Cell-Extracellular Matrix Interactions

The extracellular matrix (ECM) contains an abundant variety of signals that are received by cell surface receptors and contribute to cell adhesion and cell fate, via regulation of cellular activities such as proliferation, migration and differentiation. As such, regenerative medicine studies often rely on mimicking the natural ECM to promote the formation of new tissue by host cells, and characterization of natural ECM components is vital for the development of new biomimetic approaches. A wide array of bioactive molecules contribute to cell-ECM interactions, including integrins, glycosaminoglycans, glycoproteins, fiber-forming elements, elastins and collagens. In our studies, we utilize synthetic peptide nanofiber systems to mimic the function of these matrix components and try to investigate extracellular matrix-cell interactions by using biofunctional nanofibers. Our group functionalizes peptide scaffolds with ligands of cell surface receptors and analyzes the effects of these interactions at a molecular level. We have also designed and synthesized peptide nanofiber systems with various functionalities, such as glycosaminoglycan mimics with growth factor binding capability, and shown that these nanofiber systems, together with other functional nanofibers, contribute to the growth and differentiation during neural differentiation, chondrogenesis and angiogenesis.

Screening of Peptide Sequences for Regenerative Medicine

Phage display is a technique that investigates the interactions between proteins, peptides and nucleic acids by engineering the natural properties of bacteriophages. Phages are bacterium-infecting viruses that direct the synthesis of proteins based on their own genetic information. This property allows the production of a specific protein or peptide on the coat protein of a genetically modified phage. The protein/peptide of interest can then be screened against a target molecule for the detection of specific interactions between biological molecules. Commercially available libraries, which contain large numbers of peptide molecules to expressed on virus surfaces, are commonly employed to find sequences that bind to a target of interest with high specificity. Our previous studies have demonstrated the importance of peptide amphiphile-growth factor interactions for the regeneration of several tissue types, such as nerve, cartilage, bone and skin. We are now employing phage libraries to better manipulate cell-peptide material interactions and further enhance the regenerative efficiency of our peptide amphiphile networks.

Selected publications:

Unal Gulsuner H, Atalay Gengec N, Kilinc M, Erbil HY, Tekinay AB., Osteoselection supported by phase separated polymer blend films, J Biomed Mater Res A., 2014 Mar 12. doi: 10.1002/jbm.a.35164.

Ceylan, H., Ozgit-Akgun, C., Erkal, T.S., Donmez, I., Garifullin, R., Tekinay, A.B., Usta, H., Biyikli, N., Guler, M. O., Size-controlled conformal nanofabrication of biotemplated three-dimensional TiO2 and ZnO nanonetworks, Scientific Reports, 2013, 3, 2306, DOI: 10.1038/srep02306.