DNA-Based Microparticle Tension Sensors (μTS) for Measuring Cell Mechanics in Non-planar Geometries and for...

Area of Science:

• Biophysics
• Cell Biology
• Biotechnology

Background:

• Mechanotransduction, the link between physical and chemical signals, is crucial in biology.
• Current cell force quantification methods use planar substrates, limiting research scope and throughput.
• Microscopy-based readouts are low-throughput, hindering fundamental and clinical applications.

Purpose of the Study:

• To develop a novel, high-throughput method for measuring cellular forces at curved interfaces.
• To enable investigation of mechanotransduction beyond planar geometries.
• To demonstrate the utility of the new sensor in drug screening.

Main Methods:

• Development of a DNA-based microparticle tension sensor (μTS) with a spherical geometry.
• Utilizing flow cytometry for rapid, high-throughput readout of μTS measurements.
• Application of μTS to measure T-cell receptor and platelet integrin forces.
• Quantification of anti-platelet drug efficacy using the μTS.

Main Results:

• The spherical μTS allows mechanotransduction studies at curved interfaces.
• Flow cytometry readout provides rapid and high-throughput analysis.
• Successfully mapped and measured T-cell receptor and platelet integrin forces at specific thresholds (12 and 56 pN).
• Demonstrated proof-of-concept for drug screening by quantifying inhibition efficiency of anti-platelet agents.

Conclusions:

• The DNA-based microparticle tension sensor offers a versatile and high-throughput platform for cell force quantification.
• This technology expands the study of mechanotransduction to curved biological interfaces.
• The μTS serves as a valuable tool for drug discovery targeting cellular mechanics.