Photocleavable Cadherin Inhibits Cell-to-Cell Mechanotransduction by Light

ACS Chem Biol. 2019 Oct 18;14(10):2206-2214. doi: 10.1021/acschembio.9b00460. Epub 2019 Sep 20.

Abstract

Precise integration of individual cell behaviors is indispensable for collective tissue morphogenesis and maintenance of tissue integrity. Organized multicellular behavior is achieved via mechanical coupling of individual cellular contractility, mediated by cell adhesion molecules at the cell-cell interface. Conventionally, gene depletion or laser microsurgery has been used for functional analysis of intercellular mechanotransduction. Nevertheless, these methods are insufficient to investigate either the spatiotemporal dynamics or the biomolecular contribution in cell-cell mechanical coupling within collective multicellular behaviors. Herein, we present our effort in adaption of PhoCl for attenuation of cell-to-cell tension transmission mediated by E-cadherin. To release intercellular contractile tension applied on E-cadherin molecules with external light, a genetically encoded photocleavable module called PhoCl was inserted into the intracellular domain of E-cadherin, thereby creating photocleavable cadherin (PC-cadherin). In response to light illumination, the PC-cadherin cleaved into two fragments inside cells, resulting in attenuating mechanotransduction at intercellular junctions in living epithelial cells. Light-induced perturbation of the intercellular tension balance with surrounding cells changed the cell shape in an epithelial cell sheet. The method is expected to enable optical manipulation of force-mediated cell-to-cell communications in various multicellular behaviors, which contributes to a deeper understanding of embryogenesis and oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Actomyosin / metabolism
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Antigens, CD / radiation effects
  • Cadherins / immunology
  • Cadherins / metabolism*
  • Cadherins / radiation effects
  • Cell Communication
  • Dogs
  • Epithelial Cells / cytology
  • Fluorescence
  • Humans
  • Light
  • Luminescent Proteins / metabolism
  • Luminescent Proteins / radiation effects
  • MCF-7 Cells
  • Madin Darby Canine Kidney Cells
  • Mechanotransduction, Cellular / radiation effects*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Recombinant Fusion Proteins / metabolism*
  • Recombinant Fusion Proteins / radiation effects
  • Red Fluorescent Protein

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Luminescent Proteins
  • Recombinant Fusion Proteins
  • Actomyosin