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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp018k71nm45z
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dc.contributor.advisorNelson, Celeste M-
dc.contributor.authorKlimek, Jake-
dc.date.accessioned2024-07-22T20:06:18Z-
dc.date.created2024-05-08-
dc.date.issued2024-07-22-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/dsp018k71nm45z-
dc.description.abstractAirway morphogenesis in the developing mammalian lung is coordinated by biochemical and mechanical signaling, but the physical mechanisms by which branches of the airway epithelium elongate remain unclear. Located at focal adhesions, focal adhesion kinase (FAK) is a signaling protein that integrates mechanical stimuli to control cell motility. Here, we examine the role of FAK in airway morphogenesis in order to better understand the mechanical conditions that promote epithelial branch elongation. We found that culturing lung explants in the presence of FAK inhibitor disrupted branching morphogenesis, resulting in lungs with fewer and longer branches. We did not observe changes in cell proliferation at elongating tips of branches following inhibition of FAK, suggesting that FAK co-ordinates branch morphology primarily on the tissue scale. We therefore examined the patterning of airway smooth muscle (ASM) and basement membrane components around branches following FAK inhibition. We observed increased ASM wrapping in branches treated with FAK inhibitor. Additionally, we found that FAK signaling may pattern the distribution of collagen IV in the basement membrane to regulate local tissue mechanics. With this in mind, we injected fluorescent beads into mesenchymal tissue and tracked their displacement during live organ culture. Our preliminary results suggest that mesenchymal tissue between elongating branches may be relatively fluid-like. Together, our findings re-veal a coordinated mechanical model for elongation of the airway epithelium that is in part regulated by FAK signaling. Our work therefore represents a step toward understanding the interplay between biochemical and mechanical signals that control the development of embryonic tissues.en_US
dc.format.mimetypeapplication/pdf
dc.language.isoenen_US
dc.titleTissue Sculpture: A Mechanical Basis for Elongation of the Airway Epithelium in the Developing Mammalian Lungen_US
dc.typePrinceton University Senior Theses
pu.embargo.lift2026-07-01-
pu.embargo.terms2026-07-01-
pu.date.classyear2024en_US
pu.departmentChemical and Biological Engineeringen_US
pu.pdf.coverpageSeniorThesisCoverPage
pu.contributor.authorid920245386
pu.certificateEngineering Biology Programen_US
pu.mudd.walkinNoen_US
Appears in Collections:Chemical and Biological Engineering, 1931-2024

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