Description
- Abstract:
- The mechanical interaction of neutrophils with the extracellular matrix (ECM) is essential in regulating neutrophil migration to sites of inflammation, a process known as chemotaxis. The vital chemotaxis response of the neutrophil becomes dysregulated in many disease states, including sepsis and certain autoimmune diseases, which can lead to increased risk of infection, organ failure, and death. Therefore, understanding the neutrophil chemotaxis response and its subsequent dysregulation in disease models from a mechanical perspective is of utmost clinical importance. Many experimental and computational challenges prevent neutrophil biologists from studying three-dimensional neutrophil force generation, including prohibitively expensive imaging equipment requirements and difficulties characterizing and modeling fibrous materials. To this end, presented here are two new methods for quantifying three-dimensional traction forces produced by neutrophils. The first is for cells crawling on planar substrates imaged using epifluorescence microscopy, an inexpensive imaging modality that historically limited users to two-dimensional traction force reconstruction. The second method is for measuring tractions from neutrophils fully embedded in fibrous ECM using a material model that can be experimentally validated and fit to fibrous hydrogel systems using the described three-dimensional material characterization technique. This technique is then applied to measure surface tractions produced by neutrophils undergoing chemotaxis in a novel chemokine gradient-producing device. These developments provide the fundamental experimental and analytical techniques required for future work probing neutrophil force generation and dysregulation.
- Notes:
- Thesis (Ph. D.)--Brown University, 2020
Citation
Hazlett, Lauren,
"Methods for Multi-Dimensional Analysis of Neutrophil Mechanosensing"
(2020).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:wfcwjhwb/
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....