Date

2015

Document Type

Dissertation

Degree

Doctor of Philosophy

Department

Physics

First Adviser

Rotkin, Slava V.

Other advisers/committee members

Jedlicka, Sabrina; Biaggio, Ivan; Ou-Yang, Daniel; Vavylonis, Dimitrios

Abstract

Single-walled carbon nanotube based materials possess unique physical properties which can be used in the biomedical and therapeutical applications. For example, biocompatible nanotubes can serve as an optical imaging tool, for use in vitro and in vivo. Several groups, including us, demonstrated that individualized nanotubes, at low concentration (quantification of this criterion has been done in this work), have no apparent cytotoxicity to cells. However, their long-term influence on cellular structures and activities have to be investigated.Our focus is on the interaction between a specific cell type, neural stem cells, and nanotubes. It is reported here that the internalized nanotubes at therapeutical concentrations can still vary the cell behavior substantially, which is of significant interest for both a fundamental biophysics and an applied bioengineering. In particular, in this work carbon nanotubes have been shown to serve as a mediator for neuronal differentiation. This effect has not been previously experimentally observed or theoretically investigated.Traditionally, research on the implantation of neural stem cells to integrate into existing circuitry and replace damaged cell populations has focused on trying to control cellular differentiation through the use of external cues. Such perturbations cause the cells to alter their structure to adapt to their surrounding and could promote a certain line of differentiation. In this study, we took a different approach by using the nanotubes as internal cues to affect the cell response.The internalization of biofunctionalized single-wall carbon nanotubes at properly chosen concentrations (1-10 pM) by neural stem cells (C17.2) has been studied. The results of our study suggest that the tubes mediate the neuronal differentiation of C17.2 cells. They are also shown here to give rise to development of a cell type not typically observed in the C17.2 cell line. Changing the wrapping of the carbon nanotubes from a specific non-biological ssDNA ($(GT)_{20}$) to a natural tRNA did not deter the mediating effect, allowing to identify the carbon nanotubes as being solely responsible for stimulating neuronal differentiation.In trying to understand the mechanisms behind the change of cell behavior observed during this stimulated differentiation, we focused on the dynamics of the asymmetric cell division. The latter gives rise to the diversity in the final population of cells. A complex dynamics has been observed, dependent on details of nanotube intervention. Disruption of the cytoskeleton fibers, such as actin and nestin, when carbon nanotubes were added has been also observed in neural stem cells. These results are worth considering when developing physical models for neural stem cell engineering and, ultimately the strategies to neurodegeneration recovery therapies.

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