Thermosensitive display of ligand molecules on microgel scaffolds to facilitate switchable bioadhe-sion

• Applicant: Professor Dr. Stephan Schmidt
• Subject Area: Polymer Materials ; Biomaterials ; Preparatory and Physical Chemistry of Polymers ; Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397673471

Stimuli-responsive polymer coatings with switchable interaction to cells or pathogens are becoming increasingly important in the context of biosensing, tissue engineering, drug delivery and other areas. However, the great majority of reports in the literature describe materials that change their affinity to biological systems by switching non-specific interactions, i.e. hydrophobicity or steric repulsion upon stimuli like temperature or pH. Therefore, it is the broad aim of this project to establish "smart" microgel systems with thermosensitive display of ligand moieties to switch the specific interaction to protein receptors. Recently, we have established non-responsive hydrogel-based microgels conjugated with various ligands exhibiting highly specific interactions to protein receptors. The receptor binding affinity of such hydrogel scaffolds could be tuned by varying the multivalent display of conjugated ligands, e.g. by changing their density, linker chemistry or polymer backbone. Within this project, we now extend this approach towards microgels with poly(N-isopropylacryalamide) (PNIPAM) as responsive polymer matrix that allow changing surface area of gel particles and their ligand display by means of temperature stimulus. Furthermore, we intend to utilize the shift in hydrophobicity of PNIPAM upon temperature change to control ligand display. Therefore, case studies on biotin, mannose and hyaluronic acid as highly relevant ligand systems with varying degree of hydrophobicity will be coupled to PNIPAM microgels and their temperature dependent presentation will be tested by calorimetric receptor binding studies. In addition, the radial distribution of ligands within the microgel will be varied to form microgels with a functionalized shell and a thermosensitive core in order to improve the specificity of their interaction. Taking the temperature dependence of the microgels’ network structure into consideration, we envision surface coatings of ligand-functionalized microgels with the ability to catch and release pathogens. Therefore, the temperature dependent ligand display, microgel mechanics and bio-adhesion of the microgels will be studied via fluorescence, light scattering and force spectroscopy measurements. Finally, their ability to accumulate and release pathogens will be tested by studying the adhesion of E. coli on mannose functionalized microgel films.Overall, the microgel conjugates to be established in this proposal may represent a new way to control the activity of ligands in a polymer scaffolds by temperature stimulus. This proposal mainly focuses on fundamental questions, i.e. the overall feasibility, performance and mechanistic aspects of ligand display in responsive gels. As a first proof-of-concept application, the last part of the project will concentrate on material science aspects and application of ligand conjugated PNIPAM microgels as bioactive coating.

• DFG Programme: Research Grants