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dc.rights.licenseRestricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.
dc.contributorDordick, Jonathan S.
dc.contributorKarande, Pankaj
dc.contributorShi, Sufei
dc.contributorHull, Robert, 1959-
dc.contributorStanley, Sarah
dc.contributor.authorBrier, Matthew I.
dc.date.accessioned2021-11-03T09:19:05Z
dc.date.available2021-11-03T09:19:05Z
dc.date.created2020-08-14T12:21:32Z
dc.date.issued2020-05
dc.identifier.urihttps://hdl.handle.net/20.500.13015/2548
dc.descriptionMay 2020
dc.descriptionSchool of Engineering
dc.description.abstractIn this system, ferritin, an iron sequestering protein that forms a magnetic core, acts as a transceiver by receiving magnetic field signals and transmitting them to TRPV1 to gate the flux of calcium into cells, modulate intracellular calcium-dependent signaling pathways, and stimulate cellular processes. The void in understanding lies in how ferritin gates the associated TRPV1 cation channel in the presence of magnetic fields. In this work, a potential mechanism was elucidated by exploring the three essential system components: (i) the method of magnetic stimulation, (ii) the magnetic ferritin nanoparticle, and (iii) the TRPV1 cation channel. To study magnetic stimulation of the TRPV1-ferritin platform, a number of devices were designed and constructed that produced magnetic fields with varying strengths, gradients, and oscillation frequencies. The material properties of ferritin were characterized and correlated to changes in responsiveness to magnetic stimulation as a function of in vitro growth medium composition, which is a known effector of ferritin nanoparticle composition. Similarly, responsiveness to ferritin-mediated magnetic stimulation was studied with respect to known chemical modulators of TRPV1 activation and associated calcium signaling pathways. In combination, these studies provided insights into ferritin-mediated gating of TRPV1 and resulted in a potential chemical-based mechanism of magnetogenetic control of cellular response.
dc.description.abstractUnderstanding how cells regulate physiological functions has become an area of significant interest in both the fields of bioengineering and medicine. Great strides have been made in understanding cell signaling pathways, how they regulate cell functions, and their relationship to abnormal or diseased states. Progress in these areas has led to a number of genetic platforms that can be introduced to an organism and remotely stimulated to regulate cellular processes and control cell physiology. Magnetogenetics is one such platform that has been demonstrated to remotely control intracellular signaling and gene expression in vitro and metabolism and behavior in vivo with high spatiotemporal resolution; however there remains a void in the fundamental understanding of magnetogenetic platforms. This dissertation research focused on filling this void and elucidating the mechanism of control underlying a magnetogenetic platform composed of genetically encoded magnetic nanoparticles (ferritin) conjugated to a cellular membrane calcium ion channel (transient receptor potential vanilloid 1, TRPV1).
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.subjectChemical engineering
dc.titleElucidating the mechanism of magnetogenetics
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid180138
dc.digitool.pid180139
dc.digitool.pid180140
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.degreePhD
dc.relation.departmentDept. of Chemical and Biological Engineering


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