Browsing by Subject "Neural differentiation"

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Open Access
Cooperative effect of heparan sulfate and laminin mimetic peptide nanofibers on the promotion of neurite outgrowth
(Elsevier, 2012) Mammadov, Busra; Mammadov, Rashad; Güler, Mustafa O.; Tekinay, Ayse B.
Extracellular matrix contains an abundant variety of signals that are received by cell surface receptors contributing to cell fate, via regulation of cellular activities such as proliferation, migration and differentiation. Cues from extracellular matrix can be used for the development of materials to direct cells into their desired fate. Neural extracellular matrix (ECM) is rich in axonal growth inducer proteins, and by mimicking these permissive elements in the cellular environment, neural differentiation as well as neurite outgrowth can be induced. In this paper, we used a synthetic peptide nanofiber system that can mimic not only the activity of laminin, an axonal growth-promoting constituent of the neural ECM, but also the activity of heparan sulfate proteoglycans in order to induce neuritogenesis. Heparan sulfate mimetic groups that were utilized in our system have an affinity to growth factors and induce the neuroregenerative effect of laminin mimetic peptide nanofibers. The self-assembled peptide nanofibers with heparan sulfate mimetic and laminin-derived epitopes significantly promoted neurite outgrowth by PC-12 cells. In addition, these scaffolds were even effective in the presence of chondroitin sulfate proteoglycans (CSPGs), which are the major inhibitory components of the central nervous system. In the presence of these nanofibers, cells could overcome CSPG inhibitory effect and extend neurites on peptide nanofiber scaffolds. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Open Access
Design and application of nerve growth factor-β binding peptide nanofibers for neural regeneration
(2016-11) Orhan, Zeynep
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.