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dc.rights.licenseRestricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.
dc.contributorHirsa, Amir H.
dc.contributorUnderhill, Patrick T.
dc.contributorKane, Ravi S.
dc.contributor.authorMcBride, Samantha Ann
dc.date.accessioned2021-11-03T08:47:36Z
dc.date.available2021-11-03T08:47:36Z
dc.date.created2017-05-18T14:44:58Z
dc.date.issued2015-08
dc.identifier.urihttps://hdl.handle.net/20.500.13015/1926
dc.descriptionAugust 2015
dc.descriptionSchool of Engineering
dc.description.abstractA surprisingly large number of proteins of different shapes, sizes, and functions are capable of undergoing fibrillization transformations in which protein monomers become unstable and begin to combine in a crystalline fashion to form long, thin structures, known as amyloid fibrils. Accumulation of amyloid fibrils leads to a number of disorders, including Alzheimer’s and Parkinson’s diseases. Shearing flows and hydrophobic interfaces are ubiquitous throughout the body and known to contribute strongly to fibrillization, yet the influence of these forces on amyloid formation are not well understood. Previous investigations regarding the effect of agitation on fibrillization kinetics have failed to reach a consensus on whether the effect is due to a simple increase in mixing, alterations of protein structure caused by shear extensional forces, or a combination of shear and hydrophobic interfaces.
dc.description.abstractIn order to investigate the mechanism by which flow results in increased fibrillization kinetics, experiments were conducted using two insulin variants, human and bovine. The two molecules have similar structures but display different fibrillization kinetics when exposed to heat. The slight variations between the two molecules’ amino acid sequences result in altered protein stabilities and facilitate investigation of fibrillization mechanisms. In this work, the fibrillization kinetics of the two molecules were measured under three different perturbations: heat, hydrophobic interfaces, and shear flows. Application of a two-parameter crystallization model to fibrillization assays revealed that human and bovine insulin have altered nucleation kinetics but near-identical fibril elongation rates when exposed to both heat and to shear. Experiments probing the influence of hydrophobic interfacial area on amyloid formation demonstrated that the surface area-to-volume ratio has a noticeable impact on fibrillization kinetics, and that human insulin is more responsive to varying hydrophobic surfaces. Under shear flows human and bovine insulin both exhibit peak nucleation kinetics at intermediate shear rates, while the kinetics of elongation increase monotonically with shear. This suggests that the influence of shear flow on nucleation is not a simple relationship, but that enhanced elongation rates are due to increases in mixing.
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.subjectChemical engineering
dc.titleEffect of hydrophobic residues on amyloid formation under steady shear and at interfaces
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid178122
dc.digitool.pid178123
dc.digitool.pid178124
dc.rights.holderThis electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
dc.description.degreeMS
dc.relation.departmentDept. of Chemical and Biological Engineering


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