Description
- Abstract:
- Understanding the fundamental mechanisms, and forces, underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. One such disease is sepsis. During sepsis--a complex clinical syndrome that results from a harmful or damaging host response to infection--directed impairment has been shown of neutrophils to infectious foci and inadequate antimicrobial responses. In order to understand how sepsis affects neutrophil migration, we investigated the force generating characteristics and comparison between normal and septic neutrophil chemotaxis in a physiological relevant 3D mechanistically tractable system with the use of 3D FIDVC techniques. The development of a well controlled diffusion direct-viewing system was completed for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles. More compelling, we were able to successfully calculate the coefficient of diffusion of Rhodamine through five different concentrations of collagen as well as solve the governing diffusion equations to find the specific concentration along the surface of the cell. With the use of time-lapsed confocal microscopy and FIDVC we were able to probe the force generating chemotactic characteristic differences of naive and LPS activated neutrophils. We were able to show that in 3D, LPS activated neutrophils have greater deformation and displacement capabilities, while increasing their speed and decreasing their directness. Investigating the signaling pathways between fMLP and LPS our research suggests a molecule used in both GPCR and TRL4 pathways is being affected which may shed light in understanding sepsis. By introducing the study of mechanics in the investigation of sepsis, we have presented insight (force generation location and mobility) on how sepsis may alter neutrophil function that may not have been noticed by traditional biological assays.
- Notes:
- Thesis (Ph.D. -- Brown University (2014)
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Citation
Stout, David Andrew,
"Analysis of nanostructuredve vs Lipopolysaccharide (LPS) Activated Neutrophil Chemotaxis in 3D Collagen Matrices Using Traction Force Microscopy"
(2014).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0CC0Z19
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....