Title:
Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences

dc.contributor.advisor Finn, M. G.
dc.contributor.author Bachman, Haylee N.
dc.contributor.committeeMember Williams, Loren
dc.contributor.committeeMember Barry, Bridgette
dc.contributor.committeeMember Lam, Wilbur
dc.contributor.department Chemistry and Biochemistry
dc.date.accessioned 2019-01-16T17:19:53Z
dc.date.available 2019-01-16T17:19:53Z
dc.date.created 2017-12
dc.date.issued 2017-08-28
dc.date.submitted December 2017
dc.date.updated 2019-01-16T17:19:53Z
dc.description.abstract Recombinant proteins which mimic fibronectin’s (Fn’s) integrin binding domain in conformationally stable and unfolded states are investigated to explore integrin specificity and downstream phenotypic differences on lung fibroblasts. The recombinant protein expression and purification systems are redesigned for optimization and ease of isolation. Protein purification is validated and protein function is confirmed. These recombinant proteins are then used to explore biological function such as differential integrin engagement and focal adhesion associated signaling proteins. The “integrin-switch” behavior is characterized, focal adhesion quality is investigated, and force-mediated focal adhesion components FAK and Src are observed for phosphorylation in combination with recombinant variant Fn fragments. Lung fibroblast phenotype is examined based on the conformational bias of Fn’s integrin binding domain as well. Evalutation of cell contractility is explored via cell shape and size. Cell proliferation and etabolism are assessed to determine differences based on Fn fragment conformation presentation. The myfibroblast indicator of MRTF nuclear translocation is calculated to define how myo-like lung fibroblasts are with differential integrin engagement. These findings suggest that by mimicking stable vs unfolded conformations of Fn’s IBD different integrins are engaged and downstream cell behavior is affected. There appears to be a temporal relationship between lung fibroblasts and their substrate exposure which may cause phenotype changes that lead to myofibroblast dysregulation.
dc.description.degree Ph.D.
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/60669
dc.language.iso en_US
dc.publisher Georgia Institute of Technology
dc.subject Fibronectin
dc.subject Integrin
dc.subject Mechanobiology
dc.subject Matrix biology
dc.subject Extracellular matrix
dc.title Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Finn, M. G.
local.contributor.corporatename School of Chemistry and Biochemistry
local.contributor.corporatename College of Sciences
relation.isAdvisorOfPublication f72cb35f-948e-4aa0-8856-cf62b8c2a4b7
relation.isOrgUnitOfPublication f1725b93-3ab8-4c47-a4c3-3596c03d6f1e
relation.isOrgUnitOfPublication 85042be6-2d68-4e07-b384-e1f908fae48a
thesis.degree.level Doctoral
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
BACHMAN-DISSERTATION-2017.pdf
Size:
3.07 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
LICENSE.txt
Size:
3.87 KB
Format:
Plain Text
Description: