by all echinoderms.

Berberine cuts cholesterol

Berberine (shown) is a plant alkaloid with manifold biological effects. Now, it has been shown to be a cholesterol-lowering agent in humans that acts via a mechanism different from that of statins. According to Jian-Dong Jiang of the Chinese Academy of Medical Sciences' Institute of Medicinal Biotechnology, Beijing, and colleagues, berberine increases the activity of extracellular-regulated protein kinase (ERK), with the end result that more receptors of low-density lipoproteins (LDLs) are formed on the surface of liver cells. With more receptors, removal of LDLs and the cholesterol they contain--the bad cholesterol--is enhanced [Nat. Med., published Nov. 7, http://dx.doi.org/10.1038/nm1135]. Statins also increase the number of LDL receptors, but they do so through their effect on sterol regulatory element-binding proteins. Commenting on the work, Pfizer researcher H. James Harwood Jr. says ERK could be a new target for lowering cholesterol. "We have applied for patent protection of this discovery in China," Jiang says.

Assay route to better enzymes

Chemical complementation, a general assay for enzyme catalysis, has been applied for the first time to the directed evolution of an enzyme. The technique, developed two years ago by Virginia W. Cornish and coworkers at Columbia University, uses the yeast three-hybrid assay to link enzymatic bond-making or -breaking to detectable changes in reporter-gene transcription [Proc. Natl. Acad. Sci. USA, 99, 16537 (2002)]. Cornish's group has now demonstrated the assay's applicability to directed evolution by using it to screen a small library of mutated glycosynthases (enzymes useful for carbohydrate synthesis), yielding a variant with fivefold-increased activity [J. Am. Chem. Soc., 126, 15051 (2004)]. Stephen G. Withers of the University of British Columbia, Vancouver, whose group recently evolved glycosynthases by rational design and random mutagenesis, comments that "it is very gratifying to see that [chemical complementation] identifies the same improved mutants we found. It's a creative approach to a difficult problem and worthy of much deeper investigation. It will be interesting to see it applied to a larger library, where the true power of selection can come to the fore."