Matrix Rigidity-Dependent Regulation of Ca 2+ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

Tae Jin Kim, Lei Lei, Jihye Seong, Jung Soo Suh, Yoon Kwan Jang, Sang Hoon Jung, Jie Sun, Deok Ho Kim, Yingxiao Wang

Research output: Contribution to journalArticlepeer-review

Abstract

The dynamic regulation of signal transduction at plasma membrane microdomains remains poorly understood due to limitations in current experimental approaches. Genetically encoded biosensors based on fluorescent resonance energy transfer (FRET) can provide high spatiotemporal resolution for imaging cell signaling networks. Here, distinctive regulation of focal adhesion kinase (FAK) and Ca 2+ signals are visualized at different membrane microdomains by FRET using membrane-targeting biosensors. It is shown that rigidity-dependent FAK and Ca 2+ signals in human mesenchymal stem cells (hMSCs) are selectively activated at detergent-resistant membrane (DRM or rafts) microdomains during the cell–matrix adhesion process, with minimal activities at non-DRM domains. The rigidity-dependent Ca 2+ signal at the DRM microdomains is downregulated by either FAK inhibition or lipid raft disruption, suggesting that FAK and lipid raft integrity mediate the in situ Ca 2+ activation. It is further revealed that transient receptor potential subfamily M7 (TRPM7) participates in the mobilization of Ca 2+ signals within DRM regions. Thus, the findings provide insights into the underlying mechanisms that regulate Ca 2+ and FAK signals in hMSCs under different mechanical microenvironments.

Original languageEnglish (US)
Article number1801290
JournalAdvanced Science
Volume6
Issue number4
DOIs
StatePublished - Feb 20 2019
Externally publishedYes

Keywords

  • biosensors
  • calcium
  • focal adhesion kinase
  • live cell imaging
  • matrix rigidity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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