Gelation Landscape Engineering Using a Multi-Reaction Supramolecular Hydrogelator System

Simultaneous control of the kinetics and thermodynamics of two different types of covalent chemistry allows pathway selectivity in the formation of hydrogelating molecules from a complex reaction network. This can lead to a range of hydrogel materials with vastly different properties, starting from a set of simple starting compounds and reaction conditions. Chemical reaction between a trialdehyde and the tuberculosis drug isoniazid can form one, two, or three hydrazone connectivity products, meaning kinetic gelation pathways can be addressed. Simultaneously, thermodynamics control the formation of either a keto or an enol tautomer of the products, again resulting in vastly different materials. Overall, this shows that careful navigation of a reaction landscape using both kinetic and thermodynamic selectivity can be used to control material selection from a complex reaction network

Fuel-Mediated Transient Clustering of Colloidal Building Blocks

Fuel-driven assembly operates under the continuous influx of energy and results in superstructures that exist out of equilibrium. Such dissipative processes provide a route toward structures and transient behavior unreachable by conventional equilibrium self-assembly. Although perfected in biological systems like microtubules, this class of assembly is only sparsely used in synthetic or colloidal analogues. Here, we present a novel colloidal system that shows transient clustering driven by a chemical fuel. Addition of fuel causes an increase in hydrophobicity of the building blocks by actively removing surface charges, thereby driving their aggregation. Depletion of fuel causes reappearance of the charged moieties and leads to disassembly of the formed clusters. This reassures that the system returns to its initial, equilibrium state. By taking advantage of the cyclic nature of our system, we show that clustering can be induced several times by simple injection of new fuel. The fuel-mediated assembly of colloidal building blocks presented here opens new avenues to the complex landscape of nonequilibrium colloidal structures, guided by biological design principles

Regulation of gene expression in Streptococcus pneumoniae by response regulator 09 is strain dependent

Recent murine studies have demonstrated that the role of response regulator 09 (RR09) of Streptococcus pneumoniae in virulence is different in different strains. In the present study, we used a murine pneumonia model of infection to assess the virulence of a TIGR4 rr09 mutant, and we found that TIGR4 Delta rr09 was attenuated after intranasal infection. Furthermore, we investigated the in vitro transcriptional changes in pneumococcal rr09 mutants of two strains, D39 and TIGR4, by microarray analysis. The transcriptional profiles of the rr09 mutants of both strains had clear differences compared to the profiles of the parental wild-type strains. In D39 Delta rr09, but not in TIGR4 Delta rr09, genes involved in competence (e.g., comAB) were upregulated. In TIGR4, genes located on the rlrA pathogenicity islet, which are not present in the D39 genome, appeared to be regulated by RR09. Furthermore, several phosphotransferase systems (PTSs) believed to be involved in sugar uptake (e.g., the PTS encoded by sp0060 to sp0066) were strongly downregulated in D39 Delta rr09, while they were not regulated by RR09 in TIGR4. To examine the role of one of these PTSs in virulence, D39 Delta sp0063 was constructed and tested in a murine infection model. No difference between the virulence of this strain and the virulence of the wild type was found, indicating that downregulation of the sp0063 gene alone is not the cause of the avirulent phenotype of D39 Delta rr09. Finally, expression of rr09 and expression of three of our identified RR09 targets during infection in mice were assessed. This in vivo experiment confirmed that there were differences between expression in wild-type strain TIGR4 and expression in the rr09 mutant, as well as differences between expression in wild-type strain D39 and expression in wild-type strain TIGR4. In conclusion, our results indicate that there is strain-specific regulation of pneumococcal gene expression by RR09