Peptide nanofibers for engineering tissues and immune system

Abstract

Interdisciplinary work at the interface of biology and materials science is important for finding cures to complex diseases. Achievements in materials science allow us to control materials at nanoscale and design them according to specific therapeutic purposes. This includes incorporating biophysical and biochemical signals into materials to make them biologically functional. These signals are sensed by cells in normal or pathological cases and influence their decision-making process, which eventually alters cellular behavior. However, cellular environment is so complex in terms of these signals that recapitulating it with synthetic materials is unattainable considering our limited resources. Therefore, we need to distinguish those signals that are structurally simple, but at the same time biologically critical, that would drive cellular behavior to desired outcome. In this thesis, I will describe peptide nanofiber systems for tissue engineering and vaccinology applications. First system is inspired from heparan sulfate (HS) – a natural polymer in extracellular matrix – that bind to growth factors and regulate their functioning, therefore central for induction of various physiological processes. Peptide nanofibers with right composition of bioactive chemical functional groups from HS showed specific interaction with growth factors and induced endothelial cells to form blood vessels similar to natural matrices carrying HS. Considering mentioned features, these peptide nanofibers could be useful for effective regeneration of tissues. Secondly, the peptide nanofiber system carrying pathogenic DNA motives, which is an infection signal, was developed. While non-immunogenic by itself, these nanofibers shifted immune response against pathogenic DNA towards a context that is useful for fighting intracellular pathogens and cancer. Overall, this thesis demonstrates that structurally simple but appropriate biophysical and biochemical signals could be synergistic for inducing desired biological processes at the nanoscale.