In This Issue
CHEMISTRY
Quantifying protein–nanoparticle binding
Despite the tremendous potential of nanotechnology in biomedicine, little is known about the interaction between nanoparticlesand biological systems. Although some serum proteins that generally bind to nanoparticles have been identified, researchers seek an improved understanding of how these proteins interact with nanoscale particles. Tommy Cedervall et al. employed tailored copolymers in tandem with techniques such as isothermal titration calorimetry and size exclusion chromatography to study protein–nanoparticle binding. The authors examined the rates, affinities, and stoichiometries of this binding in a simple serum model system. The authors found that particle size, hydrophobicity, and protein identity all contribute to nanoparticle–protein association. Smaller particles tended to have less surface coverage, possibly because of the higher curvature interfering with binding. At equilibrium, hydrophobic particles had more coverage, although albumin, the most prevalent serum protein, displayed lower exchange rates for hydrophilic particles. The high variation in protein interactions depending on particle composition revealed that many technical hurdles remain in fully characterizing protein–nanoparticle interactions. Still, these techniques may be well suited to determine which proteins from a complex mixture are presented on nanoparticle surfaces, helping to predict the biological effects of nanoparticles. — N.Z.
Gel filtration of nanoparticle–protein mixture.
“Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinites of proteins for nanoparticles” by Tommy Cedervall, Iseult Lynch, Stina Lindman, Tord Berggård, Eva Thulin, Hanna Nilsson, Kenneth A. Dawson, and Sara Linse (see pages 2050–2055)
DEVELOPMENTAL BIOLOGY
Tumor suppressor gene role in bone formation
A network of morphogens and growth factors regulates the life span and activity of osteoblasts, cells that control bone formation and maintenance. Some factors, such as phosphatidylinositol 3-kinase (PI3K), enhance osteoblast survival by activating a specific kinase and thwarting apoptosis. Previous reports have shown that Pten phosphatase, a known tumor suppressor gene, inhibits PI3K. Ximeng Liu et al. investigated the role of Pten phosphatase on bone formation in vivo by conditionally disrupting the Pten gene in osteoblasts. The authors showed that mice lacking Pten expression in osteoblasts grew to a normal size but exhibited increasing bone density throughout life. Liu et al. attribute this rise in bone mass throughout the skeleton to an increase in the number of osteoblasts and a lower rate of apoptosis. The findings demonstrate an important role for Pten in bone formation. This link also supports the observation that some patients with germ-line mutations in Pten display skeletal deformities. — B.T.
Pten disruption increases femur bone volume.
“Lifelong accumulation of bone in mice lacking Pten in osteoblasts” by Ximeng Liu, Katia J. Bruxvoort, Cassandra R. Zylstra, Jiarong Liu, Rachel Cichowski, Marie-Claude Faugere, Mary L. Bouxsein, Chao Wan, Bart O. Williams, and Thomas L. Clemens (see pages 2259–2264)
GENETICS
Selective cell killing via reconstituted caspases
Caspases are enzymes that carry out apoptosis and are normally synthesized as inactive precursors that are then activated by proteolytic processing of their subunits. Using caspases from Caenorhabditis elegans and humans, Dattananda Chelur and Martin Chalfie developed a technique that brings together the subunits of the caspase enzymes to selectively kill cells. The authors separated the coding sequences of the two subunits of caspase, added additional sequences to help link them, and gave each a separate promoter. Expression of the subunits resulted in a constitutively active caspase enzyme, which led to apoptosis. Without the association domains, no cell death occurred. The resulting caspase was termed rec-Caspase,for “reconstituted caspase.” Because the gene for each subunit could be expressed from different promoters, including inducible promoters, recCaspase could be made in specific cells and at specific times. Specific cell death in C. elegans and human cell types in culture was demonstrated by using recCaspase. The technique could be expanded to other cell types and species to induce cell death before or after the development of a tissue or cell line, the authors say. — P.D.
Cell killing by recCaspases in C. elegans
“Targeted cell killing by reconstituted caspases” by Dattananda S. Chelur and Martin Chalfie (see pages 2283–2288)
MICROBIOLOGY
Bacterial protein uses light to power flagella
Proteorhodopsin, a bacterial light-driven proton pump, was identified in 2000 in ocean water samples. The protein absorbs green light and pumps protons out of the cell, but researchers have yet to determine whether it acts as an alternative or complementary energy source. Jessica Walter et al. postulated that proteorhodopsin-containing bacteria use light energy to create a proton motive force (PMF) that can power the bacterial flagella under conditions where normal cellular respiration is impaired, as might occur in a toxic.environment. The authors treated proteorhodopsin-containing Escherichia coli with azide, a respiratory poison that reduces the PMF, thereby slowing the flagellar motor. Under these conditions, green light increased the velocity of proteorhodopsin-containing bacteria. The cells slowed to their previous speed when the light was removed. The results demonstrate that proteorhodopsin provides bacteria with the ability to withstand respiratory poisons and oxygen depletion by augmenting the cellular PMF. Walter et al. suggest that creating a variety of light-powered bacteria to study PMF-dependent processes, such as ion transport, as well as to optically control the behavior of synthetically engineered organisms, may be possible. — M.M.
Green, but not red, light leads to flagella rotation in proteorhodopsin-expressing E. coli.
“Light-powering Escherichia coli with proteorhodopsin” by Jessica M. Walter, Derek Greenfield, Carlos Bustamante, and Jan Liphardt (see pages 2408–2412)
NEUROSCIENCE
Menstrual cycle modulates reward pathways
Fluctuating hormones during the female menstrual cycle affect more than just reproduction. Estradiol and progesterone can impactcognitive ability, moods, pain sensitivity, and even susceptibility to substance abuse. Imaging studies by Jean-Claude Dreher et al. show that the brain's reward pathways change in response to the specific phase of a woman's menstrual cycle. The dopaminergic neurons that control the reward system have receptors for both estradiol and progesterone, but little was known about how the hormones and their changing levels affect neural activity in humans. Dreher et al. studied the brain activity of 15 women, at specific points in the menstrual cycle, as the women engaged in a hypothetical monetary reward game. The authors found that, in the phase 4–8 days after the onset of a menstrual period, when estrogen is present without progesterone, the reward system was much more reactive. The existence of such shifts in perceived rewards of a given action could offer insight into treating drug abuse, mood disorders, and other neurological problems. — T.D.
Cross-menstrual cycle phase differences during reward anticipation.
“Menstrual cycle phase modulates reward-related neural function in women” by Jean-Claude Dreher, Peter J. Schmidt, Philip Kohn, Daniella Furman, David Rubinow, and Karen Faith Berman (see pages 2465–2470)
