Effects of dynamic mechanical stresses on mammalian cell metabolism

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dc.contributor.advisorMcIntire, Larry V.en_US
dc.creatorRajagopalan, Sridharen_US
dc.date.accessioned2009-06-04T00:30:02Zen_US
dc.date.available2009-06-04T00:30:02Zen_US
dc.date.issued1991en_US
dc.description.abstractThe effects of dynamic mechanical stresses on the arachidonic acid (AA) metabolism of human platelets and on the cell growth properties of murine tumor cells were studied. The cells were stressed by suspending them in laminar simple shear flows. Washed human platelet suspensions were stressed at 75 dynes/cm$\sp2$ and 150 dynes/cm$\sp2$ for 5 to 10 min. at 25$\sp\circ$C. The stress stimulated AA metabolism above basal levels. The lipoxygenase metabolite 12-hydroxyeicosatetraenoic acid was preferentially formed, but the cyclooxygenase metabolite thromboxane B$\sb2$ was not detected. Thrombin-stimulated platelets, however, formed cyclooxygenase metabolites in addition to the lipoxygenase metabolites. This result indicates that the physical stresses and chemical agonists (like thrombin) affect platelet AA metabolism differently. Stress effects on tumor cells were studied using high and low metastatic sub-lines of the B16 melanoma and the RAW117 large cell lymphoma. The cells were stressed at 0, 450 and 900 dynes/cm$\sp2$ at 37$\sp\circ$C for 5 min. Damage caused by the stresses was determined by measuring the lysis in the shear field and measuring the relative reduction in cell numbers in stressed cultures compared to unstressed controls. Also, cell growth and lysis in stressed and unstressed cultures were monitored over time. The results could by modeled assuming that a subpopulation of stressed cells was lethally damaged and ultimately died while a second group of stressed cells were only sublethally damaged and grew normally after a brief lag-time. The data indicate that there was not much difference in the damage levels between high and low metastatic sub-lines and that a considerable fraction of stressed cells were not lethally damaged even at bulk shear stresses as high as 900 dynes/cm$\sp2$ for 5 min. Although the stresses applied were higher than normally seen in vivo, the results are in contrast to the accepted view that mechanical stresses developed in the circulation directly cause the destruction of most of the tumor cells during blood-borne metastasis and that highly metastatic cells can resist these stresses more effectively than poorly metastatic cells.en_US
dc.format.extent189 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoThesis Ch.E. 1990 Rajagopalanen_US
dc.identifier.citationRajagopalan, Sridhar. "Effects of dynamic mechanical stresses on mammalian cell metabolism." (1991) Diss., Rice University. <a href="https://hdl.handle.net/1911/16477">https://hdl.handle.net/1911/16477</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/16477en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectChemical engineeringen_US
dc.subjectBiophysicsen_US
dc.titleEffects of dynamic mechanical stresses on mammalian cell metabolismen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemical Engineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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