On Vibronic-Driven Action and Mechanosensitive G Protein-Coupled Receptors

Area of Science:

• Biochemistry and Molecular Biology
• Cell Signaling
• Nanotechnology

Background:

• G protein-coupled receptors (GPCRs) are crucial drug targets, but ligand-independent activation is common.
• Calcium signaling is a fundamental cellular process often mediated by GPCRs.
• Existing methods for GPCR activation include agonist stimulation, nanoclustering, and photodynamic approaches.

Purpose of the Study:

• To investigate a novel method for activating Gq-mediated calcium signaling.
• To explore the potential of cyanine-based plasmonic molecules as activators of cellular signaling.
• To compare this new activation mechanism with known GPCR-related signaling pathways.

Main Methods:

• Insertion of cyanine skeleton-based plasmonic molecules (molecular jackhammers) into the plasma membrane.
• Excitation of these molecules using far-red light (730 nm).
• Monitoring of Gq-mediated calcium signaling in epithelial and muscle cell lines.

Main Results:

• Vibronically-driven activation of Gq-mediated calcium signaling was observed in four different cell lines.
• This activation occurred independently of traditional agonist stimulation of Gq-coupled GPCRs.
• The novel activation mechanism was compared to nanoclustering of the neuropeptide Y2 receptor and photodynamic activation of cholecystokinin receptors.

Conclusions:

• Cyanine-based plasmonic molecules can induce Gq-mediated calcium signaling through a novel vibronic mechanism.
• This ligand-independent activation pathway offers a new tool for modulating cellular calcium signaling.
• Further research is needed to elucidate the precise role and involvement of GPCRs in this phenomenon.