Browsing by Subject "peptide amphiphiles"

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Open Access
Characterization of peptide amphiphile nanofibers their interactions with chondroprogenitor cells and morphological analysis of tissues from transgenic animals
(2012) Tombuloğlu, Ayşegül
Peptide amphiphiles, molecules able to self assemble into three dimensional networks resembling to extracellular matrix which is excessive in cartilage tissue, are suitable candidates for overcoming cartilage tissue defects and diseases which constitute central health problems throughout ages. Understanding developmental processes that underlie cartilage formation is also key for regenerating cartilage. In this study, peptide amphiphiles were synthesized, their potential for cartilage regeneration was investigated and a model for cellular aggregation, which is a central process in embryonic cartilage development, was established with chondroprogenitor cells and peptide amphiphile scaffolds. On scaffolds, chondroprogenitor cells aggregated without requiring any additional bioactive factors as opposed to cells grown without scaffolds. Addition of insulin to the medium enhanced the size of the aggregates suggesting scaffolds may be interacting with insulin. Similar to native cartilage tissue, collagen II was massively produced in aggregates. GAG-PA which is designed to mimic glycosaminoglycans and Glu-PA which only presents glutamic acid were used to construct scaffolds with oppositely charged Lys-PA presenting lysine. Formation of aggregates was observed regardless of the PAs used. Use of both GAGPA and Glu-PA induced larger number of aggregates than only Glu-PA. Differential effect of GAG-PA couldn’t be inferred completely and might be investigated in more detail. In a second part of the study, tissue morphologies of lynx3 null mutant mice were studied. Lynx3 is a recently discovered protein belonging to Ly6-superfamily. It is expressed mainly within epithelial lining of respiratory, digestive and genital tracts and is involved in nicotinic acetylcholine receptor desensitization. In this study, morphologies of lynx3 null mice with that of wild type mice were compared to see whether lynx3 has a gross effect on the tissues in which it is expressed. Any significant difference in the morphologies of lung, trachea and thymus cannot be observed. Little variations in esophagus, stomach and female reproductive organ were seen, however, it was not clear whether these variations are related to individual differences or not and the relevance of the variations with lynx3 expression could not be seen clearly. More detailed analysis of tissues may provide additional insight to understand function of lynx3 and the cholinergic mechanisms within various tissues. Short peptides able to pass cell membrane and deliver genes into cells are outstanding alternatives to virus based transfection systems. In the third part of the study, peptide amphiphiles designed to mimic the natural polycationic proteins through forming nanofibers which exhibit positively charged residues at high density, were synthesized. Peptide amphiphiles could form stable complexes with DNA, through neutralization of charges and formation of hydrogen bonds. However, efficient transfection of the gene couldn’t be provided by any complexes in vitro. The study presents primary results upon which more detailed investigation can be built.
Open Access
Peptide nanofibers for engineering tissues and immune system
(2014) Mammadov, Rashad
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.