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

被引:1
|
作者
Unnithan, Afeesh Rajan [1 ,2 ]
Rotherham, Michael [1 ]
Markides, Hareklea [1 ]
El Haj, Alicia J. [1 ]
机构
[1] Univ Birmingham, Healthcare Technol Inst, Inst Translat Med, Birmingham B15 2TH, England
[2] Univ Bradford, Fac Lifesciences, Ctr Pharmaceut Engn Sci, Sch Pharm & Med Sci, Bradford BD7 1DP, England
基金
欧洲研究理事会;
关键词
magnetic nanoparticles; mechanosensitive ion channels; mechano-transduction; calcium assay; drug screening; nanomedicine; DRUG-DELIVERY; NANOPARTICLES; PARTICLE; PROTEIN; TREK-1;
D O I
10.3390/ijms24043364
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页数:9
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