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.
引用
收藏
页数:9
相关论文
共 49 条
  • [1] Mechanosensitive ion channels and their mode of activation
    Ghazi, A
    Berrier, C
    Ajouz, B
    Besnard, M
    BIOCHIMIE, 1998, 80 (5-6) : 357 - 362
  • [2] ACTIVATION OF MECHANOSENSITIVE ION CHANNELS BY ULTRASOUND
    Chu, Ya-Cherng
    Lim, Jormay
    Chien, Andy
    Chen, Chih-Cheng
    Wang, Jaw-Lin
    ULTRASOUND IN MEDICINE AND BIOLOGY, 2022, 48 (10): : 1981 - 1994
  • [3] Selective activation of mechanosensitive ion channels using magnetic particles
    Hughes, Steven
    McBain, Stuart
    Dobson, Jon
    El Haj, Alicia J.
    JOURNAL OF THE ROYAL SOCIETY INTERFACE, 2008, 5 (25) : 855 - 863
  • [4] Photo-activation of mechanosensitive ion channels
    Crea, F.
    Morstein, J.
    Heberle, J.
    Trauner, D.
    EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 2019, 48 : S173 - S173
  • [5] Magnetic micro- and nanoparticle mediated activation of mechanosensitive ion channels
    Hughes, S
    El Haj, AJ
    Dobson, J
    MEDICAL ENGINEERING & PHYSICS, 2005, 27 (09) : 754 - 762
  • [6] Activation of mechanosensitive ion channels by forces transmitted through integrins and the cytoskeleton
    Matthews, Benjamin D.
    Thodeti, Charles K.
    Ingber, Donald E.
    MECHANOSENSITIVE ION CHANNELS, PART A, 2007, 58 : 59 - 85
  • [7] Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets
    Kapsalis, Charalampos
    Wang, Bolin
    El Mkami, Hassane
    Pitt, Samantha J.
    Schnell, Jason R.
    Smith, Terry K.
    Lippiat, Jonathan D.
    Bode, Bela E.
    Pliotas, Christos
    NATURE COMMUNICATIONS, 2019, 10 (1)
  • [8] Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets
    Charalampos Kapsalis
    Bolin Wang
    Hassane El Mkami
    Samantha J. Pitt
    Jason R. Schnell
    Terry K. Smith
    Jonathan D. Lippiat
    Bela E. Bode
    Christos Pliotas
    Nature Communications, 10
  • [9] Dynamic ion channel activation scheduling in patch clamp on a chip
    Krishnamurthy, V
    IEEE TRANSACTIONS ON NANOBIOSCIENCE, 2004, 3 (03) : 217 - 224
  • [10] Activation of the mechanosensitive ion channel MscL by mechanical stimulation of supported Droplet-Hydrogel bilayers
    Rosholm, Kadla R.
    Baker, Matthew A. B.
    Ridone, Pietro
    Nakayama, Yoshitaka
    Rohde, Paul R.
    Cuello, Luis G.
    Lee, Lawrence K.
    Martinac, Boris
    SCIENTIFIC REPORTS, 2017, 7