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      • Graduate Program in Neuroscience - Master's degree
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      •   BUIR Home
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      • Theses - Graduate Program in Neuroscience
      • Graduate Program in Neuroscience - Master's degree
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      Design and application of nerve growth factor-β binding peptide nanofibers for neural regeneration

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      Embargo Lift Date: 2018-11-14
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      Author(s)
      Orhan, Zeynep
      Advisor
      Tekinay, Ayşe Begüm
      Date
      2016-11
      Publisher
      Bilkent University
      Language
      English
      Type
      Thesis
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      Abstract
      Promotion of neurite outgrowth is an important limiting step for the regeneration of nerve injury and depends strongly on the local expression of nerve growth factor (NGF). Rational design of bioactive materials is a promising approach for the development of novel therapeutic methods for nerve regeneration, and biomaterials capable of presenting NGF to nerve cells are especially suitable for this purpose. This thesis describes development of nanofibrous peptide amphiphile (PA) nanofibers capable of promoting neurite outgrowth by displaying high density binding epitopes for NGF. The high-affinity NGF-binding sequence was identified by phage display and combined with a beta-sheet forming motif to produce a self-assembling PA molecule. Our results revealed that the bioactive nanofiber had higher affinity for NGF compared to control nanofiber and in vitro studies showed that the NGF binding peptide amphiphile nanofibers (NGFB-PA nanofiber) significantly promote the neurite outgrowth of PC-12 cells. In addition, the nanofibers induced differentiation of PC-12 cells into neuron-like cells by enhancing NGF/high-activity NGF receptor (TrkA) interactions and activating MAPK pathway elements. The first time with this study a seven amino acid phage display peptide library was utilized for high affinity epitope screening for NGF, the NGF binding sequence was incorporated into peptide amphiphile structure, and the effect of NGF binding material on differentiation pathway of NGF was analyzed. This material will pave the way for development of new therapeutic agents for nervous system injuries.
      Keywords
      Nerve growth factor
      Epitope screening
      Phage display
      Neural differentiation
      PC-12 cells
      Peptide amphiphiles
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      http://hdl.handle.net/11693/32526
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      • Graduate Program in Neuroscience - Master's degree 38
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