The synthesis of carbohydrate-functionalized thermosensitive poly(Nisopropylacrylamide) microgels and their ability to bind carbohydrate-binding pathogens upon temperature switch are reported. It is found that the microgels' binding affinity is increased above their lower critical solution temperature (LCST), enabling thermotriggerable capture of pathogens. Here, a series of microgels with comparatively low mannose functionalization degrees below 1 mol % is achieved by a single polymerization step. Upon increase in mannose density, the microgel size increases, and the LCST decreases to 26 °C. Clustering with concanavalin A indicated that binding affinity is enhanced by a higher mannose content and by raising the temperature above the LCST. Binding studies with Escherichia coli confirm stronger specific interactions above the LCST and formation of mechanically stable aggregates enabling efficient separation of E. coli by filtration. For small incubation times above the LCST, the microgels' potential to release pathogens again below the LCST is confirmed also. Compared to existing switchable scaffolds, microgels nearly entirely composed of a thermosensitive material undergo a large change in volume, which allows them to drastically vary the density of ligands to switch between capture and release. This straightforward yet novel approach is likely compatible with a broad range of bioactive ligands. Therefore, thermosensitive microgels represent a promising platform for the specific capture or release of cells or pathogens.

The temperature-dependent binding of copolymers from poly(N-isopropylacrylamide) (PNIPAM) and mannose ligands to Escherichia coli and concanavalin A (ConA) is determined. Through polymer analogous reactions using poly(N-acryloxysuccinimide) and amine-linked mannose residues with different linkers, glycopolymers are prepared with the variation of the mannose density. Quantitative adhesion inhibition assays show the inhibitory potential of the glycopolymers as a function of the mannose/NIPAM ratio and linker type above and below their lower critical solution temperature (LCST). Intriguingly, opposite temperature effects on the binding to E. coli and ConA are observed. While the E. coli inhibition is stronger above the LCST, the ConA inhibition is, in overall, weaker at elevated temperatures. When going beyond the LCST, the polymers undergo a coil-to-globule transition, forming microphases with surface-enriched hydrophilic sugar moieties exhibiting increased E. coli inhibition through steric shielding. However, the formation of such microphases above the LCST renders a fraction of carbohydrate ligands inaccessible,and the polymers remaining in the solution phase then have coil sizes below the minimum binding site spacing of the ConA receptor, explaining reduced ConA inhibition. Overall, these results suggest that the coil-to-globule transition of glycopolymers may induce lower or higher inhibitory potentials due to the adverse effects of steric shielding and carbohydrate ligand accessibility.

Adhesive processes mediated by carbohydrate‐decorated interfaces play a crucial role in many biological processes such as cell development or pathogen invasion. The involved carbohydrate scaffolds are soft and present multiple subsites forming complex and dynamic bonds to carbohydrate binding proteins. New tools and data are needed to understand how ligand presentation and mechanical properties drive these binding processes. This article highlights recent developments in the area of adhesion assays with a focus on soft biomimetic carbohydrate scaffolds as probes of adhesion forces. Key findings state that carbohydrate functionalized polymer networks largely show additive multivalency (statistical effects) and that the overall interaction forces are strongly affected by the stiffness of the network. These results indicate that phase transitions of carbohydrate bearing polymer gels may enable tunable affinity toward carbohydrate binding proteins. As an example, polymer networks undergoing large changes in mechanical rigidity, density, and spacing of carbohydrate ligands upon temperature stimulus are shown to bind or release carbohydrate binding bacteria such as Escherichia coli. The presented adhesion assays and the developed responsive systems can provide new insights into the mechanism through which carbohydrates mediate adhesion processes and establish new avenues toward scaffolds for the capture or release of cells or pathogens.

Catechol and amine residues, both abundantly present in mussel adhesion proteins, are known to act cooperatively by displacing hydration barriers before binding to mineral surfaces. In spite of synthetic efforts...