Show simple item record

dc.contributor.advisorElazer R. Edelman.en_US
dc.contributor.authorMurikipudi, Sylajaen_US
dc.contributor.otherHarvard--MIT Program in Health Sciences and Technology.en_US
dc.date.accessioned2014-03-19T15:45:53Z
dc.date.available2014-03-19T15:45:53Z
dc.date.issued2010en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/85795
dc.descriptionThesis: Ph. D. in Materials Science and Medical Engineering, Harvard-MIT Program in Health Sciences and Technology, February 2010.en_US
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references (pages 135-139).en_US
dc.description.abstractEndothelial cells (EC) are ubiquitous - as vascular epithelial cells they line the inner surface of all vessels and are the contact surface with flowing blood. Macrovascular EC are the first line barrier between flowing blood and mural structures. The microvasculature includes EC-lined vessels that contact virtually every cell in the body. These EC are potent bioregulatory cells, modulating thrombosis, inflammation and control over mural smooth muscle cells and vascular health. The biochemical roles of EC can be retained when cells are embedded within three-dimensional matrices without recapitulation of the full vessel architecture. Within these matrices, surface and structural properties impose a set of forces on the embedded EC. Indeed, substrata pore size and modulus have profound effects on phenotype and function of a range of cell types. In the first part of this work, we examined the effect of pore size, matrix relative density and modulus on matrix-embedded EC growth and secretion and found a greater biological dependence on modulus than pore size or density. In the second part of this work, we examined the effect of isolated changes in modulus on BC growth, secretion of growth regulators, and modulation of smooth muscle cell growth. EC growth is maximal at intermediate moduli over a range from 50 Pa- 1500 Pa. Secretion of heparan sulfate proteoglycans (HSPGs), which inhibit smooth muscle cell growth, is maximal at low moduli and flat at high moduli. Secretion of growth factors such as FGF2 and PDGF-BB were also modulus responsive. Inhibition of smooth muscle cell growth rose as modulus decreased from 510 Pa to 50 Pa and was the result of a balance between increased HSPG secretion and reduced secretion of vasoactive growth factors. Changes in endothelial function correlated with extracellular matrix gene and integrin aP 3 and c41 expression. Changes in the forces experienced by the cell - a change in substrate modulus - cause the cell to alter its ECM and integrin expression in an effort to return the force balance to normal, leading to downstream effects on cell function. While growth stimulatory function largely conserved, growth inhibitory function was altered to a much larger degree. In the final part of this work, we examined the effect of scaffold modulus on EC response to inflammatory stimuli, and attempted to correlate it to changes in smooth muscle cell regulation and integrin expression. While cytokine secretion was independent of modulus, surface expression of ICAM- 1 and VCAM-1, and induction of CD4' T cell proliferation followed a similar pattern to smooth muscle cell inhibition, suggesting that similar mechanisms may be involved in their regulation by substrate modulus. Alteration of scaffold modulus has a profound impact on EC function including growth regulation and inflammatory response. The model offered in this thesis - wherein EC attempt to neutralize changes in environmental force balance by altering ECM and integrin expression, leading to changes in downstream function - offers insight into how environmental changes effect functional changes in ECs.en_US
dc.description.statementofresponsibilityby Sylaja Murikipudi.en_US
dc.format.extent139 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectHarvard--MIT Program in Health Sciences and Technology.en_US
dc.titleThe effect of scaffold physical properties on endothelial cell functionen_US
dc.typeThesisen_US
dc.description.degreePh. D. in Materials Science and Medical Engineeringen_US
dc.contributor.departmentHarvard--MIT Program in Health Sciences and Technology.en_US
dc.identifier.oclc871687841en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record