Temperature-Switchable Glycopolymers and Their Conformation-Dependent Binding to Receptor Targets

Abstract

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.

Temperature‐Controlled Adhesion to Carbohydrate Functionalized Microgel Films: An E. coli and Lectin Binding Study

“…[ 52,60 ] For collapsed microgels above the LCST, the accessibility of mannose units might be improved at the surface which would also lead to increased binding. [ 31 ]…”

“…[ 25–30 ] Upon temperature increase, these polymer brushes collapse thereby the density of the carbohydrate residues is increased while decreasing the polymers’ steric repulsion by reducing their excluded volume, which overall increases carbohydrate‐receptor binding. [ 31 ] Although the capture of lectins and bacteria could be readily switched “on” by raising the temperature above the phase transition temperature of the polymer, the release of bacteria or protein by lowering the temperature was not yet reported perhaps due to the strong hysteresis of the switchable glycopolymer brushes in the bound and collapsed state. [ 32 ]…”

Synthesis and self-assembly of amphiphilic precision glycomacromolecules

“…Within the assembly, only a fraction of carbohydrates will actually bind to the bacterial receptors, as observed for phase-separated glycopolymer aggregates. 50 In the future, micellar assemblies from two types of APGs might be used, combining for example binding and non-binding carbohydrate units in a heteromultivalent fashion. It has been successfully demonstrated e.g.…”

Lectin and E. coli Binding to Carbohydrate-Functionalized Oligo(ethylene glycol)-Based Microgels: Effect of Elastic Modulus, Crosslinker and Carbohydrate Density

“…In addition to their straightforward synthesis, microgels allow for preparing robust surface coatings through simple physisorption methods, e.g., via drop-casting, spin coating or dip-coating [31] Carbohydrate-functionalized microgels are highly hydrated and soft, thus mimicking properties of the extracellular matrix or glycocalyx, which sets them apart from other glycan-presenting scaffolds. For synthesizing microgel scaffolds, polymers with a lower critical solution temperature (LCST) are frequently used since they enable well-controlled, narrow-size distributions and temperature-controlled binding to bacteria and free lectins [32][33][34][35][36][37][38][39][40][41]. Typically, these responsive microgels are synthesized using poly(N-isopropylacrylamide) (PNIPAM) with an LCST in the physiological range (32 °C) which is desired for potential biomedical applications [42].…”