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Cells are physically contacting with each other. Direct and precise quantification of forces at cell–cell junctions is still challenging. Herein, we have developed a DNA-based ratiometric fluorescent probe, termed DNAMeter, to quantify intercellular tensile forces. These lipid-modified DNAMeters can spontaneously anchor onto live cell membranes. The DNAMeter consists of two self-assembled DNA hairpins of different force tolerance. Once the intercellular tension exceeds the force tolerance to unfold a DNA hairpin, a specific fluorescence signal will be activated, which enables the real-time imaging and quantification of tensile forces. Using E-cadherin-modified DNAMeter as an example, we have demonstrated an approach to quantify, at the molecular level, the magnitude and distribution of E-cadherin tension among epithelial cells. Compatible with readily accessible fluorescence microscopes, these easy-to-use DNA tension probes can be broadly used to quantify mechanotransduction in collective cell behaviors.
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Quantitative and Multiplexed Fluorescence Lifetime Imaging of Intercellular Tensile Forces
Abstract Mechanical interactions between cells have been shown to play critical roles in regulating cell signaling and communications. However, the precise measurement of intercellular forces is still quite challenging, especially considering the complex environment at cell–cell junctions. In this study, we report a fluorescence lifetime‐based approach to image and quantify intercellular molecular tensions. Using this method, tensile forces among multiple ligand–receptor pairs can be measured simultaneously. We first validated our approach and developed lifetime measurement‐based DNA tension probes to image E‐cadherin‐mediated tension on epithelial cells. These probes were then further applied to quantify the correlations between E‐cadherin and N‐cadherin tensions during an epithelial–mesenchymal transition process. The modular design of these probes can potentially be used to study the mechanical features of various physiological and pathological processes.
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- Award ID(s):
- 1846866
- PAR ID:
- 10249043
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 60
- Issue:
- 28
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 15548-15555
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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