A new tool to determine the cellular metabolic landscape: nanotechnology to the study of Friedreich's ataxia.

ABSTRACT

Understanding the cell response to oxidative stress in disease is an important but difficult task. Here, we demonstrate the feasibility of using a nanomotion sensor to study the cellular metabolic landscape. This nanosensor permits the non-invasive real-time detection at the single-cell level and offers high sensitivity and time resolution. We optimised the technique to study the effects of frataxin overexpression in a cellular model of Friedreich's ataxia, a neurodegenerative disease caused by partial silencing of the FXN gene. Previous studies had demonstrated that FXN overexpression are as toxic as silencing, thus indicating the importance of a tight regulation of the frataxin levels. We probed the effects of frataxin overexpression in the presence of oxidative stress insults and measured the metabolic response by the nanosensor. We show that the nanosensor provides new detailed information on the metabolic state of the cell as a function of time, that agrees with and complements data obtained by more traditional techniques. We propose that the nanosensor can be used in the future as a new and powerful tool to study directly how drugs modulate the effects of oxidative stress on Friedreich's ataxia patients and, more in general, on other neurodegenerative processes.