Responsive biohybrid microgels

Hydrogel particles with dimensions in the submicron and nanometer range, so called microgels, are a fastly developing class of biocompatible materials that are well suited as nanotechnological tools for biomedical applications. In the current project a new type of polymer biohybrid microgels with incorporated structural peptide motifs is proposed as a novel class of biomaterials. Protein folding motifs offer enormous possibilities as tools to control structure formation of synthetic polymers and due to their folding specificity, they are ideally suited to direct the self-assembly of synthetic polymers. The peptide tertiary structural motif that will be explored in this proposal is the so called coiled coil motif, a superhelical assembly of two or more helical peptides, and the objective of this work is to explore the feasibility of this peptide motif as a noncovalent crosslinker for the fabrication of biohybrid microgels. One of the unique characteristics of the coiled coil motif as noncovalent crosslinker is that its folding/unfolding behaviour can be adjusted via modification of the amino acid sequence of the peptide and the rationale behind this project is that the reversible folding/unfolding of the peptide crosslinker can be finally used to control the volume/phase transition behaviour of the microgel particles. A major part of this project aims on the development of inverse, particle forming emulsion polymerization processes, which allow the direct copolymerization of polymerizable, synthetic coiled coil peptides and a biocompatible hydrophilic monomer for the synthesis of biohybrid microgels in a one-step batch reaction. This approach has major advantages over existing processes which often require subsequent modification reactions for the incorporation of biological motives in the polymer backbone. In the last phase of this project the switchability of the microgels and its applicability as a carrier for therapeutic peptide drugs will be tested. For this purpose methods for the incorporation of peptides and proteins (BSA, Insulin) in the microgels will be developed and the release of these molecules to the environment under physiologically relevant conditions and phemperature changes will be investigated. The novelty of the current project lies in the non-reported usage of structural protein folding motifs for the production of responsive microgels and the direct one-step synthesis of these particles via inverse heterogeneous copolymerization of functionalized "coiled coil"-peptides. Due to the applicability of the resulting particles as potential drug-carriers for drug administration the project is practical in a biomedical context, and the results shall contribute to the development of the scientific fields of bioinspired/biobybrid hybrid materials in Austria.