Nanodelivery of a functional membrane receptor to manipulate cellular phenotype

Abstract Modification of membrane receptor makeup is one of the most efficient ways to control input-output signals but is usually achieved by expressing DNA or RNA-encoded proteins or by using other genome-editing methods, which can be technically challenging and produce unwanted side effects. Here...

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Main Authors: Tommaso Patriarchi, Ao Shen, Wei He, Mo Baikoghli, R. Holland Cheng, Yang K. Xiang, Matthew A. Coleman, Lin Tian
Format: Article
Language:English
Published: Nature Portfolio 2018-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-018-21863-3
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author Tommaso Patriarchi
Ao Shen
Wei He
Mo Baikoghli
R. Holland Cheng
Yang K. Xiang
Matthew A. Coleman
Lin Tian
author_facet Tommaso Patriarchi
Ao Shen
Wei He
Mo Baikoghli
R. Holland Cheng
Yang K. Xiang
Matthew A. Coleman
Lin Tian
author_sort Tommaso Patriarchi
collection DOAJ
description Abstract Modification of membrane receptor makeup is one of the most efficient ways to control input-output signals but is usually achieved by expressing DNA or RNA-encoded proteins or by using other genome-editing methods, which can be technically challenging and produce unwanted side effects. Here we develop and validate a nanodelivery approach to transfer in vitro synthesized, functional membrane receptors into the plasma membrane of living cells. Using β2-adrenergic receptor (β2AR), a prototypical G-protein coupled receptor, as an example, we demonstrated efficient incorporation of a full-length β2AR into a variety of mammalian cells, which imparts pharmacologic control over cellular signaling and affects cellular phenotype in an ex-vivo wound-healing model. Our approach for nanodelivery of functional membrane receptors expands the current toolkit for DNA and RNA-free manipulation of cellular function. We expect this approach to be readily applicable to the synthesis and nanodelivery of other types of GPCRs and membrane receptors, opening new doors for therapeutic development at the intersection between synthetic biology and nanomedicine.
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spelling doaj.art-d4115b454b4245c79e61e876075b33322022-12-21T21:51:46ZengNature PortfolioScientific Reports2045-23222018-02-018111110.1038/s41598-018-21863-3Nanodelivery of a functional membrane receptor to manipulate cellular phenotypeTommaso Patriarchi0Ao Shen1Wei He2Mo Baikoghli3R. Holland Cheng4Yang K. Xiang5Matthew A. Coleman6Lin Tian7University of California Davis, School of Medicine, Department of Biochemistry and Molecular MedicineUniversity of California Davis, School of Medicine, Department of PharmacologyLawrence Livermore National LaboratoryUniversity of California Davis, Department of Molecular and Cellular BiologyUniversity of California Davis, Department of Molecular and Cellular BiologyUniversity of California Davis, School of Medicine, Department of PharmacologyLawrence Livermore National LaboratoryUniversity of California Davis, School of Medicine, Department of Biochemistry and Molecular MedicineAbstract Modification of membrane receptor makeup is one of the most efficient ways to control input-output signals but is usually achieved by expressing DNA or RNA-encoded proteins or by using other genome-editing methods, which can be technically challenging and produce unwanted side effects. Here we develop and validate a nanodelivery approach to transfer in vitro synthesized, functional membrane receptors into the plasma membrane of living cells. Using β2-adrenergic receptor (β2AR), a prototypical G-protein coupled receptor, as an example, we demonstrated efficient incorporation of a full-length β2AR into a variety of mammalian cells, which imparts pharmacologic control over cellular signaling and affects cellular phenotype in an ex-vivo wound-healing model. Our approach for nanodelivery of functional membrane receptors expands the current toolkit for DNA and RNA-free manipulation of cellular function. We expect this approach to be readily applicable to the synthesis and nanodelivery of other types of GPCRs and membrane receptors, opening new doors for therapeutic development at the intersection between synthetic biology and nanomedicine.https://doi.org/10.1038/s41598-018-21863-3
spellingShingle Tommaso Patriarchi
Ao Shen
Wei He
Mo Baikoghli
R. Holland Cheng
Yang K. Xiang
Matthew A. Coleman
Lin Tian
Nanodelivery of a functional membrane receptor to manipulate cellular phenotype
Scientific Reports
title Nanodelivery of a functional membrane receptor to manipulate cellular phenotype
title_full Nanodelivery of a functional membrane receptor to manipulate cellular phenotype
title_fullStr Nanodelivery of a functional membrane receptor to manipulate cellular phenotype
title_full_unstemmed Nanodelivery of a functional membrane receptor to manipulate cellular phenotype
title_short Nanodelivery of a functional membrane receptor to manipulate cellular phenotype
title_sort nanodelivery of a functional membrane receptor to manipulate cellular phenotype
url https://doi.org/10.1038/s41598-018-21863-3
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