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Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels

This study reports results of a mechanical platform-based screening assay (MICA) to evaluate the remote activation of mechanosensitive ion channels. Here, we studied ERK pathway activation and the elevation in intracellular Ca(2+) levels in response to the MICA application using the Luciferase assay...

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Detalles Bibliográficos
Autores principales: Unnithan, Afeesh Rajan, Rotherham, Michael, Markides, Hareklea, El Haj, Alicia J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962865/
https://www.ncbi.nlm.nih.gov/pubmed/36834776
http://dx.doi.org/10.3390/ijms24043364
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author Unnithan, Afeesh Rajan
Rotherham, Michael
Markides, Hareklea
El Haj, Alicia J.
author_facet Unnithan, Afeesh Rajan
Rotherham, Michael
Markides, Hareklea
El Haj, Alicia J.
author_sort Unnithan, Afeesh Rajan
collection PubMed
description This study reports results of a mechanical platform-based screening assay (MICA) to evaluate the remote activation of mechanosensitive ion channels. Here, we studied ERK pathway activation and the elevation in intracellular Ca(2+) levels in response to the MICA application using the Luciferase assay and Fluo-8AM assay, respectively. Functionalised magnetic nanoparticles (MNPs) targeting membrane-bound integrins and mechanosensitive TREK1 ion channels were studied with HEK293 cell lines under MICA application. The study demonstrated that active targeting of mechanosensitive integrins via RGD (Arginylglycylaspartic acid) motifs or TREK1 (KCNK2, potassium channel subfamily K member 2) ion channels can stimulate the ERK pathway and intracellular calcium levels compared to non-MICA controls. This screening assay offers a powerful tool, which aligns with existing high-throughput drug screening platforms for use in the assessment of drugs that interact with ion channels and influence ion channel-modulated diseases.
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spelling pubmed-99628652023-02-26 Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels Unnithan, Afeesh Rajan Rotherham, Michael Markides, Hareklea El Haj, Alicia J. Int J Mol Sci Communication This study reports results of a mechanical platform-based screening assay (MICA) to evaluate the remote activation of mechanosensitive ion channels. Here, we studied ERK pathway activation and the elevation in intracellular Ca(2+) levels in response to the MICA application using the Luciferase assay and Fluo-8AM assay, respectively. Functionalised magnetic nanoparticles (MNPs) targeting membrane-bound integrins and mechanosensitive TREK1 ion channels were studied with HEK293 cell lines under MICA application. The study demonstrated that active targeting of mechanosensitive integrins via RGD (Arginylglycylaspartic acid) motifs or TREK1 (KCNK2, potassium channel subfamily K member 2) ion channels can stimulate the ERK pathway and intracellular calcium levels compared to non-MICA controls. This screening assay offers a powerful tool, which aligns with existing high-throughput drug screening platforms for use in the assessment of drugs that interact with ion channels and influence ion channel-modulated diseases. MDPI 2023-02-08 /pmc/articles/PMC9962865/ /pubmed/36834776 http://dx.doi.org/10.3390/ijms24043364 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Unnithan, Afeesh Rajan
Rotherham, Michael
Markides, Hareklea
El Haj, Alicia J.
Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels
title Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels
title_full Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels
title_fullStr Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels
title_full_unstemmed Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels
title_short Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels
title_sort magnetic ion channel activation (mica)-enabled screening assay: a dynamic platform for remote activation of mechanosensitive ion channels
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962865/
https://www.ncbi.nlm.nih.gov/pubmed/36834776
http://dx.doi.org/10.3390/ijms24043364
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