Mechanical impact and the resulting acceleration-induced pressure gradient on the human body is one of the main mechanisms for traumatic injury. Fundamental understanding of injury mechanisms associated with mechanical impact is essential toward the development of reliable injury criteria and more accurate prediction of injury. In addition, such knowledge could pave the way for innovative protective equipment designs and effective strategies for post-injury treatment.Here, we present a novel platform capable of applying well-characterized and reproducible acceleration-induced pressure gradients that is compatible with long-term and environmentally controlled live-cell microscopy. This in vitro platform allows close monitoring of multiple cell populations, down to individual cells, to deduce how impact effects cell viability and mitosis, as well as assays for investigating the molecular mechanisms of cell injury, such as membrane permeabilization due to pressure gradients.Our drop tower studies using the cell culture setup in vitro reveal that even a seemingly very large acceleration (~1000g) does not result in apparent cell damage due to the small size (e.g., height) of the cell culture setup (~10 mm). This result indeed emphasizes the importance of appropriately considering the effect of biological system size, in addition to acceleration, for accurate assessment of blunt injury. As an example, human head size could be an important factor to predict blunt head injury among different sample populations, e.g., female vs male or child vs adult, for a given acceleration.In addition, we show that sudden cell death is triggered by the onset of cavitation bubbles, which apply localized compressive/tensile pressure cycles to cells, in the culture chamber. We find the cavitation-induced pressure is much more violent than acceleration-induced pressure due to a very rapid rate of pressure changes in time and large pressure amplitudes relative to when no cavitation is present.This platform offers a novel window into fundamental mechanisms of cell injury due to impact. The integration with standard cell culture platforms allows future work to address fundamental questions such as: how does impact affect cell adhesion, motility, and mitosis? Indeed, novel migration or adhesion assays conducted on standard cell culture dishes could be incorporated into the in vitro impact tower set up described here. Furthermore, this platform could be expanded to a plethora of cell lines, such as neurons, or in vitro conditions, such as serum free media or altered substrate stiffness. This innovative technique may lead to new findings on impact-induced cellular pathways associated with uncontrolled cell death (e.g., necrosis and apoptosis). Such findings will pave the way for innovative technical advances in designing effective protective equipment and new biomedical technology for post-injury treatment.

Mechanisms of Cell Damage Due to Mechanical Impact – an in Vitro Investigation

Paper Proceedings: https://asmedigitalcollection.asme.org/IMECE/IMECE2021/volume/85543

ASME 2021 International Mechanical Engineering Congress and Exposition (IMECE2021)

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