Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell
Abstract Interface between neuron cells and biomaterials is the key to real-time sensing, transmitting and manipulating of neuron activities, which are the long-term pursue of scientists and gain intense research focus recently. It is of great interest to develop a sensor with exquisite sensitivity...
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doaj-627c9ae2d1a34089a0d9bfcc895be38a2021-04-02T20:45:30ZengSpringerMolecular Biomedicine2662-86512021-02-01211910.1186/s43556-021-00026-3Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cellXialin Zhang0Linqin Dou1Ming Zhang2Yu Wang3Xin Jiang4Xinqiong Li5Long Wei6Yuejia Chen7Cuisong Zhou8Jia Geng9Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterCollege of Chemistry, Sichuan UniversityDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation CenterAbstract Interface between neuron cells and biomaterials is the key to real-time sensing, transmitting and manipulating of neuron activities, which are the long-term pursue of scientists and gain intense research focus recently. It is of great interest to develop a sensor with exquisite sensitivity and excellent selectivity for real-time monitoring neurotransmitters transport through single live cell. Sensing techniques including electrode-based methods, optogenetics, and nanowire cell penetration systems have been developed to monitor the neuron activities. However, their biocompatibilities remain a challenge. Protein nanopores with membrane compatibility and lumen tunability provide real-time, single-molecule sensitivities for biosensing of DNA, RNA, peptides and small molecules. In this study, an engineered protein nanopore MspA (Mycobacterium smegmatis porin A) through site-directed mutation with histidine selectively bind with Cu2+ in its internal lumen. Chelation of neurotransmitters such as L-glutamate (L-Glu), dopamine (DA) and norepinephrine (NE) with the Cu2+ creates specific current signals, showing different transient current blockade and dwell time in single channel electrophysiological recording. Furthermore, the functionalized M2MspA-N91H nanopores have been embedded in live HEK293T cell membrane for real-time, in situ monitoring of extracellular L-glutamate translocating through the nanopore. This biomimetic neurotransmitter nanopore has provided a new platform for future development of neuron sensors, drug carrier and artificial synapse.https://doi.org/10.1186/s43556-021-00026-3NanoporeNeurotransmitter detectionArtificial synapseBiosensor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xialin Zhang Linqin Dou Ming Zhang Yu Wang Xin Jiang Xinqiong Li Long Wei Yuejia Chen Cuisong Zhou Jia Geng |
spellingShingle |
Xialin Zhang Linqin Dou Ming Zhang Yu Wang Xin Jiang Xinqiong Li Long Wei Yuejia Chen Cuisong Zhou Jia Geng Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell Molecular Biomedicine Nanopore Neurotransmitter detection Artificial synapse Biosensor |
author_facet |
Xialin Zhang Linqin Dou Ming Zhang Yu Wang Xin Jiang Xinqiong Li Long Wei Yuejia Chen Cuisong Zhou Jia Geng |
author_sort |
Xialin Zhang |
title |
Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell |
title_short |
Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell |
title_full |
Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell |
title_fullStr |
Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell |
title_full_unstemmed |
Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell |
title_sort |
real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell |
publisher |
Springer |
series |
Molecular Biomedicine |
issn |
2662-8651 |
publishDate |
2021-02-01 |
description |
Abstract Interface between neuron cells and biomaterials is the key to real-time sensing, transmitting and manipulating of neuron activities, which are the long-term pursue of scientists and gain intense research focus recently. It is of great interest to develop a sensor with exquisite sensitivity and excellent selectivity for real-time monitoring neurotransmitters transport through single live cell. Sensing techniques including electrode-based methods, optogenetics, and nanowire cell penetration systems have been developed to monitor the neuron activities. However, their biocompatibilities remain a challenge. Protein nanopores with membrane compatibility and lumen tunability provide real-time, single-molecule sensitivities for biosensing of DNA, RNA, peptides and small molecules. In this study, an engineered protein nanopore MspA (Mycobacterium smegmatis porin A) through site-directed mutation with histidine selectively bind with Cu2+ in its internal lumen. Chelation of neurotransmitters such as L-glutamate (L-Glu), dopamine (DA) and norepinephrine (NE) with the Cu2+ creates specific current signals, showing different transient current blockade and dwell time in single channel electrophysiological recording. Furthermore, the functionalized M2MspA-N91H nanopores have been embedded in live HEK293T cell membrane for real-time, in situ monitoring of extracellular L-glutamate translocating through the nanopore. This biomimetic neurotransmitter nanopore has provided a new platform for future development of neuron sensors, drug carrier and artificial synapse. |
topic |
Nanopore Neurotransmitter detection Artificial synapse Biosensor |
url |
https://doi.org/10.1186/s43556-021-00026-3 |
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