- Title Information
- Title
- Methods for Multi-Dimensional Analysis of Neutrophil Mechanosensing
- Name:
Personal
- Name Part
- Hazlett, Lauren
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Franck, Christian
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Reichner, Jonathan
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Hoffman-Kim, Diane
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Wong, Ian
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Nett, Jeniel
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biomedical Engineering
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2020
- Physical Description
- Extent
- xx, 113 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Ph. D.)--Brown University, 2020
- Genre (aat)
- theses
- 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.
- Subject
- Topic
- traction force microscopy
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01036683")
- Topic
- Neutrophils
- Subject
- Topic
- mechanobiology
- Subject
- Topic
- epifluorescence microscopy
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01028963")
- Topic
- Multiphoton excitation microscopy
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20210607
- Type of Resource (primo)
- dissertations