Microscopy

High-temperature, single-molecule imaging

It is a challenge to image single molecules at temperatures higher than 37 °C because the index-matching fluids used in conjunction with high-numerical-aperture lenses can transfer heat to the lens, causing damage. This has been a limitation for single-molecule sequencing-by-synthesis, preventing the use of thermophilic polymerases. Schwartz et al. now describe tiny TiO2 colloidal lenses that have a high refractive index and are capable of single-molecule imaging at 70 °C, which should improve the efficiency of single-molecule sequencing.

Schwartz, J.J. et al. Nat. Nanotechnol. 5, 127–132 (2010).

Spectroscopy

NMR for membrane-anchored proteins

Membrane-anchored proteins, consisting of a soluble domain and a lipid anchor, are difficult to study by solution NMR spectroscopy without removing the anchor, thus precluding study of its structural role. Valentine et al. now report the use of reverse-micelle technology to obtain high-resolution NMR solution structures for two myristoylated proteins. A surfactant shell, through which the lipid extends, encloses an aqueous solution in which the protein is encapsulated, and the whole assembly is solvated in a low-viscosity liquid ideal for NMR spectroscopy.

Valentine, K.G. et al. Structure 18, 9–16 (2010).

Imaging and visualization

Detecting Fe-S clusters

Proteins containing Fe-S clusters have many essential biological functions, but not much is known about Fe-S cluster metabolism and its role in disease, owing to a lack of tools for imaging Fe-S clusters. Hoff et al. now describe a fluorescent probe to detect Fe-S clusters, based on the complementation of two Venus fluorescent protein fragments when glutaredoxin 2 dimerizes upon coordinating a 2Fe-2S cluster. This approach can be used to image Fe-S cluster proteins in both bacterial and mammalian cells.

Hoff, K.G. et al. Chem. Biol. 16, 1299–1308 (2009).

Chemical biology

Controlled condensation in cells

Controlling chemical synthesis inside cells is a challenge, owing to problems with biocompatibility and selectivity. Liang et al. now report the condensation reaction of 2-cyanobenzothiazole and D-cysteine, which occurs under mild conditions and can take place in living cells under the control of pH, disulfide reduction or enzymatic cleavage. It is promising for use in in vivo molecular imaging applications.

Liang, G. et al. Nat. Chem. 2, 54–60 (2010).

Cell biology

Delivery with vertical silicon nanowires

Shalek et al. demonstrate that DNA, proteins, peptides and small molecules can be delivered into mammalian cells via vertical silicon nanowire arrays. When these nanowires impale the cell membrane, they release their 'cargo' into the cytosol; in all cases shown the introduced molecules carry out their intended functions. No chemical modification or packaging of the delivery agent is needed, and the cells grow and divide normally for several weeks.

Shalek, A.K. et al. Proc. Natl. Acad. Sci. USA 107, 1870–1875 (2010).