dc.description.abstract
Peptides, as natural and highly specific and biocompatible substrates, fibers or active compounds, are developed since their first descriptions by Crick, Corey and Pauling in the 1950’s. Inside this diverse field, coiled-coil peptides have been increasingly investigated as suitable substrates due to their self-assembly properties, which enable multivalent ligand presentation.
This thesis has the aim to develop various highly specific and stable coiled-coil peptides as possible 2D or 3D scaffolds for stem cell differentiation. Related to the up to date research in the field of cell culture materials for biological and “created by extracted own cells” implants for the human body, the goal is to direct the stem cell fate to the specific cell type needed e.g. as heart muscle tissue. Therefore, a library of different undecorated peptides was synthesized and their properties were compared to known standards. Furthermore, their impact on self-assembly and formation of stable hydrogels had to be evaluated as possible 2D or 3D scaffolds. With regard to the information, a hydrogelating fiber forming coiled-coil peptide (hFF03-bAcA) was chosen and functionalized by conjugation with biologically relevant ligands. Due to varying the density and ligands presented, the structural and mechanical properties could be adjusted. Combining all these parameters, two main applications for testing the designed peptide as suitable biomaterial were developed.
On the one hand, hFF03-bAcA presenting biological relevant ligands was tested as a tailored artificial 3D material to mimic the so-called extracellular matrix (ECM). Therefore, the system was either functionalized with carbohydrates or peptide-epitopes as signal molecules and mixed with each other in different ratios. The aim was to create a suitable 3D scaffold, which presents the desired signal molecules in a multivalent fashion. Structural and rheological characterizations revealed that the coiled-coil systems build fibrous networks with viscoelastic properties. Moreover, embryonic mouse fibroblast populations showed excellent viability profiles, when cultured on these peptide hydrogels.
On the other hand, peptide-carbohydrate conjugates were evaluated as potential inhibitors for Influenza A Virus. Therefore, sialic-acid was conjugated to fiber forming coiled-coil peptides and tested regarding density of ligands and suitability as substrates for virus inhibition. Hemagglutination-inhibition tests showed that sialic-acid conjugated coiled-coil peptides enable inhibition of Influenza A Virus in the micromolar range and are therefore promising substrates as diagnostic tool or anti-influenza drugs. In conclusion, the developed and established approaches represent a simple and efficient methodology to design 3D scaffolds based on coiled-coil peptide structures presenting in a defined and exactly adjustable density of biologically active ligands for specialized applications in the fields of tissue engineering, regenerative medicine and infectious diseases, like growing implants out of extracted steam cells.
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