Novel Mechanisms for Magnetogenetic Neuromodulation

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dc.contributor.advisorRobinson, Jacob
dc.contributor.committeeMemberNatelson, Douglas
dc.contributor.committeeMemberClementi, Cecilia
dc.contributor.committeeMemberKemere, Caleb
dc.creatorPolali, Sruthi
dc.date.accessioned2019-05-16T20:01:48Z
dc.date.available2019-05-16T20:01:48Z
dc.date.created2018-08
dc.date.issued2017-10-24
dc.date.submittedAugust 2018
dc.date.updated2019-05-16T20:01:49Z
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.
dc.format.mimetypeapplication/pdf
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>.
dc.identifier.urihttps://hdl.handle.net/1911/105466
dc.language.isoeng
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.
dc.subjectMagnetogenetic
dc.subjectNeuromodulation
dc.subjectMagnetocaloric
dc.subjectMagnetic Stimulation
dc.subjectTRP channels
dc.subjectFerritin
dc.titleNovel Mechanisms for Magnetogenetic Neuromodulation
dc.typeThesis
dc.type.materialText
thesis.degree.departmentApplied Physics
thesis.degree.disciplineNatural Sciences
thesis.degree.grantorRice University
thesis.degree.levelMasters
thesis.degree.majorApplied Physics/Electrical Eng
thesis.degree.nameMaster of Science
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