Application

Mechanically induced catalytic amplification reaction (MCR) as an assay for high throughput screening of drugs which target cellular mechanics and mechanical phenotyping of live cells.

Key Benefits

• Adaptable for high throughput screening of drugs that impair cell mechanics.
• Enables characterization of different cells types based on their traction forces.
• Assay can be performed using a conventional fluorescence plate reader.
• Allows detection of weak and transient cellular forces.

Market Summary

High Throughput Screening (HTS) is a drug-discovery process widely used in the pharmaceutical industry. It leverages automation to quickly assay the biological or biochemical activity of a large number of drug-like compounds. HTS of drugs that target mechanical processes and screening the mechanical phenotype of a library of cells is expensive and challenging. Current assays for the measurement and quantification of receptor-mediated forces in cells require high-end microscopy systems which are less affordable in general molecular biology labs. Therefore, there is a pressing need to develop strategies and toolkits that can easily translate receptor-mediated forces into an easily quantifiable and amplified chemical signal to allow rapid drug screening.

Technical Summary

Emory inventors have developed a low cost and quick assay to measure receptor mediated forces using mechanically induced catalytic amplification reaction (MCR). The assay is akin to PCR or ELISA for cell traction forces. The assay involves use of labile DNA duplexes with ligands that are immobilized on surfaces. Mechanical force acting on a ligand via its cognate receptor denatures the duplex thereby exposing a blocked primer. Amplification of primers is achieved using an isothermal polymerization reaction and quantified by fluorescence readout. This unique technology can be used to rapidly quantify cell traction forces using a conventional fluorescence plate reader. The researchers have demonstrated screening of a small library of antibodies and small molecules that inhibit cell traction forces across different cell types. The assay can be easily used to characterize cell tumor subtypes and elucidate the differences in their traction stresses. The catalytic amplification of signal allows detection of weak and transient mechanical forces which are otherwise difficult to quantify. MCR may also serve as a powerful tool for high throughput screening of drugs that target cellular mechanics.

Development Stage

Proof of concept has been demonstrated in a laboratory setting.

Publication: VP Ma et al., (2016). Angew Chem Int Ed Engl. 55(18):5488-92.