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

Afeesh Rajan Unnithan*, Michael Rotherham, Hareklea Markides, Alicia J. El haj

*Corresponding author for this work

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Abstract

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 Ca2+ 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.
Original languageEnglish
Article number3364
Number of pages9
JournalInternational Journal of Molecular Sciences
Volume24
Issue number4
DOIs
Publication statusPublished - 8 Feb 2023

Keywords

  • magnetic nanoparticles
  • mechanosensitive ion channels
  • mechano-transduction
  • calcium assay
  • drug screening
  • nanomedicine
  • Communication

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