Direct detection and measurement of wall shear stress using a filamentous bio-nanoparticle

The wall shear stress (WSS) that a moving fluid exerts on a surface affects many processes including those relating to vascular function. WSS plays an important role in normal physiology (e.g. angiogenesis) and affects the microvasculature's primary function of molecular transport. Points of fluctuating WSS show abnormalities in a number of diseases; however, there is no established technique for measuring WSS directly in physiological systems. All current methods rely on estimates obtained from measured velocity gradients in bulk flow data. In this work, we report a nanosensor that can directly measure WSS in microfluidic chambers with sub-micron spatial resolution by using a specific type of virus, the bacteriophage M13, which has been fluorescently labeled and anchored to a surface. It is demonstrated that the nanosensor can be calibrated and adapted for biological tissue, revealing WSS in micro-domains of cells that cannot be calculated accurately from bulk flow measurements. This method lends itself to a platform applicable to many applications in biology and microfluidics

Phosphorescent Sensor for Robust Quantification of Copper(II) Ion

A phosphorescent sensor based on a multichromophoric iridium(III) complex was synthesized and characterized. The construct exhibits concomitant changes in its phosphorescence intensity ratio and phosphorescence lifetime in response to copper(II) ion. The sensor, which is reversible and selective, is able to quantify copper(II) ions in aqueous media, and it detects intracellular copper ratiometrically.National Institute of General Medical Sciences (U.S.) ((Grant GM065519)Ewha Woman's University (Korea) (RP-Grant 2009

Loss of Pluripotency in Human Embryonic Stem Cells Directly Correlates with an Increase in Nuclear Zinc

The pluripotency of human embryonic stem cells (hESCs) is important to investigations of early development and to cell replacement therapy, but the mechanism behind pluripotency is incompletely understood. Zinc has been shown to play a key role in differentiation of non-pluripotent cell types, but here its role in hESCs is directly examined. By mapping the distribution of metals in hESCs at high resolution by x-ray fluorescence microprobe (XFM) and by analyzing subcellular metal content, we have found evidence that loss of pluripotency is directly correlated with an increase in nuclear zinc. Zinc elevation not only redefines our understanding of the mechanisms that support pluripotency, but also may act as a biomarker and an intervention point for stem cell differentiation

Convenient Synthesis of 6,6-Bicyclic Malonamides: A New Class of Conformationally Preorganized Ligands for f-Block Ion Binding

A general synthetic approach was developed for the preparation of a series of 6,6-bicyclic malonamides, a class of ligands that provide a preorganized binding site for f-block ions (particularly trivalent lanthanides). The approach described is convenient to introduce a variety of functional groups at the amide nitrogens to tune the properties of the ligand without altering the preorganized binding. Each of the ten derivatives (that represent a range of functionality, including R = alkyl, hydroxy, phenyl, ester, perfluorocarbon) reported here derives from a single, readily prepared dialdehyde intermediate. This intermediate is converted to the final products via reductive amination with an appropriately functionalized benzylamine, followed by hydrogenolysis and lactam formation. Because derivatization occurs late in the synthesis, the approach is general, requiring only modification of the purification procedures for each new derivative. To aid in the purification of the bicyclic malonamides, we report a novel complexation-based purification method that takes advantage of the high affinity of the ligand for f-block metals

Bis-Aliphatic Hydrazone-Linked Hydrogels Form Most Rapidly at Physiological pH: Identifying the Origin of Hydrogel Properties with Small Molecule Kinetic Studies

Rheological and small molecule kinetic studies were performed to study the formation and hydrolysis of the bis-aliphatic hydrazone bond. The rate of gelation was found to correspond closely with the rate of bond formation and the rate of gel relaxation with the rate of hydrolysis, indicating that small molecule kinetic studies can play an important role in material design. Furthermore, unlike aryl or acyl hydrazone bonds, the bis-aliphatic hydrazone bond forms rapidly under physiological conditions without requiring aniline catalysis yet maintains a pH-dependent rate of hydrolysis. These results suggest the bis-aliphatic hydrazone bond should find use alongside existing bioorthogonal click chemistries for bioconjugation, biomaterial synthesis, and controlled release applications

Bis-Aliphatic Hydrazone-Linked Hydrogels Form Most Rapidly at Physiological pH: Identifying the Origin of Hydrogel Properties with Small Molecule Kinetic Studies

Rheological and small molecule kinetic studies were performed to study the formation and hydrolysis of the bis-aliphatic hydrazone bond. The rate of gelation was found to correspond closely with the rate of bond formation and the rate of gel relaxation with the rate of hydrolysis, indicating that small molecule kinetic studies can play an important role in material design. Furthermore, unlike aryl or acyl hydrazone bonds, the bis-aliphatic hydrazone bond forms rapidly under physiological conditions without requiring aniline catalysis yet maintains a pH-dependent rate of hydrolysis. These results suggest the bis-aliphatic hydrazone bond should find use alongside existing bioorthogonal click chemistries for bioconjugation, biomaterial synthesis, and controlled release applications