Promotion of neurite outgrowth by rationally designed NGF-β binding peptide nanofibers
| Autor: | Mustafa O. Guler, Canelif Yilmaz, Ayse B. Tekinay, Gulcihan Gulseren, Zeynep Okur, Busra Mammadov, Oya I Senturk |
|---|---|
| Přispěvatelé: | Güler, Mustafa O. |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
MAPK/ERK pathway
Neurite Neuronal Outgrowth Nanofibers Biomedical Engineering 02 engineering and technology Tropomyosin receptor kinase A 010402 general chemistry PC12 Cells 01 natural sciences Rats Sprague-Dawley Peptide Library Ganglia Spinal Nerve Growth Factor medicine Animals General Materials Science Amino Acid Sequence Receptor trkA Peptide library Neurons Chemistry Cell Differentiation Nerve injury 021001 nanoscience & nanotechnology Rats 0104 chemical sciences Cell biology medicine.anatomical_structure Nerve growth factor Gene Expression Regulation nervous system Nanofiber Peripheral nervous system Mitogen-Activated Protein Kinases medicine.symptom Peptides 0210 nano-technology Protein Binding |
| Zdroj: | Biomaterials Science |
| Popis: | Promotion of neurite outgrowth is an important limiting step for regeneration in nerve injury and depends strongly on the local expression of nerve growth factor (NGF). The 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. In this study, we show bioactive peptide amphiphile (PA) nanofibers capable of promoting neurite outgrowth by displaying high density binding epitopes for NGF. A 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. The bioactive nanofiber had higher affinity for NGF compared to control nanofibers and in vitro studies revealed 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 NGFB-PA nanofiber was further shown as a promising material to support axonal outgrowth from primary sensory neurons. These materials will pave the way for the development of new therapeutic agents for peripheral nervous system injuries. We would like to thank Prof. A. Arslanoglu from Izmir Institute of Technology, Izmir, Turkey, for his kind supplying of the XL1Blue bacteria strain. We would like to thank Z. Erdogan for help with LC-MS and M. Guler for TEM imaging. We also thank N. Gunduz for help with SEM imaging, M. Sever for her help with cell culture studies, and A. D. Ozkan for his valuable comments. This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) Grant Number 215S770. Z.O. was supported by a TUBITAK BIDEB 2210-C fellowship. A.B.T. acknowledges support from the Science Academy Outstanding Young Scientist Award (BAGEP). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|