Quantifying Thermoswitchable Carbohydrate‐Mediated Interactions via Soft Colloidal Probe Adhesion Studies

Abstract

affinity of linked biomolecules, e.g., by varying their accessibility to control their specific binding. Thermoresponsive polymers with a lower critical solution temperature (LCST) between 30 and 40 °C are most frequently used for such applications, where poly(N-isopropyl acrylamide) (PNIPAM), poly(N-vinyl caprolactam) or poly(oligoethylene glycols) are well-known examples. [10] As bioligands conjugated to such LCST polymers, carbohydrates have recently gained attention since they dominate biomolecular interactions on the cellular level and drive numerous physiological processes in the healthy or diseased state. [11] For example, lectins, a class of carbohydrate binding proteins, mediate cell adhesion, communication, fertilization, or pathogen invasion. [12,13] To target carbohydrate binding pathogens or lectins directly, responsive carbohydrate ligand presenting polymers are being employed in microgels, [14-16] on nano particle surfaces, [17-19] 2D-surface coatings, [4] and linear or branched polymers. [20-23] Although many studies could show a temperature controllable affinity shift of thermoresponsive glycopolymers, the cause for this behavior and the molecular details are not well understood. For example, when increasing the temperature above the LCST, some studies found that the affinity increased, [16,17,24] whereas other studies obtained decreasing carbohydrate binding affinities. [4,20,21] The factors that may increase the binding affinities upon temperature increase are: 1) an increase of carbohydrate subunit density due to an increase of statistical rebinding or subsite binding. [25-27] 2) An increase of carbohydrate surface density due to the formation of a compact polymer globule where the hydrophilic carbohydrates enrich at the surface. [28] 3) A smoother surface upon polymer collapse leading to a reduced steric repulsion. [29,30] On the other hand, the collapse of the thermoresponsive polymer above the LCST can lead to a reduced accessibility of the carbohydrate units, e.g., due to the more compact polymer globules or aggregate formation. [21] These potentially negating mechanisms make it hard to predict the change in glycopolymer affinity upon the temperature induced coil-to-globule transition. In addition, the use of these materials is often motivated by being able to remotely "switch" the ligand-receptor interaction on and off, implying reversible ligand-receptor complex formation and dissociation. However, such reversible binding of LCST polymers was rarely shown and typically limited to Thermosensitive polymers enable externally controllable biomolecular interactions but hysteresis effects hamper the reversibility and repeated use of these materials. To quantify the temperature-dependent interactions and hysteresis effects, an optical adhesion assay based on poly(ethylene glycol) microgels (soft colloidal probes, SCPs) with mannose binding concanavalin A surfaces is used. A series of thermoresponsive glycopolymers is synthesized varying the carbohydrate type, their density, and linker type, and...

Selective Adhesion and Switchable Release of Breast Cancer Cells via Hyaluronic Acid Functionalized Dual Stimuli-Responsive Microgel Films

“…Overall, the light-triggered release was much faster and significantly more efficient when compared to the temperature-triggered release. The lower efficiency of the temperature-trigged release might be related to specific CD44–HA interactions or hysteresis effects of thermoresponsive materials hindering complete phase transition upon cooling . Similarly, successful photocleavage of polymers was applied for antimicrobial coatings, i.e., to remove bacteria from surfaces. , To the best of our knowledge, the light-triggered cleavage of the well-known adhesion motif HA was applied for the first time to facilitate the release of the cells.…”

Surface‐Bound Microgels for Separation, Sensing, and Biomedical Applications

“…The thermoresponsive folding of the PNIPAm chains enabled controlling the display of mannose, thus providing a means to control the adhesion rate of the microgels. [46] Wilms et al used similar mannose-presenting microgels to engineer reversibly bio-adhesive surfaces. Below the LCST, swollen microgels presented more uniform surfaces and a high density of mannose residues, thus providing strong cell adhesion.…”

“…Specifically, controlled swelling has been leveraged to release physically bound molecules, [20,[34][35][36] adjust the surface stiffness, [5,25,[37][38][39] and enable sensing activity. [9,40,41] Furthermore, the monomers used to construct the microgels are often amenable to post-synthetic modification with (bio)macromolecules, [42][43][44][45][46] nanoparticles, [47][48][49] and small molecules, [50][51][52][53] thus expanding their technological potential.…”

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

“…[ 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 ]…”