3D Cell cultures for understanding bTBI
Abstract
As protective apparel has increased in effectiveness, the injuries suffered by warfighters have changed in nature. One of the more prevalent injuries is related to the shock waves generated by explosions. While these waves damage both internal organs and the brain, the damage sustained by the brain is significantly more traumatic, both in the short and long terms. Given its high occurrence rate in soldiers, it has been termed blast induced traumatic brain injury (b-TBI). However, while there is an empirical relationship between blast exposure and brain trauma, the precise mechanism which results in the damage is not well-understood. One of the proposed mechanisms involves the concept of microbubble formation and collapse. The bubble collapse gives rise to microcavitation, which act as large internal shock waves – disrupting the cellular membrane. An alternative hypothesis is based on the concept of heat formation as the bubbles collapse. The cells respond to the higher temperatures at a molecular level, and self-destruct. Therefore, the proposed mechanisms are substantially different (cellular vs. molecular). In order to differentiate which mechanism is correct, it is necessary to independently probe both the cellular structure (morphology) and the molecular signaling of these cells. Given the dynamic nature of this response, these experiments need to be performed in real-time. However, the current methods of performing these experiments are limited to endpoint measurements. As a result, they lack the requisite capabilities to accurately probe this complex system. In the present work, we will develop an alternative method of monitoring cell behavior in 3D cultures and use it to better understand bTBI. This work contains both a sensing system development aspect and a biological systems study component. Specifically, our sensing method combines integrated optical sensors with a 3D Cell culture cube to enable real-time detection of extracellular signaling proteins. To study bTBI, this system will be integrated with an ultra-sound transducer and a carbon dioxide laser; these will enable the generation of microbubbles in the 3D cell culture chamber. We will use this system to detect the suite of signaling proteins related to heat gradients and bTBI in response to the microbubbles in real-time; thus, determining if the response is occurring at a molecular level. Additionally, real-time imaging experiments will be performed studying morphology changes of the cells in response to microbubbles; thus, determining if the response is occurring at a cellular level. Therefore, the current methods for understanding bTBI will be re-envisioned, allowing a comprehensive study of this disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 12, 2016
- Source ID
- N000141512703
Entities
People
- Andrea Armani
Organizations
- Office of Naval Research
- United States Navy
- University of Southern California