Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation

Abstract Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogeneti...

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Main Authors: Yichao Yu, Christopher Payne, Nephtali Marina, Alla Korsak, Paul Southern, Ana García‐Prieto, Isabel N. Christie, Rebecca R. Baker, Elizabeth M. C. Fisher, Jack A. Wells, Tammy L. Kalber, Quentin A. Pankhurst, Alexander V. Gourine, Mark F. Lythgoe
Format: Article
Language:English
Published: Wiley 2022-02-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202104194
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author Yichao Yu
Christopher Payne
Nephtali Marina
Alla Korsak
Paul Southern
Ana García‐Prieto
Isabel N. Christie
Rebecca R. Baker
Elizabeth M. C. Fisher
Jack A. Wells
Tammy L. Kalber
Quentin A. Pankhurst
Alexander V. Gourine
Mark F. Lythgoe
author_facet Yichao Yu
Christopher Payne
Nephtali Marina
Alla Korsak
Paul Southern
Ana García‐Prieto
Isabel N. Christie
Rebecca R. Baker
Elizabeth M. C. Fisher
Jack A. Wells
Tammy L. Kalber
Quentin A. Pankhurst
Alexander V. Gourine
Mark F. Lythgoe
author_sort Yichao Yu
collection DOAJ
description Abstract Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanosensitivity of astrocytes and triggers mechanogated Ca2+ and adenosine triphosphate (ATP) signaling by applying a magnetic field to antibody‐functionalized magnetic particles that are targeted to astrocytes. Using purpose‐built magnetic devices, the mechanosensory threshold of astrocytes is determined, a sub‐micrometer particle for effective MMS is identified, the in vivo fate of the particles is established, and cardiovascular responses are induced in rats after particles are delivered to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies.
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spelling doaj.art-3d7a471dc06340348c33afdea1613ef62022-12-21T20:21:03ZengWileyAdvanced Science2198-38442022-02-0196n/an/a10.1002/advs.202104194Remote and Selective Control of Astrocytes by Magnetomechanical StimulationYichao Yu0Christopher Payne1Nephtali Marina2Alla Korsak3Paul Southern4Ana García‐Prieto5Isabel N. Christie6Rebecca R. Baker7Elizabeth M. C. Fisher8Jack A. Wells9Tammy L. Kalber10Quentin A. Pankhurst11Alexander V. Gourine12Mark F. Lythgoe13Centre for Advanced Biomedical Imaging Division of Medicine University College London 72 Huntley Street London WC1E 6DD UKCentre for Advanced Biomedical Imaging Division of Medicine University College London 72 Huntley Street London WC1E 6DD UKCentre for Cardiovascular and Metabolic Neuroscience Research Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UKCentre for Cardiovascular and Metabolic Neuroscience Research Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UKHealthcare Biomagnetics Laboratory University College London 21 Albemarle Street London W1S 4BS UKHealthcare Biomagnetics Laboratory University College London 21 Albemarle Street London W1S 4BS UKCentre for Cardiovascular and Metabolic Neuroscience Research Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UKCentre for Advanced Biomedical Imaging Division of Medicine University College London 72 Huntley Street London WC1E 6DD UKDepartment of Neuromuscular Diseases Queen Square Institute of Neurology University College London Queen Square London WC1N 3BG UKCentre for Advanced Biomedical Imaging Division of Medicine University College London 72 Huntley Street London WC1E 6DD UKCentre for Advanced Biomedical Imaging Division of Medicine University College London 72 Huntley Street London WC1E 6DD UKHealthcare Biomagnetics Laboratory University College London 21 Albemarle Street London W1S 4BS UKCentre for Cardiovascular and Metabolic Neuroscience Research Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UKCentre for Advanced Biomedical Imaging Division of Medicine University College London 72 Huntley Street London WC1E 6DD UKAbstract Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanosensitivity of astrocytes and triggers mechanogated Ca2+ and adenosine triphosphate (ATP) signaling by applying a magnetic field to antibody‐functionalized magnetic particles that are targeted to astrocytes. Using purpose‐built magnetic devices, the mechanosensory threshold of astrocytes is determined, a sub‐micrometer particle for effective MMS is identified, the in vivo fate of the particles is established, and cardiovascular responses are induced in rats after particles are delivered to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies.https://doi.org/10.1002/advs.202104194astrocytesadenosine triphosphatecalciumiron oxide particlesmagnetic actuationmagnetomechanical stimulation
spellingShingle Yichao Yu
Christopher Payne
Nephtali Marina
Alla Korsak
Paul Southern
Ana García‐Prieto
Isabel N. Christie
Rebecca R. Baker
Elizabeth M. C. Fisher
Jack A. Wells
Tammy L. Kalber
Quentin A. Pankhurst
Alexander V. Gourine
Mark F. Lythgoe
Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
Advanced Science
astrocytes
adenosine triphosphate
calcium
iron oxide particles
magnetic actuation
magnetomechanical stimulation
title Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
title_full Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
title_fullStr Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
title_full_unstemmed Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
title_short Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
title_sort remote and selective control of astrocytes by magnetomechanical stimulation
topic astrocytes
adenosine triphosphate
calcium
iron oxide particles
magnetic actuation
magnetomechanical stimulation
url https://doi.org/10.1002/advs.202104194
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