Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway

Cyclic adenosine monophosphate (cAMP) is an important research target because it activates protein kinases, and its signaling pathway regulates the passage of ions and molecules inside a cell. To detect the chemical reactions related to the cAMP intracellular signaling pathway, cAMP, adenosine triph...

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Main Authors: Yuki Komoto, Takahito Ohshiro, Masateru Taniguchi
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/11/3/784
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author Yuki Komoto
Takahito Ohshiro
Masateru Taniguchi
author_facet Yuki Komoto
Takahito Ohshiro
Masateru Taniguchi
author_sort Yuki Komoto
collection DOAJ
description Cyclic adenosine monophosphate (cAMP) is an important research target because it activates protein kinases, and its signaling pathway regulates the passage of ions and molecules inside a cell. To detect the chemical reactions related to the cAMP intracellular signaling pathway, cAMP, adenosine triphosphate (ATP), adenosine monophosphate (AMP), and adenosine diphosphate (ADP) should be selectively detected. This study utilized single-molecule quantum measurements of these adenosine family molecules to detect their individual electrical conductance using nanogap devices. As a result, cAMP was electrically detected at the single molecular level, and its signal was successfully discriminated from those of ATP, AMP, and ADP using the developed machine learning method. The discrimination accuracies of a single cAMP signal from AMP, ADP, and ATP were found to be 0.82, 0.70, and 0.72, respectively. These values indicated a 99.9% accuracy when detecting more than ten signals. Based on an analysis of the feature values used for the machine learning analysis, it is suggested that this discrimination was due to the structural difference between the ribose of the phosphate site of cAMP and those of ATP, ADP, and AMP. This method will be of assistance in detecting and understanding the intercellular signaling pathways for small molecular second messengers.
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spelling doaj.art-b8b3c569ee0b4ef79173f52696f70de82023-11-21T11:08:19ZengMDPI AGNanomaterials2079-49912021-03-0111378410.3390/nano11030784Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling PathwayYuki Komoto0Takahito Ohshiro1Masateru Taniguchi2Institute of Science and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, JapanInstitute of Science and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, JapanInstitute of Science and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, JapanCyclic adenosine monophosphate (cAMP) is an important research target because it activates protein kinases, and its signaling pathway regulates the passage of ions and molecules inside a cell. To detect the chemical reactions related to the cAMP intracellular signaling pathway, cAMP, adenosine triphosphate (ATP), adenosine monophosphate (AMP), and adenosine diphosphate (ADP) should be selectively detected. This study utilized single-molecule quantum measurements of these adenosine family molecules to detect their individual electrical conductance using nanogap devices. As a result, cAMP was electrically detected at the single molecular level, and its signal was successfully discriminated from those of ATP, AMP, and ADP using the developed machine learning method. The discrimination accuracies of a single cAMP signal from AMP, ADP, and ATP were found to be 0.82, 0.70, and 0.72, respectively. These values indicated a 99.9% accuracy when detecting more than ten signals. Based on an analysis of the feature values used for the machine learning analysis, it is suggested that this discrimination was due to the structural difference between the ribose of the phosphate site of cAMP and those of ATP, ADP, and AMP. This method will be of assistance in detecting and understanding the intercellular signaling pathways for small molecular second messengers.https://www.mdpi.com/2079-4991/11/3/784DNAcyclic AMPsingle-molecule detectionnanogapsecond messenger
spellingShingle Yuki Komoto
Takahito Ohshiro
Masateru Taniguchi
Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway
Nanomaterials
DNA
cyclic AMP
single-molecule detection
nanogap
second messenger
title Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway
title_full Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway
title_fullStr Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway
title_full_unstemmed Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway
title_short Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway
title_sort development of single molecule electrical identification method for cyclic adenosine monophosphate signaling pathway
topic DNA
cyclic AMP
single-molecule detection
nanogap
second messenger
url https://www.mdpi.com/2079-4991/11/3/784
work_keys_str_mv AT yukikomoto developmentofsinglemoleculeelectricalidentificationmethodforcyclicadenosinemonophosphatesignalingpathway
AT takahitoohshiro developmentofsinglemoleculeelectricalidentificationmethodforcyclicadenosinemonophosphatesignalingpathway
AT masaterutaniguchi developmentofsinglemoleculeelectricalidentificationmethodforcyclicadenosinemonophosphatesignalingpathway