Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells

Abstract The axon regeneration of neurons in the brain can be enhanced by activating intracellular signaling pathways such as those triggered by the membrane-anchored Rat sarcoma (RAS) proto-oncogene. Here we demonstrate the induction of neurite growth by expressing tagged permanently active Harvey-...

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Autores principales:	Fabian Raudzus, Hendrik Schöneborn, Sebastian Neumann, Emilie Secret, Aude Michel, Jérome Fresnais, Oliver Brylski, Christine Ménager, Jean-Michel Siaugue, Rolf Heumann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/469834a1376b4864b8dbf490c4de69c9
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spelling	oai:doaj.org-article:469834a1376b4864b8dbf490c4de69c92021-12-02T14:01:28ZMagnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells10.1038/s41598-020-80253-w2045-2322https://doaj.org/article/469834a1376b4864b8dbf490c4de69c92020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80253-whttps://doaj.org/toc/2045-2322Abstract The axon regeneration of neurons in the brain can be enhanced by activating intracellular signaling pathways such as those triggered by the membrane-anchored Rat sarcoma (RAS) proto-oncogene. Here we demonstrate the induction of neurite growth by expressing tagged permanently active Harvey-RAS protein or the RAS-activating catalytic domain of the guanine nucleotide exchange factor (SOS1cat), in secondary dopaminergic cells. Due to the tag, the expressed fusion protein is captured by functionalized magnetic nanoparticles in the cytoplasm of the cell. We use magnetic tips for remote translocation of the SOS1cat-loaded magnetic nanoparticles from the cytoplasm towards the inner face of the plasma membrane where the endogenous Harvey-RAS protein is located. Furthermore, we show the magnetic transport of SOS1cat-bound nanoparticles from the cytoplasm into the neurite until they accumulate at its tip on a time scale of minutes. In order to scale-up from single cells, we show the cytoplasmic delivery of the magnetic nanoparticles into large numbers of cells without changing the cellular response to nerve growth factor. These results will serve as an initial step to develop tools for refining cell replacement therapies based on grafted human induced dopaminergic neurons loaded with functionalized magnetic nanoparticles in Parkinson model systems.Fabian RaudzusHendrik SchönebornSebastian NeumannEmilie SecretAude MichelJérome FresnaisOliver BrylskiChristine MénagerJean-Michel SiaugueRolf HeumannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fabian Raudzus Hendrik Schöneborn Sebastian Neumann Emilie Secret Aude Michel Jérome Fresnais Oliver Brylski Christine Ménager Jean-Michel Siaugue Rolf Heumann Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells
description	Abstract The axon regeneration of neurons in the brain can be enhanced by activating intracellular signaling pathways such as those triggered by the membrane-anchored Rat sarcoma (RAS) proto-oncogene. Here we demonstrate the induction of neurite growth by expressing tagged permanently active Harvey-RAS protein or the RAS-activating catalytic domain of the guanine nucleotide exchange factor (SOS1cat), in secondary dopaminergic cells. Due to the tag, the expressed fusion protein is captured by functionalized magnetic nanoparticles in the cytoplasm of the cell. We use magnetic tips for remote translocation of the SOS1cat-loaded magnetic nanoparticles from the cytoplasm towards the inner face of the plasma membrane where the endogenous Harvey-RAS protein is located. Furthermore, we show the magnetic transport of SOS1cat-bound nanoparticles from the cytoplasm into the neurite until they accumulate at its tip on a time scale of minutes. In order to scale-up from single cells, we show the cytoplasmic delivery of the magnetic nanoparticles into large numbers of cells without changing the cellular response to nerve growth factor. These results will serve as an initial step to develop tools for refining cell replacement therapies based on grafted human induced dopaminergic neurons loaded with functionalized magnetic nanoparticles in Parkinson model systems.
format	article
author	Fabian Raudzus Hendrik Schöneborn Sebastian Neumann Emilie Secret Aude Michel Jérome Fresnais Oliver Brylski Christine Ménager Jean-Michel Siaugue Rolf Heumann
author_facet	Fabian Raudzus Hendrik Schöneborn Sebastian Neumann Emilie Secret Aude Michel Jérome Fresnais Oliver Brylski Christine Ménager Jean-Michel Siaugue Rolf Heumann
author_sort	Fabian Raudzus
title	Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells
title_short	Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells
title_full	Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells
title_fullStr	Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells
title_full_unstemmed	Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells
title_sort	magnetic spatiotemporal control of sos1 coupled nanoparticles for guided neurite growth in dopaminergic single cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/469834a1376b4864b8dbf490c4de69c9
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Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells

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