Influence of Fluid Dynamics on Silver Nanoparticle Behavior and Monocytic Cellular Response

Date of Award

2018

Degree Name

M.S. in Bioengineering

Department

Department of Chemical, Materials and Bioengineering

Advisor/Chair

Advisor: Kristen Comfort

Abstract

Nanoparticles (NPs) are being increasingly used in many industries and consumer products. As they become more prevalent in consumer goods and applications, a new area of study, nanotoxicology, which explores the safety of these novel materials, has emerged. The toxicity of a particular NP can be due to many tunable physicochemical properties, such as size, core composition, morphology, and surface charge. That toxicity can also be affected by the environment surrounding the NP, including whether the system is static or dynamic, if the cells are grown within a 2-dimensional or 3-dimensional space, and the composition of the surrounding fluid.Currently, most nanotoxicity testing occurs in a standard cell-based in vitro model. These models do not take the true physiological environment in which NP exposure occurs, such as pH or the dynamic nature of the human body, into account. This investigation sought to understand some of the effects, toxicological or otherwise, of silver nanoparticles (AgNPs) on the U937 monocytic cell within both a static and dynamic exposure condition. Dynamic flow was created using a peristaltic pump, operating at a flow rate to produce an average tube-side linear velocity of 0.2 cm/s; the known velocity within capillaries. As the U937 cell line grew in suspension, the cells themselves were moving with the AgNPs throughout the duration of the exposure under dynamic conditions.The addition of the fluid dynamics had minimal effect on the physicochemical properties of the AgNPs themselves. However, the interactions of the AgNPs with the cells were greatly increased with the addition of the dynamic fluid movement. This increase in nano-cellular interactions also augmented AgNP-dependent bioresponses, including reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) leakage, heat shock protein 27 (HSP27) activation, and activation of an inflammatory response.These observed alterations to cellular viability, stress, and inflammatory markers between static and dynamic exposure conditions suggest that the incorporation of physiologically relevant conditions in an in vitro model enhance the cellular model and could provide a mechanism to bridge the gap between in vitro and in vivo models.

Keywords

Biochemistry, Biomedical Engineering, Cellular Biology, Chemical Engineering, Nanotoxicity, Silver, Monocyte, Fluid dynamics, Inflammatory response

Rights Statement

Copyright © 2018, author

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