Quantitative and Multiplexed Fluorescence Lifetime Imaging of Intercellular Tensile Forces

Angew Chem Int Ed Engl. 2021 Jul 5;60(28):15548-15555. doi: 10.1002/anie.202103986. Epub 2021 Jun 10.

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.

Keywords: DNA probes; cadherin; epithelial-mesenchymal transition; fluorescence lifetime imaging; intercellular tensile force.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cadherins / chemistry*
  • DNA / chemistry*
  • Fluorescence*
  • Fluorescent Dyes / chemistry*
  • Humans
  • Intercellular Junctions
  • Optical Imaging*
  • Tensile Strength

Substances

  • Cadherins
  • Fluorescent Dyes
  • DNA