Paper BI-WeM8
Controlled Peptide Surfaces of Various Ratios that Guide Neural Stem Cell Differentiation.
Wednesday, December 14, 2016, 10:20 am, Room Milo
Session: |
Biomolecule/Material Interactions |
Presenter: |
HalaShakib Dhowre, University of Nottingham, UK |
Authors: |
M. Zelzer, University of Nottingham, UK H.S. Dhowre, University of Nottingham, UK C. Towlson, University of Nottingham, UK HS. Sahaf, University of Nottingham, UK N.A. Russell, University of Nottingham, UK |
Correspondent: |
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Cell instructive biointerfaces represent an essential aspect for the advancement of regenerative medicine. Currently, a major issue in biointerface design is the limited ability to mimic the complex interactions of the natural processes in the extracellular matrix (ECM) with artificially designed surfaces and interfaces 1. While biomaterial surfaces have been shown to be able to elicit specific cell responses (e.g. adhesion, proliferation, differentiation), precise control akin to that of natural cellular environments is still lacking2.
AIM:
The present work aims to address this challenge by designing new synthetic peptide surfaces with well controlled composition and functionality able to impact control over the differentiation of neuronal stem cells with the ultimate goal to understand and control how neuronal networks function.
METHODS:
Compositionally well defined surface concentrations of two short laminin peptide sequences, Arg-Gly-Asp (RGD) and Ile-Lys-Val-Ala-Val (IKVAV) were prepared of various ratios via the “grafting from” stepwise approach and the surface modification was confirmed with surface analysis techniques to indicate successful peptide functionalisation. The neural stem and progenitor cells (NSPC) were set up from embryonic rat hippocampi (E18). Immunocytochemistry (ICC) observed cell viability and differentiation to specific NSPC lineages for Nestin, βIII-Tubulin and GFAP.
RESULTS:
Surface characterising techniques (WCA, AFM and ToF-SIMS) verified the successful amino acid build-up to peptides on the surfaces, allowing modification of the surfaces with RGD and IKVAV. Enhanced NSPC adhesion, proliferation and differentiation were observed on the peptide surfaces. ICC demonstrated Nestin expression decrease after the removal of the growth factors (EGF and FGF) and an increase in the expression of βIII-Tubulin and GFAP; thus illustrating cells differentiating from stem cells to neurons or astrocytes due to peptide surface influence.
CONCLUSION:
Well defined peptide surfaces were designed successfully, the various ratios of RGD and IKVAV surfaces demonstrated cell adhesion, proliferation and influences desirable effects in controlling different populations of stem cell fate. These surfaces may advance new insight in understanding how surface properties affect the regulation of physiological relevance in directing neural cell differentiation, which will be essential to understand how neural networks function.
References
1. Zelzer, M. & Ulijn, R.V., Chem.Soc.Rev., 39,3351-3357 (2010)
2. Ricoult, S.G. et al., Biomaterials., 35, 727-736 (2014)
3. Cooke, M.J. et al., J.Biomed.Mater.Res-Part A., 93,824-832 (2010)