Embryonic stem cells (ESC) are both a potential source of cells for tissue replacement therapies and an accessible tool to model early embryonic development. Chemical factors such as soluble growth factors and insoluble components of the extracellular matrix are known to affect the differentiation of murine ESCs. However, there is also evidence to suggest that undifferentiated cells can both sense the mechanical properties of their environment and differentiate accordingly. By growing ESCs on flexible polydimethylsiloxane substrates with varying stiffness, we tested the hypothesis that substrate stiffness can influence ESC differentiation. While cell attachment was unaffected by the stiffness of the growth substrate, cell spreading and cell growth were all increased as a function of substrate stiffness. Similarly, several genes expressed in the primitive streak during gastrulation and implicated in early mesendoderm differentiation, such as Brachyury, Mixl1 and Eomes, were upregulated in cell cultures on stiffer compared to softer substrates. Finally, we demonstrated that osteogenic differentiation of ESCs was enhanced on stiff substrates compared to soft substrates, illustrating that the mechanical environment can play a role in both early and terminal ESC differentiation. Our results suggest a fundamental role for mechanosensing in mammalian development and illustrate that the mechanical environment should be taken into consideration when engineering implantable scaffolds or when producing therapeutically relevant cell populations in vitro.

An atomic force microscope (AFM) has been used to directly monitor specific interactions between antibodies and antigens employed in an immunoassay system. Results were achieved using AFM probes functionalized with ferritin, and monitoring the adhesive forces between the probe and anti-ferritin antibody-coated substrates. Analysis of the force distribution data suggests a quantization of the forces, with a period of 49 +/- 10 pN. This periodic force may be attributed to single unbinding events between individual antigen and antibody molecules. These results demonstrate that the AFM could be employed as an analytical tool to study the interactions between the molecules involved in biosensor systems. The potential of the technique to provide information relating to the manner in which the antibody molecule binds to its specific antigen is also discussed.

The solution properties of a series of transition-metal-ligand coordination polymers [ML(X)(n)](infinity) [M=Ag(I), Zn(II), Hg(II) and Cd(II); L=4,4'-bipyridine (4,4'-bipy), pyrazine (pyz), 3,4'-bipyridine (3,4'-bipy), 4-(10-(pyridin-4-yl)anthracen-9-yl)pyridine (anbp); X=NO(3) (-), CH(3)COO(-), CF(3)SO(3) (-), Cl(-), BF(4) (-); n=1 or 2] in the presence of competing anions, metal cations and ligands have been investigated systematically. Providing that the solubility of the starting complex is sufficiently high, all the components of the coordination polymer, namely the anion, the cation and the ligand, can be exchanged on contact with a solution phase of a competing component. The solubility of coordination polymers is a key factor in the analysis of their reactivity and this solubility depends strongly on the physical properties of the solvent and on its ability to bind metal cations constituting the backbone of the coordination polymer. The degree of reversibility of these solvent-induced anion-exchange transformations is determined by the ratio of the solubility product constants for the starting and resultant complexes, which in turn depend upon the choice of solvent and the temperature. The extent of anion exchange is controlled effectively by the ratio of the concentrations of incoming ions to outgoing ions in the liquid phase and the solvation of various constituent components comprising the coordination polymer. These observations can be rationalised in terms of a dynamic equilibrium of ion exchange reactions coupled with Ostwald ripening of crystalline products. The single-crystal X-ray structures of [Ag(pyz)ClO(4)](infinity) (1), {[Ag(4,4'-bipy)(CF(3)SO(3))]CH(3)CN}(infinity) (2), {[Ag(4,4'-bipy)(CH(3)CN)]ClO(4) 0.5 CH(3)CN}(infinity) (3), metal-free anbp (4), [Ag(anbp)NO(3)(H(2)O)](infinity) (5), {[Cd(4,4'-bipy)(2)(H(2)O)(2)](NO(3))(2)4 H(2)O}(infinity) (6) and {[Zn(4,4'-bipy)SO(4)(H(2)O)(3)] 2 H(2)O}(infinity) (7) are reported.

Catheter-associated urinary tract infection (CAUTI) is the commonest hospital-acquired infection, accounting for over 100,000 hospital admissions within the USA annually. Biomaterials and processes intended to reduce the risk of bacterial colonization of the catheters for long-term users have not been successful, mainly because of the need for long duration of activity in flow conditions. Here we report the results of impregnation of urinary catheters with a combination of rifampicin, sparfloxacin and triclosan. In flow experiments, the antimicrobial catheters were able to prevent colonization by common uropathogens Proteus mirabilis, Staphylococcus aureus and Escherichia coli for 7 to 12weeks in vitro compared with 1-3days for other, commercially available antimicrobial catheters currently used clinically. Resistance development was minimized by careful choice of antimicrobial combinations. Drug release profiles and distribution in the polymer, and surface analysis were also carried out and the process had no deleterious effect on the mechanical performance of the catheter or its balloon. The antimicrobial catheter therefore offers for the first time a means of reducing infection and its complications in long-term urinary catheter users.