(Invited) Carbon Nanotubes and Cellular Perturbation:  Augmentation of Differentiation Dynamics in Neural Stem Cells

Abstract

Delivery of materials, such as drug compounds or imaging agents for treatment or diagnosis of disease still presents a biomedical challenge. Nanotechnological advances have presented biomedicine with a number of agents that possess the appropriate size and chemistry to pass through the blood brain barrier. Functionalized carbon nanotubes are one such agent, which can potentially aid in drug and gene delivery to the central nervous system. In addition, carbon nanotubes have already been applied in several areas of nerve tissue engineering to probe and augment cell behavior, to label and track subcellular components, and to study the growth and organization of neural networks. Although the production of functionalized carbon nanotubes has escalated in recent years, knowledge of cellular changes associated with exposure to these materials remains unclear. Thus, it is crucial to develop an understanding of the effects and interactions that carbon nanotubes can induce in a living system. In this study, carbon nanotubes, wrapped with either GT20 DNA or yeast tRNA were introduced to neural stem cells during proliferation and differentiation, at doses determined to be non-lethal. At non-lethal doses, cell fate can be dramatically impacted by the carbon nanotube materials. Depending upon the mode of exposure, the differentiation dynamics are significantly altered, leading to at least a one-fold increase in the final percent of neurons in the total population. This increase in neuronal population is mathematically correlated to a change in the division symmetry of the dividing cells early in the differentiation process. In addition, the results demonstrate that the irregular patterns of cell fate are due to a variety of biophysical inputs stimulated by the carbon nanotubes, including, but not limited to, cytoskeletal perturbation, focal adhesion augmentation, and subcellular localization of the nanomaterials. Acknowledgment: NSF ECCS-1509786.