Characterization of peptide amphiphile nanofibers their interactions with chondroprogenitor cells and morphological analysis of tissues from transgenic animals
Tekinay, Ayşe Begüm
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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.
cell penetrating peptides