Novel Mechanisms for Magnetogenetic Neuromodulation

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dc.contributor.advisorRobinson, Jacoben_US
dc.contributor.committeeMemberNatelson, Douglasen_US
dc.contributor.committeeMemberClementi, Ceciliaen_US
dc.contributor.committeeMemberKemere, Caleben_US
dc.creatorPolali, Sruthien_US
dc.date.accessioned2019-05-16T20:01:48Zen_US
dc.date.available2019-05-16T20:01:48Zen_US
dc.date.created2018-08en_US
dc.date.issued2017-10-24en_US
dc.date.submittedAugust 2018en_US
dc.date.updated2019-05-16T20:01:49Zen_US
dc.description.abstractMagnetogenetic tools permit wireless stimulation of specific neurons located deep inside the brain of freely moving animals: a capability that improves the study of neural activity and its correlation to behavior. Recently, a fully genetically encoded, magnetically sensitive protein chimera consisting of ferritin and TRPV4, dubbed Magneto2.0, was shown to elicit action potentials in neurons when exposed to a magnetic field. The iron-sequestering protein, ferritin serves as the magnetically sensitive domain in this chimera, while TRPV4 is a cation selective channel that responds to mechanical and temperature stimuli. While it was suggested that the mode of operation was through mechanical stimulation of the channel by ferritin, later calculations show that the forces exerted by ferritin nanoparticles are orders of magnitude lower than what is required for channel gating. We propose an alternate mechanisms based on the magnetocaloric effect to explain how paramagnetic ferritin could gate the thermally sensitive TRPV4. A magnetic field reduces the entropy of the ferritin nanoparticles when its magnetic spins align, resulting in an increase in temperature that in turn gates the heat-sensitive TRPV4 channel. We support our theory with calculations and experimental data that demonstrate that the observed responses are indeed thermally mediated. To further prove the magnetocaloric mechanism, we designed a novel magnetogenetic channel consisting of fusion of ferritin and cold-sensitive channel TRPM8, dubbed MagM8. This channel is activated due to decrease in temperature caused by increase in entropy during demagnetization of ferritin. In addition to reconciling biological observations with physical properties of genetically encoded magnetic nanoparticles, our explanation will also aid the design of new magnetogenetic tools with improved magnetic sensitivity.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationPolali, Sruthi. "Novel Mechanisms for Magnetogenetic Neuromodulation." (2017) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/105466">https://hdl.handle.net/1911/105466</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/105466en_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.subjectMagnetogeneticen_US
dc.subjectNeuromodulationen_US
dc.subjectMagnetocaloricen_US
dc.subjectMagnetic Stimulationen_US
dc.subjectTRP channelsen_US
dc.subjectFerritinen_US
dc.titleNovel Mechanisms for Magnetogenetic Neuromodulationen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentApplied Physicsen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelMastersen_US
thesis.degree.majorApplied Physics/Electrical Engen_US
thesis.degree.nameMaster of Scienceen_US
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