Projects Design of Structured Adhesion Miniproteins for Tissue Engineering
Tissue Engineering requires artificial constructs to support the formation of tissue from cells. These support structures consist of microporous organic or inorganic material that immobilizes the cells of interest.
There are two common strategies for functionalizing materials for tissue engineering: the immobilization of cell adhesion motifs that bind to cell receptors or the immobilization of entire domains of cell-binding proteins. However, the small motifs lack a defined three-dimensional structure and thus bioactivity, and the large fragments are difficult to immobilize and often denature in the attempt. This project aims to unify the bioactivity of a cell binding protein with the chemical modifiability of cell adhesion motifs: the design of adhesion miniproteins based on independently folding peptide scaffolds with a cell-binding active site.
Extracellular matrix proteins are known to bind the carbohydrate chains of cell receptors with an often calcium-dependent protein-carbohydrate binding site. These active sites, located on e.g. LG domains or lectins, serve as ideal natural models for peptide design. The active site of the natural model protein is “printed” onto a β-sheet peptide scaffold, such as the SH3 or WW domain, using computational modelling to ensure similar-to-native folding. Suitable sequences are then synthesized by solid-phase peptide synthesis (SPPS) and characterized with respect to structure and binding. A sufficiently biomimetic miniprotein is planned to be immobilized on materials to add cell responsiveness and thus generate a functionalized material for retina tissue engineering.
