Quantitative and Multiplexed Fluorescence Lifetime Imaging of Intercellular Tensile Forces

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.

Automated summary

Fluorescence lifetime-based imaging and quantification of intercellular molecular tensions offer a novel approach to simultaneously measure tensile forces among multiple ligand-receptor pairs. This method was validated and DNA tension probes were developed for imaging E-cadherin-mediated tension, which were 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 has the potential to study the mechanical features of various physiological and pathological processes.