Title Information
Title
Analysis of nanostructuredve vs Lipopolysaccharide (LPS) Activated Neutrophil Chemotaxis in 3D Collagen Matrices Using Traction Force Microscopy
Name: Personal
Name Part
Stout, David Andrew
Role
Role Term: Text
creator
Origin Information
Copyright Date
2014
Physical Description
Extent
25, 133 p.
digitalOrigin
born digital
Note
Thesis (Ph.D. -- Brown University (2014)
Name: Personal
Name Part
Franck, Christian
Role
Role Term: Text
Director
Name: Personal
Name Part
Reichner, Jonathan
Role
Role Term: Text
Reader
Name: Personal
Name Part
Tripathi, Anubhav
Role
Role Term: Text
Reader
Name: Personal
Name Part
Darling, Eric
Role
Role Term: Text
Reader
Name: Personal
Name Part
Hammer, Daniel
Role
Role Term: Text
Reader
Name: Corporate
Name Part
Brown University. Biomedical Engineering
Role
Role Term: Text
sponsor
Genre (aat)
theses
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.
Subject
Topic
Traction Force Microscopy
Subject
Topic
Neutrophil
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/853592")
Topic
Chemotaxis
Record Information
Record Content Source (marcorg)
RPB
Record Creation Date (encoding="iso8601")
20141006
Language
Language Term: Code (ISO639-2B)
eng
Language Term: Text
English
Identifier: DOI
10.7301/Z0CC0Z19
Access Condition: rights statement (href="http://rightsstatements.org/vocab/InC/1.0/")
In Copyright
Access Condition: restriction on access
Collection is open for research.
Type of Resource (primo)
dissertations