The spatial elastic modulus distribution of microgel networks in presence and absence of bifunctional crosslinkers is studied by AFM. Thermoresponsive poly(N-isopopylacrylamide) (PNIPAM) and poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate)) (P(MEO2MA-co-OEGMA)) microgel are...

Adhesion processes at the cellular scale are dominated by carbohydrate interactions, including the attachment and invasion of pathogens. Carbohydrate-presenting responsive polymers can bind pathogens and inhibit pathogen invasion by remote stimuli for the development of new antibiotic strategies. In this work, the adhesion forces of E. coli to monolayers composed of mannose-functionalized microgels with thermosensitive poly­(N-isopropylacrylamide) (PNIPAM) and poly­(oligo­(ethylene glycol)) (PEG) networks are quantified using single-cell force spectroscopy (SCFS). When exceeding the microgels’ lower critical solution temperature (LCST), the adhesion increases up to 2.5-fold depending on the polymer backbone and the mannose density. For similar mannose densities, the softer PNIPAM microgels show a significantly stronger adhesion increase when crossing the LCST as compared to the stiffer PEG microgels. This is explained by a stronger shift in swelling, mannose density, and surface roughness of the softer gels when crossing the LCST. When using nonbinding galactose instead of mannose, or when inhibiting bacterial receptors, a certain level of adhesion remains, indicating that also polymer–fimbria entanglements contribute to adhesion. The presented quantitative analysis provides insights into carbohydrate-mediated bacterial adhesion and the relation to material properties and shows the prospects and limitations of interactive polymer materials to control the attachment of bacteria.

The synthesis of carbohydrate-functionalized biocompatible poly(oligo(ethylene glycol) methacrylate microgels and the analysis of the specific binding to concanavalin A (ConA) and Escherichia coli (E. coli) is shown. By using different crosslinkers, the microgels’ size, density and elastic modulus were varied. Given similar mannose (Man) functionalization degrees, the softer microgels show increased ConA uptake, possibly due to increased ConA diffusion in the less dense microgel network. Furthermore, although the microgels did not form clusters with E. coli in solution, surfaces coated with mannose-functionalized microgels are shown to bind the bacteria whereas galactose (Gal) and unfunctionalized microgels show no binding. While ConA binding depends on the overall microgels’ density and Man functionalization degree, E. coli binding to microgels’ surfaces appears to be largely unresponsive to changes of these parameters, indicating a rather promiscuous surface recognition and sufficiently strong anchoring to few surface-exposed Man units. Overall, these results indicate that carbohydrate-functionalized biocompatible oligo(ethylene glycol)-based microgels are able to immobilize carbohydrate binding pathogens specifically and that the binding of free lectins can be controlled by the network density.

The biomolecular interaction of ligand-presenting switchable microgels is studied with respect to the polymer type, composition, and structure of the microgels. Monodisperse microgels are prepared through precipitation polymerization of N-isopropylacrylamide (PNIPAM microgels) or oligo­(ethylene glycol methacrylamide)­s (POEGMA microgels) in the presence of crosslinkers or in their absence (self-crosslinked). Functionalization with mannose or biotin as model ligands and affinity measurements upon heating/cooling are conducted to obtain mechanistic insights into how the microgel phase transition affects the specific interactions. In particular, we are interested in adjusting the crosslinking, swelling degree, and ligand density of mannose-functionalized microgels to reversibly catch and release mannose binding Escherichia coli by setting the temperature below or above the microgels’ volume phase transition temperature (VPTT). The increased mannose density for collapsed microgels above the VPTT results in stronger E. coli binding. Detachment of E. coli by reswelling the microgels below the VPTT is achieved only for self-crosslinked microgels showing a stronger decrease in ligand density compared to microgels with dedicated crosslinkers. Owing to a reduced mannose density in the shell of POEGMA microgels, their E. coli binding was lower compared to PNIPAM microgels, as supported by ultraresolution microscopy. Importantly, an inverse temperature-controlled binding of microgels decorated with hydrophilic mannose and hydrophobic biotin ligands is observed. This indicates that hydrophobic ligands are inaccessible in the collapsed hydrophobic network above the VPTT, whereas hydrophilic mannose units are then enriched at the microgel–water interface and thus are more accessible.