Mechanically Triggered Hybridization Chain Reaction.

Area of Science:

• Biophysics
• Molecular Biology
• Cell Biology

Background:

• Cells exert piconewton forces on receptors, crucial for processes like migration and immune recognition.
• Quantifying these cellular forces is challenging due to the sparse nature of mechanical events.
• Current methods like fluorescence microscopy require high resolution, limiting accessibility.

Purpose of the Study:

• To develop a novel method for amplifying and quantifying cellular mechanical events.
• To enable direct readout of piconewton forces using accessible plate reader technology.
• To facilitate drug discovery and personalized medicine by assessing cell mechanical phenotypes.

Main Methods:

• Developed a mechanically triggered hybridization chain reaction (mechano-HCR) assay.
• Mechano-HCR uses mechanical force to denature a duplex, exposing an initiator to trigger a chemical amplification reaction (HCR) in situ.
• Utilized a plate reader for direct quantification of pN forces.

Main Results:

• Successfully demonstrated chemical amplification of mechanical events via mechano-HCR.
• Enabled direct, high-throughput readout of pN forces using a standard plate reader.
• Measured mechanical inhibitory concentrations (mechano-IC50) for aspirin, Y-27632, and eptifibatide.

Conclusions:

• Mechano-HCR provides a convenient and accessible method for quantifying cellular forces.
• This technology has significant potential for drug discovery, personalized medicine, and disease diagnosis.
• Assessing cell mechanical phenotypes can be streamlined for clinical applications.