Defining single molecular forces required to activate integrin and notch signaling

Science. 2013 May 24;340(6135):991-4. doi: 10.1126/science.1231041.


Cell-cell and cell-matrix mechanical interactions through membrane receptors direct a wide range of cellular functions and orchestrate the development of multicellular organisms. To define the single molecular forces required to activate signaling through a ligand-receptor bond, we developed the tension gauge tether (TGT) approach in which the ligand is immobilized to a surface through a rupturable tether before receptor engagement. TGT serves as an autonomous gauge to restrict the receptor-ligand tension. Using a range of tethers with tunable tension tolerances, we show that cells apply a universal peak tension of about 40 piconewtons (pN) to single integrin-ligand bonds during initial adhesion. We find that less than 12 pN is required to activate Notch receptors. TGT can also provide a defined molecular mechanical cue to regulate cellular functions.

Publication types

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

MeSH terms

  • Animals
  • CHO Cells
  • Cell Adhesion
  • Cell Communication*
  • Cricetinae
  • Cricetulus
  • DNA / chemistry
  • HEK293 Cells
  • Humans
  • Integrins / agonists*
  • Ligands
  • Mechanotransduction, Cellular*
  • Mice
  • NIH 3T3 Cells
  • Receptors, Notch / agonists*
  • Shear Strength
  • Surface Properties


  • Integrins
  • Ligands
  • Receptors, Notch
  • DNA